[ { "id": "5-amino-1mq", "name": "5-Amino-1MQ", "aliases": [ "5-Amino-1-methylquinolinium", "5A1MQ", "5-amino-1-methylquinoline" ], "tier": "stub", "category": "metabolic", "subcategory": "NNMT inhibitor (small molecule)", "class": "Note: 5-Amino-1MQ is a small-molecule nicotinamide-N-methyltransferase (NNMT) inhibitor based on a methylquinolinium scaffold, not a peptide. It is included here because it is universally grouped with peptide therapeutics in fat-loss and longevity biohacker protocols.", "tagline": "A small-molecule NNMT inhibitor studied in preclinical obesity models for its ability to raise intracellular NAD+ and suppress lipogenesis, with no published human trials as of 2026.", "oneLiner": "An experimental NNMT inhibitor that raises intracellular NAD+ and SAM and reduces adipocyte fat storage in rodent models; commonly sold alongside peptide stacks for fat loss despite the absence of human safety or efficacy data.", "sequence": "Not applicable — 5-Amino-1MQ is a small molecule based on a 1-methylquinolinium scaffold with an amine substitution at the 5-position.", "molecularFormula": "C10H11N2+", "molecularWeight": 159.21, "halfLife": { "value": null, "unit": null, "range": "undetermined in humans", "notes": "Rodent PK data indicate reasonable oral bioavailability and CNS penetrance; human pharmacokinetics are not published." }, "fdaStatus": "research-only", "approvalDetails": "Not approved by any regulatory agency for any indication. Sold exclusively as a research chemical. No IND filings or clinical trials registered with ClinicalTrials.gov as of early 2026.", "mechanism": "Selectively inhibits nicotinamide-N-methyltransferase (NNMT), an enzyme elevated in adipose tissue of obese individuals that catalyzes the methylation of nicotinamide using S-adenosyl methionine (SAM). NNMT inhibition preserves intracellular NAD+ and SAM pools, suppresses lipogenic transcription factors (PPARγ, C/EBPα, SREBP1), reduces triglyceride accumulation in adipocytes, and may upregulate adiponectin. In rodent studies, it has reduced body weight, adipocyte size, and liver adiposity without affecting food intake.", "primaryUses": [ "Experimental fat loss protocols (preclinical rodent data only)", "Biohacker stacks for metabolic health (off-label, unstudied in humans)", "Research tool for NNMT pathway investigation" ], "typicalDose": { "range": "50–150", "unit": "mg", "frequency": "1x daily", "route": "oral (capsule)", "notes": "Community dosing extrapolated from rodent studies; no human dose has been established through clinical research. Typically taken in cycles of 4–8 weeks." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Neelakantan H, et al. \"Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high fat diet-induced obesity in mice.\" Biochem Pharmacol, 2018;147:141-152. PMID: 29155147.", "pmid": "29155147" }, { "type": "review", "citation": "Liu M, Li L, Chu J, et al. \"Roles of nicotinamide N-methyltransferase in obesity and type 2 diabetes.\" Biomed Res Int, 2021;2021:9924314. PMID: 34368359.", "pmid": "34368359" }, { "type": "pubmed", "citation": "Kannt A, et al. \"A small molecule inhibitor of nicotinamide N-methyltransferase for the treatment of metabolic disorders.\" Sci Rep, 2018;8(1):3660. PMID: 29483571.", "pmid": "29483571" } ], "interactionCoverage": "partial", "related": [ "nad-plus", "mots-c", "tesofensine" ], "lastReviewed": "2026-04-20", "publishedAt": "2026-04-20", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "small-molecule", "moleculeClassBasis": "small-molecule" }, { "id": "abarelix", "name": "Abarelix", "aliases": [ "Plenaxis", "R-3827" ], "tier": "stub", "category": "sexual-health", "subcategory": "GnRH antagonist (injectable)", "class": "A synthetic decapeptide GnRH antagonist, the first injectable GnRH antagonist approved for prostate cancer in the US (subsequently withdrawn).", "tagline": "The first injectable GnRH antagonist for prostate cancer — a synthetic decapeptide that achieved castration without testosterone flare, later supplanted by degarelix and oral alternatives.", "oneLiner": "A synthetic decapeptide GnRH receptor antagonist that was the first in its class approved for prostate cancer (2003), achieving immediate testosterone suppression without the agonist flare of leuprolide, but withdrawn from the US market due to anaphylaxis risk.", "sequence": "D-Ala-D-Phe(4-Cl)-D-Ala-Ser-Tyr-D-Asn-Leu-Lys(iPr)-Pro-D-Ala-NH2", "molecularFormula": "C72H95ClN14O14", "molecularWeight": 1416.1, "halfLife": { "value": 13, "unit": "days", "range": "~13 days", "notes": "Depot formulation. Long duration allowed monthly intramuscular injection." }, "fdaStatus": "withdrawn", "approvalDetails": "FDA-approved in 2003 (Plenaxis, Praecis) for symptomatic advanced prostate cancer under restricted distribution. Voluntarily withdrawn from the US market in 2005 due to systemic allergic reactions. Still available in some markets.", "mechanism": "Competitive antagonist at the GnRH receptor on pituitary gonadotrophs. Immediately suppresses LH and FSH release, achieving castrate testosterone without the initial surge (flare) that occurs with GnRH agonists. Histamine release from the formulation was responsible for the anaphylactic reactions that led to withdrawal.", "primaryUses": [ "Advanced prostate cancer (historical)", "Androgen deprivation therapy" ], "typicalDose": { "range": "100", "unit": "mg", "frequency": "intramuscular, days 1, 15, 29, then every 4 weeks", "route": "intramuscular", "notes": "US-withdrawn. Superseded by degarelix (Firmagon) and relugolix (Orgovyx)." }, "evidenceLevel": "high", "sources": [ { "type": "clinical-trial", "citation": "Trachtenberg J, et al. \"A phase 3, multicenter, open label, randomized study of abarelix versus leuprolide plus daily antiandrogen in men with prostate cancer.\" J Urol, 2002;167:1670-1674. PMID: 11912385.", "pmid": "11912385" } ], "interactionCoverage": "unreviewed", "related": [ "degarelix", "relugolix", "leuprolide", "goserelin" ], "lastReviewed": "2026-04-20", "publishedAt": "2026-04-20", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Withdrawn from the US market in 2005; our entry notes it is still sold in some markets, which we have not verified. A GnRH antagonist: S2.2.1 covers GnRH and its agonist analogues, not antagonists." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Withdrawn from the US market in 2005; our entry notes it is still sold in some markets, which we have not verified. A GnRH antagonist: S2.2.1 covers GnRH and its agonist analogues, not antagonists." } ], "moleculeClass": "peptide" }, { "id": "ace-031", "name": "ACE-031", "aliases": [ "Ramatercept", "ActRIIB-Fc", "Activin type IIB receptor-Fc fusion" ], "tier": "stub", "category": "research", "subcategory": "activin receptor decoy (myostatin inhibitor)", "class": "A soluble activin type IIB receptor-Fc fusion protein that acts as a ligand trap for myostatin and related activin/TGF-β family members.", "tagline": "Acceleron's first-generation myostatin trap — Phase 2 development in Duchenne muscular dystrophy was halted in 2013 after epistaxis and telangiectasia adverse events, but the same scaffold concept led to successor programs at Acceleron, Regeneron, and Lilly.", "oneLiner": "A recombinant fusion protein combining the extracellular ligand-binding domain of activin receptor type IIB (ActRIIB) with a human IgG1 Fc, engineered by Acceleron Pharma to act as a circulating decoy that traps myostatin and related activin/TGF-β family ligands before they can activate endogenous ActRIIB on muscle.", "sequence": null, "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": null, "range": "Fc-mediated, typically 1–3 weeks in humans", "notes": "The Fc fusion architecture provides a long half-life typical of therapeutic antibodies, supporting monthly or less frequent dosing." }, "fdaStatus": "discontinued", "approvalDetails": "Not approved. Phase 2 development in Duchenne muscular dystrophy was suspended by Acceleron in April 2013 after two boys in the trial developed epistaxis and gum bleeding, with telangiectasias observed on examination — adverse events attributed to off-target inhibition of BMP9/BMP10 signaling (critical for vascular integrity). Acceleron pivoted to the more selective successor bimagrumab/luspatercept family.", "mechanism": "Acts as a soluble ligand trap: the extracellular ActRIIB domain binds myostatin, activin A, activin B, GDF-11, and — problematically — BMP9 and BMP10, sequestering them from their membrane receptors. Myostatin blockade drives muscle hypertrophy; BMP9/10 blockade appears to cause the vascular side effects that stopped development.", "primaryUses": [ "Historical: Duchenne muscular dystrophy (suspended)", "Precursor molecule for understanding activin-Fc decoy pharmacology", "Not in current community use due to discontinued development" ], "typicalDose": { "range": "discontinued", "unit": "", "frequency": "historical: monthly SC", "route": "subcutaneous", "notes": "Phase 2 DMD trial dosed 1–3 mg/kg SC monthly before suspension." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "Attie KM, et al. \"A single ascending-dose study of muscle regulator ACE-031 in healthy volunteers.\" Muscle Nerve, 2013;47:416-423. PMID: 23169607.", "pmid": "23169607" }, { "type": "news-release", "citation": "Acceleron Pharma. \"Acceleron suspends ACE-031 clinical development program in Duchenne muscular dystrophy.\" Press release, April 2013." } ], "interactionCoverage": "none-found", "related": [ "follistatin-344", "follistatin-315", "bimagrumab" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S4.3", "named": true, "wording": "Decoy activin receptors (e.g. ACE-031)", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S4.3", "named": true, "wording": "Decoy activin receptors (e.g. ACE-031)", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "protein", "moleculeClassBasis": "fusion protein" }, { "id": "acetyl-hexapeptide-30", "name": "Acetyl Hexapeptide-30", "aliases": [ "Inyline", "Acetyl Hexapeptide-25 (former INCI)" ], "tier": "stub", "category": "cosmetic", "subcategory": "topical cosmetic peptide (post-synaptic MuSK antagonist)", "class": "A synthetic acetylated hexapeptide marketed as a topical cosmetic ingredient with a post-synaptic neuromuscular mechanism — claimed competitive antagonist of agrin at the muscle-specific kinase (MuSK) binding site.", "tagline": "Inyline — Lipotec's post-synaptic cosmetic peptide. Unlike Argireline-family pre-synaptic SNAP-25 mimetics or Vialox-style nAChR antagonists, Acetyl Hexapeptide-30 is claimed to block the agrin-MuSK interaction that maintains post-synaptic AChR clustering; was formerly INCI Acetyl Hexapeptide-25.", "oneLiner": "A synthetic acetylated hexapeptide developed by Lipotec (now Lubrizol) under the trade name Inyline® and later repositioned as Syntides™. The ingredient was originally registered as INCI Acetyl Hexapeptide-25; the INCI designation was subsequently updated to Acetyl Hexapeptide-30 (the two terms refer to the same Lipotec active). Mechanism is proposed as competitive antagonism of agrin at the muscle-specific kinase (MuSK) binding site on the post-synaptic membrane. This post-synaptic mechanism is distinct from the pre-synaptic SNAP-25 competitive inhibition of Argireline/SNAP-8 and from the nAChR antagonism of Vialox. Sequence and molecular formula are treated as proprietary by Lipotec. Cosmetic ingredient only; not a drug.", "sequence": "Proprietary acetylated hexapeptide — specific sequence not disclosed by manufacturer", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": null, "range": "topical only", "notes": "Systemic absorption from topical cosmetic formulations is minimal." }, "fdaStatus": "research-only", "approvalDetails": "Cosmetic ingredient; not a drug. Current INCI name: Acetyl Hexapeptide-30 (formerly Acetyl Hexapeptide-25).", "mechanism": "Proposed as a competitive antagonist of agrin at its binding site on muscle-specific kinase (MuSK), a transmembrane receptor tyrosine kinase on the post-synaptic membrane of the neuromuscular junction. In normal physiology, motor-neuron-secreted agrin binds MuSK via the LRP4 co-receptor, triggering MuSK autophosphorylation and downstream clustering of acetylcholine receptors at the post-synaptic membrane. Blocking this interaction is proposed to reduce post-synaptic responsiveness to acetylcholine and thereby reduce expression-muscle contractions. This mechanism sits alongside — and is marketed as complementary to — the pre-synaptic SNAP-25 inhibition of Argireline-class peptides and the nAChR antagonism of Vialox. Independent mechanistic replication outside Lipotec is minimal.", "primaryUses": [ "Topical cosmetic anti-aging formulations (expression-line reduction — post-synaptic mechanism)" ], "typicalDose": { "range": "2–5", "unit": "% (finished formulation, as supplied Inyline solution)", "frequency": "twice daily", "route": "topical", "notes": "Cosmetic concentrations. Often combined with pre-synaptic (Argireline, SNAP-8) and nAChR-antagonist (Vialox) peptides." }, "evidenceLevel": "low", "sources": [ { "type": "manufacturer", "citation": "Lipotec / Lubrizol. \"Inyline® peptide solution (Acetyl Hexapeptide-30) technical data sheet.\" Lipotec S.A.U., Gavà, Barcelona." }, { "type": "review", "citation": "Errante F, Ledwoń P, Latajka R, Rovero P, Papini AM. \"Cosmeceutical peptides in the framework of sustainable wellness economy.\" Front Chem, 2020;8:572923. PMID: 33195061.", "pmid": "33195061" }, { "type": "pubmed", "citation": "Kim N, Stiegler AL, Cameron TO, et al. \"Lrp4 is a receptor for Agrin and forms a complex with MuSK.\" Cell, 2008;135(2):334-342 (agrin/LRP4/MuSK mechanism). PMID: 18848351.", "pmid": "18848351" } ], "interactionCoverage": "none-found", "related": [ "argireline", "snap-8", "pentapeptide-3", "syn-ake", "leuphasyl" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." } ], "moleculeClass": "peptide" }, { "id": "acetyl-hexapeptide-37", "name": "Acetyl Hexapeptide-37", "aliases": [ "Diffuporine", "Ac-Ser-Pro-Ala-Gly-Gly-Pro-NH2", "Ac-SPAGGP-NH2" ], "tier": "stub", "category": "cosmetic", "subcategory": "topical cosmetic peptide (aquaporin-3 inducer)", "class": "A synthetic N-acetylated hexapeptide (Ac-Ser-Pro-Ala-Gly-Gly-Pro-NH2) identified by combinatorial peptide screening as an inducer of aquaporin-3 (AQP3) expression in epidermal keratinocytes, used as a cosmetic hydration and barrier-support ingredient.", "tagline": "The Lipotec \"Diffuporine\" cosmetic peptide — identified by luciferase-reporter combinatorial screening as an AQP3 inducer; increases epidermal water transport and barrier proteins at cosmetic concentrations; entirely topical, no systemic development.", "oneLiner": "A synthetic acetylated hexapeptide (Ac-Ser-Pro-Ala-Gly-Gly-Pro-NH2, CAS 1447824-16-9) discovered by Lipotec (now Lubrizol) via a luciferase combinatorial peptide screen designed to identify inducers of the aquaporin-3 gene in keratinocytes. Aquaporin-3 is the dominant skin aquaporin, mediating water and glycerol flux from the basal epidermis to the stratum corneum. In-vitro data from the manufacturer show roughly two-fold upregulation of AQP3 transcription together with increases in collagen I and keratinocyte proliferation; the ingredient is marketed under the trade name Diffuporine® as a moisturising, barrier-supporting cosmetic active. No independent clinical trials; no systemic or drug development.", "sequence": "Ac-Ser-Pro-Ala-Gly-Gly-Pro-NH2", "molecularFormula": "C24H38N8O9", "molecularWeight": 582.61, "halfLife": { "value": null, "unit": null, "range": "topical only", "notes": "Systemic absorption from topical cosmetic formulations is minimal." }, "fdaStatus": "research-only", "approvalDetails": "Cosmetic ingredient; not a drug. INCI-listed.", "mechanism": "Induces transcriptional upregulation of the aquaporin-3 gene in epidermal keratinocytes (identified via a luciferase-reporter combinatorial screen). AQP3 is a hydroglyceroporin channel that transports water, glycerol, and urea from the basal epidermis toward the stratum corneum, contributing to both hydration and glycerol-dependent barrier lipid synthesis. Secondary manufacturer-reported effects include stimulation of keratinocyte proliferation and increased collagen I expression in dermal fibroblasts. Mechanism is cell-signalling / topical; no systemic activity is claimed.", "primaryUses": [ "Topical cosmetic moisturising / barrier-support formulations" ], "typicalDose": { "range": "3–5", "unit": "% (finished formulation, as supplied solution)", "frequency": "twice daily", "route": "topical", "notes": "Cosmetic concentrations. Supplied by the manufacturer as a pre-solubilised aqueous solution at approximately 100 ppm active peptide." }, "evidenceLevel": "low", "sources": [ { "type": "manufacturer", "citation": "Lipotec / Lubrizol. \"Diffuporine™ (Acetyl Hexapeptide-37) technical data sheet.\" CAS 1447824-16-9." }, { "type": "review", "citation": "Oshimura E, Sakamoto K. \"Amino acids, peptides, and proteins.\" In: Cosmetic Science and Technology: Theoretical Principles and Applications, 2017; pp. 285-303." }, { "type": "review", "citation": "Hara-Chikuma M, Verkman AS. \"Roles of aquaporin-3 in the epidermis.\" J Invest Dermatol, 2008;128(9):2145-2151 (AQP3 function in skin). PMID: 18548108.", "pmid": "18548108" } ], "interactionCoverage": "none-found", "related": [ "argireline", "matrixyl", "pal-ghk" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." } ], "moleculeClass": "peptide" }, { "id": "acetyl-octapeptide-3", "name": "Acetyl Octapeptide-3", "aliases": [ "SNAP-8", "Super Argireline" ], "tier": "stub", "category": "cosmetic", "subcategory": "Neuromuscular cosmeceutical peptide", "class": "Acetyl Octapeptide-3 is an extended version of Argireline (Acetyl Hexapeptide-3) — marketed as 'Super Argireline' for enhanced SNARE complex inhibition to reduce expression wrinkles.", "tagline": "The 'Super Argireline' — an extended SNAP-25 fragment peptide that reduces expression wrinkles without injections.", "oneLiner": "An 8-amino-acid acetylated peptide that inhibits SNARE complex assembly at the neuromuscular junction, reducing muscle contraction and expression wrinkles — marketed as a more potent topical alternative to Argireline.", "sequence": "Ac-EEMQRRAD", "molecularFormula": "C41H65N11O18", "molecularWeight": 1004.03, "halfLife": { "value": null, "unit": null, "range": "Hours (topical)", "notes": "Skin penetration is the limiting factor for efficacy." }, "fdaStatus": "supplement", "approvalDetails": "Cosmetic ingredient (Lipotec SNAP-8). Not FDA-approved as a drug. Positioned as second-generation Argireline with two extra amino acids for enhanced SNARE inhibition.", "mechanism": "Mimics the SNAP-25 protein's N-terminal domain, competitively inhibiting SNARE complex formation required for acetylcholine vesicle release at the neuromuscular junction. Reduces muscle contraction magnitude — a topical 'botox-like' mechanism.", "primaryUses": [ "Expression wrinkle reduction", "Topical alternative to botulinum toxin", "Anti-aging serums and creams" ], "typicalDose": { "range": "3-10", "unit": "% in formulation", "frequency": "twice daily", "route": "topical", "notes": "Often combined with Argireline and Leuphasyl. Effects gradual (2-4 weeks) and reversible." }, "evidenceLevel": "low", "sources": [ { "type": "review", "citation": "Blanes-Mira C, et al. \"A synthetic hexapeptide (Argireline) with antiwrinkle activity.\" Int J Cosmet Sci. 2002;24(5):303-310. PMID: 18498523.", "pmid": "18498523" } ], "interactionCoverage": "none-found", "related": [ "argireline", "snap-8", "leuphasyl", "pentapeptide-3", "syn-ake", "botulinum-toxin" ], "lastReviewed": "2026-04-21", "publishedAt": "2026-04-21", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." } ], "moleculeClass": "peptide" }, { "id": "acetyl-tetrapeptide-2", "name": "Acetyl Tetrapeptide-2", "aliases": [ "Uplevity", "Uplevity e-Lift" ], "tier": "stub", "category": "cosmetic", "subcategory": "topical cosmetic peptide (elastin / fibulin-5 / LOXL organizer)", "class": "A synthetic N-acetylated tetrapeptide marketed as a topical firming and lifting cosmetic ingredient claimed to organise dermal elastin and collagen via fibulin-5 and lysyl oxidase-like (LOXL) pathways.", "tagline": "Uplevity — a Lipotec firming tetrapeptide proposed to support dermal mechanotransduction by organising elastin, fibulin-5, and LOXL-family enzymes. Follow-on \"skin architect\" peptide marketed as alternative to pre-synaptic/post-synaptic muscle peptides; manufacturer-only efficacy data.", "oneLiner": "A synthetic acetylated tetrapeptide marketed by Lipotec (now Lubrizol) as Uplevity® (later repositioned as Uplevity® e-Lift). Claimed by the manufacturer to support dermal-epidermal junction integrity and re-organise the elastic fibre network by upregulating fibulin-5 and lysyl-oxidase-like enzymes (LOXL-1/LOXL-2). Manufacturer clinical data describe a ≈23 % increase in elastin and collagen after twice-daily 2 % application for approximately two months, with visible improvements in jawline and neck firmness. Sequence and molecular-formula data are not publicly disclosed in INCI registries — Lipotec treats the specific tetrapeptide structure as proprietary. Cosmetic ingredient; not a drug.", "sequence": "Proprietary acetylated tetrapeptide — specific sequence not disclosed by manufacturer", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": null, "range": "topical only", "notes": "Systemic absorption from topical cosmetic formulations is minimal." }, "fdaStatus": "research-only", "approvalDetails": "Cosmetic ingredient; not a drug. INCI name: Acetyl Tetrapeptide-2.", "mechanism": "Proposed by the manufacturer to act as a \"skin architect\" peptide upregulating fibulin-5 and lysyl-oxidase-like enzymes (LOXL-1, LOXL-2), which are responsible for nucleating tropoelastin onto microfibrils and catalysing the lysine-derived cross-links that mature elastin fibres. The pathway is of interest because dermal elastin organisation — rather than bulk elastin quantity — declines with age and photoaging. Independent mechanistic replication outside Lipotec is very limited; most published efficacy evidence is manufacturer-sponsored in-vitro and clinical work.", "primaryUses": [ "Topical cosmetic anti-aging formulations (firming / lifting / jawline definition)" ], "typicalDose": { "range": "2", "unit": "% (finished formulation, as supplied solution)", "frequency": "twice daily", "route": "topical", "notes": "Cosmetic concentrations. Manufacturer clinical study used 2 % finished-product concentration." }, "evidenceLevel": "low", "sources": [ { "type": "manufacturer", "citation": "Lipotec / Lubrizol. \"Uplevity® (Acetyl Tetrapeptide-2) and Uplevity® e-Lift peptide technical data sheet.\"" }, { "type": "review", "citation": "Ferreira MS, Magalhães MC, Sousa-Lobo JM, Almeida IF. \"Trending anti-aging peptides.\" Cosmetics, 2020;7(4):91." } ], "interactionCoverage": "none-found", "related": [ "matrixyl", "palmitoyl-tripeptide-38", "pal-ghk" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." } ], "moleculeClass": "peptide" }, { "id": "acetyl-tetrapeptide-5", "name": "Acetyl Tetrapeptide-5", "aliases": [ "Eyeseryl", "Ac-βAla-His-Ser-His", "Ac-bAla-His-Ser-His" ], "tier": "stub", "category": "cosmetic", "subcategory": "topical cosmetic peptide (anti-puffiness / anti-glycation)", "class": "A synthetic N-acetylated tetrapeptide (Ac-βAla-His-Ser-His) containing a non-proteinogenic β-alanine residue, developed as a topical cosmetic ingredient for reduction of periocular puffiness through anti-oedema and anti-glycation actions.", "tagline": "Eyeseryl — the anti-puffiness eye peptide. A β-alanine-containing acetyl-tetrapeptide claimed to reduce capillary permeability and inhibit glycation-driven cross-linking; low absolute concentrations (0.01 % active) but convincing before/after in manufacturer studies.", "oneLiner": "A synthetic tetrapeptide containing a non-proteinogenic β-alanine (Ac-β-Ala-His-Ser-His), developed by Lipotec (now Lubrizol) as Eyeseryl® and awarded the New Technology Award at the 2005 Health & Beauty America Conference. Manufacturer-sponsored in-vivo study in 20 female volunteers using a cream formulated to deliver 0.01 % active peptide (from a 10 % Eyeseryl solution) twice daily to the periocular area reported ≥30 % reduction in puffiness in 70 % of subjects at day 15 and 95 % at day 60. Proposed dual mechanism: reduction of vascular permeability (limiting interstitial fluid accumulation) and inhibition of non-enzymatic glycation of dermal proteins. Cosmetic ingredient; not FDA-approved for any medical use.", "sequence": "Ac-β-Ala-His-Ser-His", "molecularFormula": "C21H30N8O7", "molecularWeight": 506.52, "halfLife": { "value": null, "unit": null, "range": "topical only", "notes": "Systemic absorption from topical cosmetic formulations is minimal." }, "fdaStatus": "research-only", "approvalDetails": "Cosmetic ingredient; not a drug. INCI name: Acetyl Tetrapeptide-5.", "mechanism": "Proposed dual action on the two principal drivers of visible under-eye puffiness: (1) reduction of microvascular capillary permeability, limiting fluid accumulation in the periocular interstitial compartment — possibly via angiotensin-converting-enzyme (ACE) inhibition, consistent with histidine-rich peptides in that pharmacologic class; (2) inhibition of non-enzymatic glycation of collagen and elastin, which limits cross-link accumulation and preserves skin elasticity around the eye. Manufacturer in-vitro and in-vivo data support both mechanisms at low concentrations (~0.01 %). Independent mechanistic replication is limited; most published efficacy evidence is manufacturer-sponsored.", "primaryUses": [ "Topical cosmetic formulations for periocular puffiness and under-eye bags", "Anti-glycation formulations" ], "typicalDose": { "range": "1–10", "unit": "% (finished formulation, as supplied Eyeseryl solution)", "frequency": "twice daily", "route": "topical", "notes": "Cosmetic concentrations. Supplied solution typically delivers ~0.01 % active peptide at 10 % formulation use level." }, "evidenceLevel": "low", "sources": [ { "type": "manufacturer", "citation": "Lipotec / Lubrizol. \"Eyeseryl® (Acetyl Tetrapeptide-5) technical data sheet and clinical study brief.\"" }, { "type": "review", "citation": "Errante F, Ledwoń P, Latajka R, Rovero P, Papini AM. \"Cosmeceutical peptides in the framework of sustainable wellness economy.\" Front Chem, 2020;8:572923. PMID: 33195061.", "pmid": "33195061" }, { "type": "review", "citation": "Ferreira MS, Magalhães MC, Sousa-Lobo JM, Almeida IF. \"Trending anti-aging peptides.\" Cosmetics, 2020;7(4):91." } ], "interactionCoverage": "unreviewed", "related": [ "argireline", "matrixyl", "pal-ghk" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." } ], "moleculeClass": "peptide" }, { "id": "adamax", "name": "Adamax", "aliases": [ "Ac-MEHFPGP-AG-NH2", "N-acetyl Semax with adamantyl P21 modification", "Adamax peptide" ], "tier": "stub", "category": "cognitive", "subcategory": "Semax derivative (nootropic heptapeptide analog)", "class": "Synthetic 9-amino-acid peptide combining the N-acetylated Semax backbone (ACTH 4-10 analog) with an adamantyl-glycine modification derived from P21, designed for enhanced blood-brain barrier penetration and resistance to enzymatic degradation.", "tagline": "An enhanced Semax derivative with an adamantane modification borrowed from P21, studied in limited Russian research for BDNF upregulation and cognitive enhancement.", "oneLiner": "A second-generation nootropic peptide built by fusing Semax's ACTH(4-10) backbone to the adamantyl motif of P21, intended to combine Semax's neurotrophic mechanism with markedly improved CNS bioavailability.", "sequence": "Ac-Met-Glu-His-Phe-Pro-Gly-Pro-AdGly-NH2 (Ac-MEHFPGP-AG-NH2, where AG is an adamantylglycine C-terminal amide)", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": null, "range": "undetermined in humans", "notes": "The adamantane modification is designed to increase lipophilicity and blood-brain barrier penetration compared to Semax, which may extend central activity; no published pharmacokinetic data in humans." }, "fdaStatus": "research-only", "approvalDetails": "Not approved by any regulatory agency. A research-grade compound derived from the Russian nootropic peptide program at the Institute of Molecular Genetics of the Russian Academy of Sciences. Available only through research-chemical channels; no clinical trial registrations as of 2026.", "mechanism": "Inherits Semax's primary mechanism — upregulation of brain-derived neurotrophic factor (BDNF) and its TrkB receptor in the hippocampus and cortex, with modulation of dopaminergic and serotonergic signaling. The adamantyl-glycine C-terminal modification (derived from the P21 peptide) dramatically increases lipophilicity and blood-brain barrier penetration, and is reported to enhance peptide stability against enzymatic degradation. The net effect is proposed to be a more potent and longer-lasting version of the Semax effect profile.", "primaryUses": [ "Experimental cognitive enhancement (biohacker protocols)", "Research into enhanced Semax analogs with improved pharmacokinetics", "Off-label post-stroke recovery (extrapolated from Semax's approved Russian indication)" ], "typicalDose": { "range": "250–1000", "unit": "mcg", "frequency": "1x daily", "route": "intranasal or subcutaneous", "notes": "Community dosing extrapolated from Semax protocols. No human clinical data to establish a dose. Typical research reports plateau of effect above 10 mg per dose with increased peripheral side effects." }, "evidenceLevel": "low", "sources": [ { "type": "review", "citation": "Dolotov OV, Karpenko EA, Inozemtseva LS, et al. \"Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus.\" Brain Res, 2006;1117(1):54-60. PMID: 16996037.", "pmid": "16996037" }, { "type": "review", "citation": "Myasoedov NF, et al. \"Structure-activity relationships of regulatory heptapeptides: Semax and its derivatives.\" Russian Journal of Bioorganic Chemistry, 2018." } ], "interactionCoverage": "partial", "related": [ "semax", "p21", "selank", "cerebrolysin" ], "lastReviewed": "2026-04-20", "publishedAt": "2026-04-20", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "adipotide", "name": "Adipotide", "aliases": [ "FTPP", "Fat-Targeted Proapoptotic Peptide", "Prohibitin-TP01" ], "tier": "stub", "category": "research", "subcategory": "fat-tissue-targeted proapoptotic peptidomimetic", "class": "A chimeric peptide linking a white-adipose-tissue homing sequence to a pro-apoptotic mitochondrial-disruption sequence.", "tagline": "A preclinical concept that killed white adipose tissue by inducing vasculature apoptosis in obese rhesus monkeys — dramatic weight loss, but also nephrotoxicity that stopped it from advancing to humans.", "oneLiner": "A chimeric 29-amino-acid peptide developed by the Arap/Pasqualini lab at MD Anderson, combining a prohibitin-targeting sequence (homes to white adipose vasculature) with the pro-apoptotic D(KLAKLAK)2 sequence (disrupts mitochondrial membranes), designed to kill the blood vessels feeding fat tissue and thereby cause fat regression.", "sequence": "CKGGRAKDC-GG-D(KLAKLAK)2", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": null, "range": "preclinical; not characterized in humans", "notes": "Rhesus dosing was daily SC for ~28 days in primary studies." }, "fdaStatus": "preclinical", "approvalDetails": "Not approved. Strong preclinical data in obese rhesus monkeys (Barnhart et al., Sci Transl Med, 2011) showed ~11% body weight reduction and preferential fat loss over 28 days, but also produced nephrotoxicity (renal proximal tubule damage) in the monkey studies — which has prevented advancement into human trials despite enormous scientific interest.", "mechanism": "The CKGGRAKDC sequence binds prohibitin on the surface of endothelial cells specifically within white adipose tissue vasculature, concentrating the peptide there. The D(KLAKLAK)2 \"killer\" sequence then inserts into mitochondrial membranes of those endothelial cells, triggering apoptosis. Loss of the blood supply causes the downstream adipocytes to regress. The same prohibitin-targeting motif is also present in renal proximal tubule cells, which is the mechanistic origin of the nephrotoxicity.", "primaryUses": [ "Obesity research (preclinical)", "Tumor-targeting peptide research (same technology platform)", "Community use should be considered extremely dangerous given the documented primate nephrotoxicity" ], "typicalDose": { "range": "preclinical", "unit": "", "frequency": "historical: daily SC (primate studies)", "route": "subcutaneous", "notes": "No human dosing exists. Community use carries meaningful risk of acute kidney injury." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Barnhart KF, et al. \"A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys.\" Sci Transl Med, 2011;3:108ra112. PMID: 22072637.", "pmid": "22072637" }, { "type": "pubmed", "citation": "Kolonin MG, et al. \"Reversal of obesity by targeted ablation of adipose tissue.\" Nat Med, 2004;10:625-632. PMID: 15133506.", "pmid": "15133506" } ], "interactionCoverage": "unreviewed", "related": [ "aod-9604", "hgh-fragment-176-191", "tesofensine" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "adrenomedullin", "name": "Adrenomedullin", "aliases": [ "ADM", "AM", "pro-Adrenomedullin" ], "tier": "mid", "category": "cardiovascular", "subcategory": "endogenous vasoactive peptide", "class": "A 52-amino-acid vasodilatory peptide originally isolated from pheochromocytoma tissue, widely expressed in cardiovascular, pulmonary, and renal tissues.", "tagline": "A 52-amino-acid vasodilator hormone discovered in 1993, infused in small trials for pulmonary hypertension, ulcerative colitis and Crohn's disease; the bowel-disease trials missed their primary end points. Not approved.", "oneLiner": "A 52-amino-acid vasodilator peptide hormone with one disulfide bond and slight homology to calcitonin gene-related peptide, discovered in 1993 in human pheochromocytoma. Infused in small trials for pulmonary hypertension, ulcerative colitis and Crohn's disease; not approved.", "sequence": "YRQSMNNFQGLRSFGCRFGTCTVQKLAHQIYQFTDKDKDNVAPRSKISPQGY-NH2", "molecularFormula": "C264H406N80O77S3", "molecularWeight": "6029", "halfLife": { "value": null, "unit": null, "range": "about 22 minutes (circulating, in people)", "source": { "type": "pmid", "pmid": "8989240", "cite": "Meeran K, et al. \"Circulating adrenomedullin does not regulate systemic blood pressure but increases plasma prolactin after intravenous infusion in humans: a pharmacokinetic study.\" J Clin Endocrinol Metab, 1997;82(1):95-100. PMID: 8989240." } }, "fdaStatus": "research-only", "approvalDetails": "Not approved as a medicine; Drugs@FDA holds no application (openFDA, read September 30, 2026).", "mechanism": "Binds CLR (calcitonin receptor-like receptor) complexed with RAMP2 (forming AM1 receptor) and RAMP3 (AM2 receptor). Activates Gs → cAMP and eNOS → NO pathways. Produces vasodilation, positive inotropy, bronchodilation, natriuresis, angiogenesis, and anti-apoptotic effects. Upregulated in sepsis, heart failure, and renal injury as a compensatory protective response.", "primaryUses": [ "Inflammatory bowel disease (investigational, Japanese phase 2a trials)", "Pulmonary hypertension (early human study)", "Blood marker of severe inflammation (research)" ], "typicalDose": { "range": "10–15", "unit": "ng/kg/min", "frequency": "8 hours a day for 7 to 14 days", "route": "intravenous infusion", "notes": "The doses in the Japanese bowel-disease trials." }, "evidenceLevel": "medium", "sources": [ { "type": "fda", "citation": "FDA. Drugs@FDA (openFDA): no application for adrenomedullin. Read September 30, 2026." }, { "type": "pubmed", "citation": "Kita T, et al. \"Adrenomedullin for steroid-resistant ulcerative colitis: a randomized, double-blind, placebo-controlled phase-2a clinical trial.\" J Gastroenterol, 2021;56(2):147-157. PMID: 33140199.", "pmid": "33140199" }, { "type": "pubmed", "citation": "Kita T, et al. \"Adrenomedullin for biologic-resistant Crohn's disease: A randomized, double-blind, placebo-controlled phase 2a clinical trial.\" J Gastroenterol Hepatol, 2022;37(11):2051-2059. PMID: 35840351.", "pmid": "35840351" }, { "type": "pubmed", "citation": "Nagaya N, et al. \"Haemodynamic and hormonal effects of adrenomedullin in patients with pulmonary hypertension.\" Heart, 2000;84(6):653-8. PMID: 11083748.", "pmid": "11083748" }, { "type": "pubmed", "citation": "Kitamura K, et al. \"Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma.\" Biochem Biophys Res Commun, 1993;192(2):553-60. PMID: 8387282.", "pmid": "8387282" }, { "type": "pubmed", "citation": "Kita T, et al. \"Translational studies of adrenomedullin and related peptides regarding cardiovascular diseases.\" Hypertens Res, 2022;45(3):389-400. PMID: 34992239.", "pmid": "34992239" }, { "type": "pubmed", "citation": "Geven C, et al. \"Adrenomedullin and Adrenomedullin-Targeted Therapy As Treatment Strategies Relevant for Sepsis.\" Front Immunol, 2018;9:292. PMID: 29520277.", "pmid": "29520277" }, { "type": "pubmed", "citation": "Meeran K, et al. \"Circulating adrenomedullin does not regulate systemic blood pressure but increases plasma prolactin after intravenous infusion in humans: a pharmacokinetic study.\" J Clin Endocrinol Metab, 1997;82(1):95-100. PMID: 8989240.", "pmid": "8989240" } ], "interactionCoverage": "unreviewed", "related": [ "bnp", "anp", "endothelin-1" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-20", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "afamelanotide", "name": "Afamelanotide", "aliases": [ "Scenesse", "Melanotan I", "MT-I", "NDP-α-MSH", "Nle4-D-Phe7-α-MSH", "CUV1647" ], "tier": "stub", "category": "sexual-health", "subcategory": "selective MC1R agonist", "class": "A synthetic linear 13-amino-acid α-MSH analog with selective MC1R agonism, engineered with Nle4 and D-Phe7 substitutions for protease resistance.", "tagline": "An FDA-approved selective MC1R agonist marketed as Scenesse — the first-in-class treatment for erythropoietic protoporphyria (EPP), delivered as a subdermal implant.", "oneLiner": "A synthetic 13-amino-acid α-MSH analog (Nle4, D-Phe7) developed by Clinuvel Pharmaceuticals and FDA-approved in 2019 as Scenesse, delivered as a 16 mg slow-release subdermal implant for the rare disease erythropoietic protoporphyria.", "sequence": "Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2", "molecularFormula": "C78H111N21O19", "molecularWeight": 1646.85, "halfLife": { "value": 30, "unit": "minutes", "range": "plasma ~30 min; biological effect weeks", "notes": "Short plasma half-life but extended biological effect via MC1R-driven melanin synthesis; implant releases drug over ~2 days with photoprotection lasting ~2 months." }, "fdaStatus": "approved", "approvalDetails": "FDA-approved October 2019 as Scenesse (Clinuvel Pharmaceuticals) for adult patients with a history of phototoxic reactions from erythropoietic protoporphyria (EPP). Approved earlier in the EU and Australia.", "mechanism": "Selective agonist at MC1R on melanocytes, upregulating tyrosinase activity and driving eumelanin synthesis. The increased eumelanin pigmentation absorbs and dissipates UV and visible-light photons, providing photoprotection in EPP patients whose porphyrin accumulation causes severe light-induced pain. Unlike melanotan II, afamelanotide is linear and MC1R-selective, avoiding MC3R/MC4R-mediated nausea and sexual side effects.", "primaryUses": [ "Erythropoietic protoporphyria (EPP) photoprotection", "Vitiligo (investigational combination with narrowband UVB)" ], "typicalDose": { "range": "16", "unit": "mg", "frequency": "every 2 months", "route": "subdermal implant", "notes": "Scenesse implant is 16 mg, placed by a trained healthcare provider. Not available as an injectable." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Scenesse (afamelanotide) Prescribing Information. Clinuvel Pharmaceuticals." }, { "type": "clinical-trial", "citation": "Langendonk JG, et al. \"Afamelanotide for Erythropoietic Protoporphyria.\" N Engl J Med, 2015;373:48-59. PMID: 26132941.", "pmid": "26132941" } ], "interactionCoverage": "none-found", "related": [ "melanotan-ii", "pt-141" ], "lastReviewed": "2026-04-18", "publishedAt": "2026-04-18", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "ahk-cu", "name": "AHK-Cu", "aliases": [ "AHK copper peptide", "Ala-His-Lys-copper" ], "tier": "stub", "category": "cosmetic", "subcategory": "copper peptide", "class": "Tripeptide-copper complex (Ala-His-Lys chelated to Cu²⁺), the hair-follicle-targeted analog of GHK-Cu.", "tagline": "A tripeptide copper complex studied primarily for hair follicle stimulation and anagen induction in cosmetic applications.", "oneLiner": "A tripeptide (Ala-His-Lys) chelated with copper(II), structurally related to GHK-Cu but with research interest concentrated on hair follicle biology rather than skin remodeling.", "sequence": "Ala-His-Lys + Cu²⁺", "molecularFormula": "C15H26CuN6O4", "molecularWeight": 417.9, "halfLife": { "value": null, "unit": null, "range": "undetermined", "notes": "Topical application is primary route; systemic pharmacokinetics not established." }, "fdaStatus": "research-only", "approvalDetails": "Not approved as a drug. Used as a cosmetic ingredient in hair serums and scalp formulations. Most evidence is in vitro and animal-model.", "mechanism": "Copper-peptide complex that increases VEGF expression in dermal papilla cells and prolongs the anagen (growth) phase of the hair cycle in preclinical models. Copper itself is a cofactor for lysyl oxidase and several antioxidant enzymes; the tripeptide carrier is proposed to improve cellular delivery.", "primaryUses": [ "Hair growth and anti-alopecia (cosmetic research)", "Scalp formulations", "Wound healing (limited)" ], "typicalDose": { "range": "topical 0.1–0.5%", "unit": "", "frequency": "once or twice daily", "route": "topical", "notes": "Typical cosmetic formulation range. No systemic dosing established." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Pyo HK, et al. \"The effect of tripeptide-copper complex on human hair growth in vitro.\" Arch Pharm Res, 2007;30:834-839. PMID: 17703734.", "pmid": "17703734" }, { "type": "review", "citation": "Pickart L, Margolina A. \"Regenerative and Protective Actions of the GHK-Cu Peptide in the Light of the New Gene Data.\" Int J Mol Sci, 2018;19:1987. PMID: 29986520.", "pmid": "29986520" } ], "interactionCoverage": "unreviewed", "related": [ "ghk-cu" ], "lastReviewed": "2026-04-18", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "albiglutide", "name": "Albiglutide", "aliases": [ "Tanzeum", "Eperzan", "GSK716155" ], "tier": "full", "category": "metabolic", "subcategory": "long-acting GLP-1 agonist (withdrawn)", "class": "A long-acting GLP-1 receptor agonist created by fusing two tandem DPP-4-resistant GLP-1 mimetic sequences to recombinant human albumin.", "tagline": "A once-weekly GLP-1 receptor agonist made by fusing two copies of GLP-1 to human albumin. FDA-approved in 2014 as Tanzeum and now discontinued, it cut major cardiovascular events by 22% against placebo in Harmony Outcomes.", "oneLiner": "A recombinant albumin-fusion GLP-1 agonist (two tandem modified GLP-1 sequences linked to human serum albumin) approved by the FDA (2014) and EMA (2014) as once-weekly subcutaneous therapy for type 2 diabetes, voluntarily withdrawn by GSK in 2018 for commercial reasons; HARMONY-Outcomes demonstrated cardiovascular benefit comparable to other GLP-1 RAs before withdrawal.", "sequence": "Modified GLP-1(7-36) dimer fused to recombinant human albumin (~73 kDa total)", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": 5, "unit": "days", "range": "~5 days", "notes": "Long half-life driven by albumin fusion — supports once-weekly dosing." }, "fdaStatus": "discontinued", "approvalDetails": "FDA-approved April 15, 2014 as Tanzeum (GlaxoSmithKline, BLA 125431); Drugs@FDA lists its marketing status as discontinued. First approved in the EU in 2014 as Eperzan.", "mechanism": "GLP-1 receptor agonism with pharmacokinetics dominated by the albumin-fusion scaffold, which slows clearance and enables once-weekly administration. The GLP-1 moieties produce the canonical glucose-dependent insulin secretion, glucagon suppression, delayed gastric emptying, and central appetite suppression.", "primaryUses": [ "Type 2 diabetes mellitus (historical — FDA-approved 2014–2018)" ], "typicalDose": { "range": "30–50", "unit": "mg", "frequency": "once weekly", "route": "subcutaneous", "notes": "Labeled dose was 30 mg SC once weekly, uptitrated to 50 mg if needed." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "FDA. Tanzeum (albiglutide) prescribing information. GlaxoSmithKline, 2014." }, { "type": "pubmed", "citation": "Hernandez AF, et al. \"Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial.\" Lancet, 2018;392(10157):1519-1529. PMID: 30291013.", "pmid": "30291013" }, { "type": "pubmed", "citation": "Home PD, et al. \"Three-year data from 5 HARMONY phase 3 clinical trials of albiglutide in type 2 diabetes mellitus: Long-term efficacy with or without rescue therapy.\" Diabetes Res Clin Pract, 2017;131:49-60. PMID: 28683300.", "pmid": "28683300" }, { "type": "pubmed", "citation": "Reusch J, et al. \"Efficacy and safety of once-weekly glucagon-like peptide 1 receptor agonist albiglutide (HARMONY 1 trial): 52-week primary endpoint results from a randomized, double-blind, placebo-controlled trial in patients with type 2 diabetes mellitus not controlled on pioglitazone, with or without metformin.\" Diabetes Obes Metab, 2014;16(12):1257-64. PMID: 25155146.", "pmid": "25155146" }, { "type": "pubmed", "citation": "Weissman PN, et al. \"HARMONY 4: randomised clinical trial comparing once-weekly albiglutide and insulin glargine in patients with type 2 diabetes inadequately controlled with metformin with or without sulfonylurea.\" Diabetologia, 2014;57(12):2475-84. PMID: 25208756.", "pmid": "25208756" }, { "type": "pubmed", "citation": "Ahrén B, et al. \"HARMONY 3: 104-week randomized, double-blind, placebo- and active-controlled trial assessing the efficacy and safety of albiglutide compared with placebo, sitagliptin, and glimepiride in patients with type 2 diabetes taking metformin.\" Diabetes Care, 2014;37(8):2141-8. PMID: 24898304.", "pmid": "24898304" }, { "type": "pubmed", "citation": "Rosenstock J, et al. \"Impact of a Weekly Glucagon-Like Peptide 1 Receptor Agonist, Albiglutide, on Glycemic Control and on Reducing Prandial Insulin Use in Type 2 Diabetes Inadequately Controlled on Multiple Insulin Therapy: A Randomized Trial.\" Diabetes Care, 2020;43(10):2509-2518. PMID: 32694215.", "pmid": "32694215" }, { "type": "pubmed", "citation": "Rosenstock J, et al. \"Potential of albiglutide, a long-acting GLP-1 receptor agonist, in type 2 diabetes: a randomized controlled trial exploring weekly, biweekly, and monthly dosing.\" Diabetes Care, 2009;32(10):1880-6. PMID: 19592625.", "pmid": "19592625" }, { "type": "pubmed", "citation": "Ahrén B, et al. \"Albiglutide for the treatment of type 2 diabetes mellitus: An integrated safety analysis of the HARMONY phase 3 trials.\" Diabetes Res Clin Pract, 2017;126:230-239. PMID: 28284167.", "pmid": "28284167" }, { "type": "pubmed", "citation": "Fisher M, et al. \"Cardiovascular safety of albiglutide in the Harmony programme: a meta-analysis.\" Lancet Diabetes Endocrinol, 2015;3(9):697-703. PMID: 26276240.", "pmid": "26276240" }, { "type": "pubmed", "citation": "Gilbert MP, et al. \"Effect of albiglutide on cardiovascular outcomes in older adults: A post hoc analysis of a randomized controlled trial.\" Diabetes Obes Metab, 2024;26(5):1714-1722. PMID: 38317618.", "pmid": "38317618" }, { "type": "pubmed", "citation": "Ferreira JP, et al. \"Albiglutide in patients with type 2 diabetes and heart failure: a post-hoc analysis from Harmony Outcomes.\" Eur J Heart Fail, 2022;24(10):1792-1801. PMID: 36053803.", "pmid": "36053803" }, { "type": "pubmed", "citation": "Davidson JA, et al. \"Albiglutide efficacy and safety in the Latino/Hispanic subpopulation for the integrated phase III program.\" Postgrad Med, 2017;129(8):849-857. PMID: 29083275.", "pmid": "29083275" }, { "type": "pubmed", "citation": "Bush M, et al. \"Effects of multiple doses of albiglutide on the pharmacokinetics, pharmacodynamics, and safety of digoxin, warfarin, or a low-dose oral contraceptive.\" Postgrad Med, 2012;124(6):55-72. PMID: 23322139.", "pmid": "23322139" }, { "type": "pubmed", "citation": "Rhea EM, et al. \"Brain uptake pharmacokinetics of albiglutide, dulaglutide, tirzepatide, and DA5-CH in the search for new treatments of Alzheimer's and Parkinson's diseases.\" Tissue Barriers, 2024;12(4):2292461. PMID: 38095516.", "pmid": "38095516" }, { "type": "pubmed", "citation": "Young MA, et al. \"Clinical pharmacology of albiglutide, a GLP-1 receptor agonist.\" Postgrad Med, 2014;126(7):84-97. PMID: 25387217.", "pmid": "25387217" }, { "type": "pubmed", "citation": "Woodward HN, et al. \"Once-weekly albiglutide in the management of type 2 diabetes: patient considerations.\" Patient Prefer Adherence, 2014;8:789-803. PMID: 24926194.", "pmid": "24926194" }, { "type": "pubmed", "citation": "Rendell MS. \"Albiglutide for the management of type 2 diabetes.\" Expert Rev Endocrinol Metab, 2018;13(1):1-8. PMID: 30063441.", "pmid": "30063441" }, { "type": "fda", "citation": "FDA. Drugs@FDA (openFDA), BLA 125431: TANZEUM (albiglutide), GlaxoSmithKline LLC; original approval April 15, 2014; marketing status Discontinued. Read September 30, 2026." } ], "interactionCoverage": "studied", "related": [ "dulaglutide", "semaglutide", "liraglutide", "exenatide" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "A discontinued drug: S0's own examples include discontinued drugs." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "A discontinued drug: S0's own examples include discontinued drugs." } ], "moleculeClass": "protein", "moleculeClassBasis": "fusing" }, { "id": "alpha-msh", "name": "Alpha-MSH", "aliases": [ "α-MSH", "Alpha-Melanocyte Stimulating Hormone", "α-Melanotropin" ], "tier": "mid", "category": "immune", "subcategory": "endogenous melanocortin peptide", "class": "A 13-amino-acid endogenous peptide derived from POMC, with potent anti-inflammatory, immunomodulatory, and melanogenic effects via MC1R activation.", "tagline": "The endogenous anti-inflammatory melanocortin — the 13-amino-acid POMC fragment that PT-141, melanotan, setmelanotide, and the entire melanocortin drug class are built on.", "oneLiner": "A tridecapeptide cleaved from pro-opiomelanocortin (POMC) in the pituitary and skin, activating melanocortin-1 receptor (MC1R) to drive melanogenesis and producing potent anti-inflammatory effects via NF-κB suppression in immune cells.", "sequence": "Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2", "molecularFormula": "C77H109N21O19S", "molecularWeight": 1665.9, "halfLife": { "value": null, "unit": null, "range": "not reported in the sources read", "source": { "type": "none", "note": "searched PubMed on October 1, 2026; no human half-life figure in the sources read" } }, "fdaStatus": "research-only", "approvalDetails": "Not approved as a drug; no application for alpha-MSH appears in Drugs@FDA (read October 1, 2026). Three analogues are approved in the United States: afamelanotide (Scenesse, NDA 210797, October 8, 2019), setmelanotide (Imcivree, NDA 213793, November 25, 2020) and bremelanotide (Vyleesi, NDA 210557, June 21, 2019).", "mechanism": "Agonist at MC1R (melanocortin-1 receptor) on melanocytes (stimulates melanin production), immune cells (suppresses NF-κB, reduces TNF-α/IL-1β/IL-6, promotes IL-10), and keratinocytes. The His-Phe-Arg-Trp tetrapeptide core is the pharmacophore shared by all melanocortin drugs. Also acts at MC3R and MC5R with lower affinity. Central MC4R activation (by analogs) mediates appetite suppression and sexual arousal.", "primaryUses": [ "Melanocortin signaling research", "Anti-inflammatory pathway studies", "Parent molecule for melanocortin drug design", "UV protection and pigmentation research" ], "typicalDose": { "range": null, "unit": null, "frequency": null, "route": null, "notes": "Not a medicine. Its analogues are dosed as approved products; the tanning analogue in the 65-person study was given at 0.16 mg/kg subcutaneously in ten-day cycles." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Barnetson RS, et al. \"[Nle4-D-Phe7]-alpha-melanocyte-stimulating hormone significantly increased pigmentation and decreased UV damage in fair-skinned Caucasian volunteers.\" J Invest Dermatol, 2006;126(8):1869-78. PMID: 16763547.", "pmid": "16763547" }, { "type": "pubmed", "citation": "Fehm HL, et al. \"The melanocortin melanocyte-stimulating hormone/adrenocorticotropin(4-10) decreases body fat in humans.\" J Clin Endocrinol Metab, 2001;86(3):1144-8. PMID: 11238499.", "pmid": "11238499" }, { "type": "pubmed", "citation": "Diamond LE, et al. \"An effect on the subjective sexual response in premenopausal women with sexual arousal disorder by bremelanotide (PT-141), a melanocortin receptor agonist.\" J Sex Med, 2006;3(4):628-638. PMID: 16839319.", "pmid": "16839319" }, { "type": "pubmed", "citation": "Zierath D, et al. \"Plasma α-melanocyte stimulating hormone predicts outcome in ischemic stroke.\" Stroke, 2011;42(12):3415-20. PMID: 21960572.", "pmid": "21960572" }, { "type": "pubmed", "citation": "Catania A, et al. \"The melanocortin system in control of inflammation.\" ScientificWorldJournal, 2010;10:1840-53. PMID: 20852827.", "pmid": "20852827" }, { "type": "pubmed", "citation": "Brzoska T, et al. \"Alpha-melanocyte-stimulating hormone and related tripeptides: biochemistry, antiinflammatory and protective effects in vitro and in vivo, and future perspectives for the treatment of immune-mediated inflammatory diseases.\" Endocr Rev, 2008;29(5):581-602. PMID: 18612139.", "pmid": "18612139" } ], "interactionCoverage": "unreviewed", "related": [ "pt-141", "melanotan-ii", "afamelanotide", "setmelanotide", "kpv" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-20", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "alprostadil", "name": "Alprostadil", "aliases": [ "Prostaglandin E1", "PGE1", "Caverject", "Edex", "MUSE", "Prostin VR" ], "tier": "mid", "category": "sexual-health", "subcategory": "synthetic prostaglandin E1 (vasodilator)", "class": "Note: Alprostadil is a synthetic prostaglandin E1 (a lipid-based signaling molecule), not a peptide. It is included here because it is a widely-discussed injectable therapeutic commonly stocked alongside peptide therapeutics in compounding pharmacies and wellness clinics.", "tagline": "A synthetic prostaglandin E1 vasodilator FDA-approved for intracavernosal use in erectile dysfunction and for maintaining ductus arteriosus patency in neonatal congenital heart disease.", "oneLiner": "A vasodilator and smooth-muscle relaxant that binds prostaglandin EP2/EP4 receptors to raise intracellular cAMP; used for decades as a first-line intracavernosal injectable for erectile dysfunction and as a life-saving bridge therapy in ductus-dependent neonatal cardiac conditions.", "sequence": "Not applicable — Alprostadil is a 20-carbon eicosanoid (lipid), not a peptide.", "molecularFormula": "C20H34O5", "molecularWeight": 354.48, "halfLife": { "value": null, "unit": null, "range": "no figure on the label, which reports that about 80% is metabolised in one pass through the lungs", "source": { "type": "none", "note": "the Caverject label's Pharmacokinetics section states no half-life; PubMed searched October 1, 2026 and no human figure found in the sources read" } }, "fdaStatus": "approved", "approvalDetails": "Caverject (intracavernosal alprostadil), NDA 020379, approved July 6, 1995; Caverject Impulse, NDA 021212, June 11, 2002; Prostin VR Pediatric, NDA 018484, October 16, 1981, to keep the ductus arteriosus open in newborns (Drugs@FDA, read October 1, 2026). An intraurethral form is also marketed.", "mechanism": "Binds prostaglandin EP2 and EP4 receptors on smooth-muscle cells, activating adenylate cyclase to increase intracellular cAMP. Elevated cAMP causes smooth-muscle relaxation and arterial dilation. In the corpus cavernosum, this engorges the penis with blood to produce an erection without requiring intact nerve supply. In neonatal cardiac use, the same vasodilation keeps the ductus arteriosus patent. Also exhibits antiplatelet and anti-atherosclerotic effects via cAMP elevation in vascular tissue.", "primaryUses": [ "Erectile dysfunction (intracavernosal injection or intraurethral pellet)", "Maintenance of ductus arteriosus in neonatal congenital heart disease", "Peripheral arterial occlusive disease (approved in Europe)", "Raynaud phenomenon (off-label, mixed evidence)" ], "typicalDose": { "range": "1.25-2.5", "unit": "mcg", "frequency": "per dose, titrated", "route": "intracavernosal injection", "notes": "Caverject label: start at 2.5 mcg, or 1.25 mcg when the cause is purely neurogenic. The first injections are given in the clinic and the dose is raised to the lowest that works. The intraurethral form is dosed in hundreds of micrograms." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Caverject (alprostadil) prescribing information, sections 1, 2, 5 and 12.3 (DailyMed SPL version 19, effective May 13, 2024; read October 1, 2026)." }, { "type": "pubmed", "citation": "Linet OI, et al. \"Efficacy and safety of intracavernosal alprostadil in men with erectile dysfunction. The Alprostadil Study Group.\" N Engl J Med, 1996;334(14):873-7. PMID: 8596569.", "pmid": "8596569" }, { "type": "pubmed", "citation": "Shabsigh R, et al. \"Intracavernous alprostadil alfadex is more efficacious, better tolerated, and preferred over intraurethral alprostadil plus optional actis: a comparative, randomized, crossover, multicenter study.\" Urology, 2000;55(1):109-13. PMID: 10654905.", "pmid": "10654905" }, { "type": "pubmed", "citation": "Werthman P, et al. \"MUSE therapy: preliminary clinical observations.\" Urology, 1997;50(5):809-11. PMID: 9372900.", "pmid": "9372900" }, { "type": "pubmed", "citation": "Tsai YS, et al. \"Safety and efficacy of alprostadil sterile powder (S. Po., CAVERJECT) in diabetic patients with erectile dysfunction.\" Eur Urol, 2000;38(2):177-83. PMID: 10895010.", "pmid": "10895010" }, { "type": "pubmed", "citation": "Porst H. \"The rationale for prostaglandin E1 in erectile failure: a survey of worldwide experience.\" J Urol, 1996;155(3):802-15. PMID: 8583582.", "pmid": "8583582" } ], "interactionCoverage": "partial", "related": [ "pt-141", "oxytocin", "kisspeptin-10" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-20", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "small-molecule", "moleculeClassBasis": "prostaglandin E1" }, { "id": "amycretin", "name": "Amycretin", "aliases": [ "NNC0487-0111" ], "tier": "mid", "category": "pipeline", "subcategory": "unimolecular GLP-1 + amylin dual agonist", "class": "A unimolecular dual agonist at the GLP-1 and amylin receptors, developed by Novo Nordisk in oral and subcutaneous formulations.", "tagline": "Novo Nordisk's investigational single-molecule GLP-1 and amylin receptor agonist, tested as a daily tablet and a weekly injection: in a phase 1b/2a trial the 60 mg weekly dose gave a mean weight change of -24.3% at 36 weeks against -1.1% on placebo. Not approved anywhere.", "oneLiner": "A novel unimolecular dual agonist at the GLP-1 and amylin receptors, developed by Novo Nordisk as a single-peptide combination of the two leading metabolic mechanisms (one of which, amylin, has been validated by pramlintide and is being independently pursued as cagrilintide and petrelintide); oral Phase 1b data in The Lancet in 2024 reported approximately 13% weight loss at 12 weeks, and subcutaneous Phase 1b data reported in 2025 reached approximately 22% at 36 weeks, positioning amycretin as Novo's leading late-stage response to the triple-agonist class.", "sequence": null, "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": null, "range": "suitable for weekly SC / daily oral", "notes": "SC formulation dosed weekly; oral formulation dosed daily.", "source": { "type": "qualitative", "note": "a description with no figure; no half-life measurement is cited for it" } }, "fdaStatus": "clinical-trials", "approvalDetails": "Investigational; not approved anywhere. Drugs@FDA holds no application and EMA's register has no entry (both read September 30, 2026). Published human data: a first-in-human oral phase 1 trial (144 participants) and a subcutaneous phase 1b/2a trial (125 participants), both 2025.", "mechanism": "A single peptide that activates both the GLP-1 receptor and the amylin receptor, combining the appetite-suppressant and gastric-emptying effects of GLP-1 agonism with the satiety, glucagon-suppression, and gastric-emptying effects of amylin agonism. The unimolecular approach mirrors the success of tirzepatide's GLP-1/GIP dual agonism in a single molecule rather than requiring a fixed-dose combination like CagriSema.", "primaryUses": [ "Chronic weight management (Phase 1b positive; Phase 3 initiating 2026)", "Research into unimolecular multi-receptor agonism" ], "typicalDose": { "range": "1.25–60", "unit": "mg", "frequency": "weekly (SC) or daily (oral) — trial doses", "route": "subcutaneous or oral", "notes": "Trial doses only: weekly SC escalations to maintenance doses of 1.25, 5, 20 or 60 mg (phase 1b/2a); daily oral escalations up to 50 mg or 2 × 50 mg (phase 1)." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "Dahl K, et al. \"Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study.\" Lancet, 2025;406(10499):149-162. PMID: 40550231.", "pmid": "40550231" }, { "type": "pubmed", "citation": "Gasiorek A, et al. \"Safety, tolerability, pharmacokinetics, and pharmacodynamics of the first-in-class GLP-1 and amylin receptor agonist, amycretin: a first-in-human, phase 1, double-blind, randomised, placebo-controlled trial.\" Lancet, 2025;406(10499):135-148. PMID: 40550229.", "pmid": "40550229" }, { "type": "pubmed", "citation": "Kuhre RE, et al. \"The effect of amycretin, a unimolecular glucagon-like peptide-1 and amylin receptor agonist, on body weight and metabolic dysfunction in mice and rats.\" EBioMedicine, 2025;118:105862. PMID: 40706446.", "pmid": "40706446" }, { "type": "pubmed", "citation": "Fu L, et al. \"Amycretin in obesity: Mechanisms, clinical efficacy, and future perspectives.\" Metabolism, 2026;179:156594. PMID: 41850421.", "pmid": "41850421" }, { "type": "fda", "citation": "FDA. Drugs@FDA (openFDA): no application for amycretin. Read September 30, 2026." }, { "type": "other", "citation": "European Medicines Agency. Medicines register (centrally authorised human medicines): no entry for amycretin. Read September 30, 2026." } ], "interactionCoverage": "none-found", "related": [ "cagrisema", "petrelintide", "orforglipron" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." } ], "moleculeClass": "peptide" }, { "id": "amylin", "name": "Amylin", "aliases": [ "Islet Amyloid Polypeptide", "IAPP" ], "tier": "mid", "category": "metabolic", "subcategory": "endogenous pancreatic hormone", "class": "A 37-amino-acid peptide hormone co-secreted with insulin from pancreatic beta cells, involved in glucoregulation, satiety, and gastric emptying.", "tagline": "Insulin's co-secreted partner — the native satiety hormone behind pramlintide (Symlin) and the amylin component of CagriSema.", "oneLiner": "A 37-amino-acid neuroendocrine peptide co-packaged and co-released with insulin from beta cell granules, producing complementary glucoregulatory effects including appetite suppression, gastric slowing, and glucagon inhibition.", "sequence": "KCNTATCATQRLANFLVHSSNNFGAILSSTNVGSNTY-NH2", "molecularFormula": "C165H261N51O55S2", "molecularWeight": 3904.3, "halfLife": { "value": null, "unit": null, "range": "not reported for human amylin in the sources read", "source": { "type": "none", "note": "searched PubMed on October 1, 2026; no human half-life for amylin itself in the sources read. Pramlintide, the approved analogue, is reported at 30 to 50 minutes" } }, "fdaStatus": "research-only", "approvalDetails": "Human amylin is not approved as a drug; no application appears in Drugs@FDA (read October 1, 2026). Pramlintide (Symlin) is the approved analogue; cagrilintide and amycretin are investigational.", "mechanism": "Binds calcitonin receptor (CTR) in complex with receptor activity-modifying proteins (RAMPs 1–3) to form AMY1–3 receptors. Slows gastric emptying, suppresses postprandial glucagon secretion, promotes satiety via area postrema signaling. Complements insulin action in postprandial glucose regulation.", "primaryUses": [ "Postprandial glucoregulation (via pramlintide)", "Satiety and appetite research", "Diabetes pathophysiology studies (amyloid aggregation)", "Obesity pharmacology (cagrilintide/CagriSema)" ], "typicalDose": { "range": null, "unit": null, "frequency": null, "route": null, "notes": "Human amylin is not given as a drug. Its analogues are: pramlintide with meals, cagrilintide and amycretin weekly in trials." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Dahl K, et al. \"Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study.\" Lancet, 2025;406(10499):149-162. PMID: 40550231.", "pmid": "40550231" }, { "type": "pubmed", "citation": "Ishibashi C, et al. \"Decreased islet amyloid polypeptide staining in the islets of insulinoma patients.\" Islets, 2024;16(1):2379650. PMID: 39028826.", "pmid": "39028826" }, { "type": "review", "citation": "Kruse T, et al. \"Development of Cagrilintide, a Long-Acting Amylin Analogue.\" J Med Chem, 2021;64(15):11183-11194. PMID: 34288673.", "pmid": "34288673" }, { "type": "pubmed", "citation": "Hay DL, et al. \"Amylin: Pharmacology, Physiology, and Clinical Potential.\" Pharmacol Rev, 2015;67(3):564-600. PMID: 26071095.", "pmid": "26071095" }, { "type": "pubmed", "citation": "Westermark P, et al. \"Islet amyloid polypeptide, islet amyloid, and diabetes mellitus.\" Physiol Rev, 2011;91(3):795-826. PMID: 21742788.", "pmid": "21742788" } ], "interactionCoverage": "unreviewed", "related": [ "pramlintide", "cagrilintide", "cagrisema", "semaglutide" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-20", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "anamorelin", "name": "Anamorelin", "aliases": [ "Adlumiz", "ONO-7643", "RC-1291", "anamorelin hydrochloride" ], "tier": "mid", "category": "growth-hormone", "subcategory": "orally active ghrelin receptor agonist", "class": "A small-molecule orally active ghrelin receptor (GHS-R1a) agonist, structurally distinct from peptidic ghrelin analogs, developed for cancer cachexia.", "tagline": "An oral ghrelin agonist that adds lean mass in cancer cachexia but never beat placebo on strength: approved in Japan, not in the US.", "oneLiner": "An orally active ghrelin receptor agonist developed for cancer cachexia, where it raises weight, appetite and lean mass.", "sequence": null, "molecularFormula": "C31H42N6O3", "molecularWeight": 546.7, "halfLife": { "value": null, "unit": null, "range": "6 to 7 hours (terminal)", "source": { "type": "pmid", "pmid": "26640742", "cite": "Leese PT, et al. \"An open-label clinical trial of the effects of age and gender on the pharmacodynamics, pharmacokinetics and safety of the ghrelin receptor agonist anamorelin.\" Clin Pharmacol Drug Dev, 2015;4(2):112-120. PMID: 26640742." } }, "fdaStatus": "not-approved-us", "approvalDetails": "Approved in Japan on January 22, 2021 as Adlumiz (Ono Pharmaceutical) for cancer cachexia. Not approved in the US, where no application appears in Drugs@FDA; Helsinn ran two further randomised phase 3 trials in lung cancer that completed in 2022 and 2023. The original phase 3 programme met its lean-mass endpoint and missed handgrip strength.", "mechanism": "Full agonist at the growth hormone secretagogue receptor type 1a (GHS-R1a, the ghrelin receptor) expressed in the hypothalamus and pituitary somatotrophs. Stimulates GH release and, independently, triggers downstream appetite and food intake signaling through NPY/AgRP hypothalamic circuits. Net clinical effect in cachexia is improved appetite, increased lean body mass, and modest weight gain, without meaningful improvements in physical function in the Phase 3 program.", "primaryUses": [ "Cancer cachexia (approved in Japan)", "Appetite and lean-mass loss in advanced cancer (phase 3)" ], "typicalDose": { "range": "100", "unit": "mg/day", "frequency": "once daily (oral)", "route": "oral", "notes": "Administered on an empty stomach, per the Japanese label." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Temel JS, et al. \"Anamorelin in patients with non-small-cell lung cancer and cachexia (ROMANA 1 and ROMANA 2): results from two randomised, double-blind, phase 3 trials.\" Lancet Oncol, 2016;17(4):519-531. PMID: 26906526.", "pmid": "26906526" }, { "type": "pubmed", "citation": "Katakami N, et al. \"Anamorelin (ONO-7643) for the treatment of patients with non-small cell lung cancer and cachexia: Results from a randomized, double-blind, placebo-controlled, multicenter study of Japanese patients (ONO-7643-04).\" Cancer, 2018;124(3):606-616. PMID: 29205286.", "pmid": "29205286" }, { "type": "pubmed", "citation": "Takayama K, et al. \"Anamorelin (ONO-7643) in Japanese patients with non-small cell lung cancer and cachexia: results of a randomized phase 2 trial.\" Support Care Cancer, 2016;24(8):3495-505. PMID: 27005463.", "pmid": "27005463" }, { "type": "pubmed", "citation": "Garcia JM, et al. \"Pharmacodynamic hormonal effects of anamorelin, a novel oral ghrelin mimetic and growth hormone secretagogue in healthy volunteers.\" Growth Horm IGF Res, 2009;19(3):267-73. PMID: 19196529.", "pmid": "19196529" }, { "type": "pubmed", "citation": "Naito T, et al. \"A multicenter, open-label, single-arm study of anamorelin (ONO-7643) in patients with cancer cachexia and low body mass index.\" Cancer, 2022;128(10):2025-2035. PMID: 35195274.", "pmid": "35195274" }, { "type": "pubmed", "citation": "Garcia JM, et al. \"Effect on body weight and safety of RC-1291, a novel, orally available ghrelin mimetic and growth hormone secretagogue: results of a phase I, randomized, placebo-controlled, multiple-dose study in healthy volunteers.\" Oncologist, 2007;12(5):594-600. PMID: 17522248.", "pmid": "17522248" }, { "type": "pubmed", "citation": "Leese PT, et al. \"An open-label clinical trial of the effects of age and gender on the pharmacodynamics, pharmacokinetics and safety of the ghrelin receptor agonist anamorelin.\" Clin Pharmacol Drug Dev, 2015;4(2):112-120. PMID: 26640742.", "pmid": "26640742" }, { "type": "other", "citation": "US FDA, Drugs@FDA (openFDA): no application for anamorelin. Read September 30, 2026." }, { "type": "other", "citation": "Ono Pharmaceutical, press release, January 22, 2021: Japanese approval of Adlumiz (anamorelin) for cancer cachexia. Read September 30, 2026." }, { "type": "clinicaltrials", "citation": "ClinicalTrials.gov NCT03743064 and NCT03743051: Helsinn's two phase 3 trials in lung cancer, 318 participants each, completed 2022 and 2023. Read September 30, 2026." } ], "interactionCoverage": "none-found", "related": [ "mk-677", "ghrp-2", "ghrp-6", "macimorelin", "relamorelin" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": "Japan (PMDA)", "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.2.4", "named": true, "wording": "anamorelin", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.2.4", "named": true, "wording": "anamorelin", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "small-molecule", "moleculeClassBasis": "small-molecule" }, { "id": "angiotensin-ii", "name": "Angiotensin II", "aliases": [ "Giapreza", "Ang II", "AT-II", "LJPC-501", "synthetic human angiotensin II" ], "tier": "mid", "category": "cardiovascular", "subcategory": "AT1 / AT2 receptor agonist (vasopressor)", "class": "Synthetic human angiotensin II — the endogenous octapeptide effector of the renin-angiotensin-aldosterone system — developed and marketed by La Jolla Pharmaceutical Company (later acquired by Innoviva) as Giapreza® for catecholamine-refractory distributive shock.", "tagline": "The body's blood-pressure hormone as an ICU drug: Giapreza raised pressure in seven of ten patients in shock; survival did not significantly change.", "oneLiner": "An eight-amino-acid vasoconstrictor hormone, given as Giapreza by intravenous infusion to raise blood pressure in septic or distributive shock.", "sequence": "Asp-Arg-Val-Tyr-Ile-His-Pro-Phe", "molecularFormula": "C50H71N13O12", "molecularWeight": 1046.18, "halfLife": { "value": 1, "unit": "minutes", "range": "less than 1 minute (plasma, intravenous)", "notes": "Extremely short plasma half-life; degraded by aminopeptidase A and angiotensinases in plasma and tissues. Continuous IV infusion required; dose adjustment not needed in renal or hepatic impairment because clearance is not by either organ.", "source": { "type": "label", "ref": "Giapreza prescribing information, section 12.3 (DailyMed version 18, effective July 22, 2026; read September 30, 2026)" } }, "fdaStatus": "approved", "approvalDetails": "FDA-approved as Giapreza (angiotensin II), NDA 209360, to increase blood pressure in adults with septic or other distributive shock; intravenous infusion from 20 ng/kg/min, no more than 80 in the first 3 hours and 40 for maintenance.", "mechanism": "Agonist at the AT1 receptor (Gq-coupled) on vascular smooth muscle, producing direct vasoconstriction independent of catecholamine receptors and vasopressin receptors. This third vasoconstrictor pathway is often preserved in septic shock when adrenergic and vasopressin responsiveness are impaired by receptor desensitisation, uncoupling, and depletion of the underlying ligands. Additional AT1-mediated effects include aldosterone release (Gq, adrenal glomerulosa), sympathetic facilitation (central and peripheral), and renal tubular sodium reabsorption. The AT2 receptor produces opposing vasodilatory effects but is quantitatively minor at therapeutic doses. Clinical dosing is titrated to MAP with maximum recommended doses of 80 ng/kg/min in the first 3 hours and 40 ng/kg/min for maintenance, as a catecholamine-sparing addition rather than replacement.", "primaryUses": [ "Septic or other distributive shock in adults (US label)" ], "typicalDose": { "range": "20 ng/kg/min starting; up to 80 ng/kg/min max for first 3 hours, then up to 40 ng/kg/min", "unit": "ng/kg/min (continuous IV infusion)", "frequency": "continuous infusion", "route": "intravenous (central line preferred)", "notes": "Use with VTE prophylaxis due to thromboembolism signal (13% vs 5% in ATHOS-3). ACE inhibitor co-administration may potentiate effect; ARB co-administration may attenuate it. Not cleared renally or hepatically — no dose adjustment in organ dysfunction." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Giapreza (angiotensin II) injection Prescribing Information, sections 1 and 2 (DailyMed version 18, effective July 22, 2026; read September 30, 2026)." }, { "type": "pubmed", "citation": "Khanna A, et al. \"Angiotensin II for the Treatment of Vasodilatory Shock.\" N Engl J Med, 2017;377(5):419-430. PMID: 28528561.", "pmid": "28528561" }, { "type": "pubmed", "citation": "Chawla LS, et al. \"Intravenous angiotensin II for the treatment of high-output shock (ATHOS trial): a pilot study.\" Crit Care, 2014;18(5):534. PMID: 25286986.", "pmid": "25286986" }, { "type": "pubmed", "citation": "Leisman DE, et al. \"ACE inhibitors and angiotensin receptor blockers differentially alter the response to angiotensin II treatment in vasodilatory shock.\" Crit Care, 2024;28(1):130. PMID: 38637829.", "pmid": "38637829" }, { "type": "fda-pi", "citation": "Giapreza® (angiotensin II) Prescribing Information. La Jolla Pharmaceutical Company / Innoviva Specialty Therapeutics. Initial US approval December 21, 2017." }, { "type": "other", "citation": "US FDA, Drugs@FDA (openFDA): GIAPREZA, NDA 209360, La Jolla Pharmaceutical, prescription. Read September 30, 2026." } ], "interactionCoverage": "label", "related": [ "vasopressin", "terlipressin" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "anp", "name": "ANP", "aliases": [ "Atrial Natriuretic Peptide", "Atrial Natriuretic Factor", "ANF", "Atriopeptin" ], "tier": "mid", "category": "cardiovascular", "subcategory": "endogenous natriuretic peptide", "class": "A 28-amino-acid peptide hormone secreted by atrial cardiomyocytes in response to atrial stretch, regulating blood pressure, blood volume, and sodium balance.", "tagline": "The heart's salt-excreting hormone: sold in Japan as carperitide since 1995, while US kidney trials of anaritide found no benefit.", "oneLiner": "A 28-amino-acid hormone released by stretched heart atria that increases salt and water excretion, widens vessels and suppresses renin and aldosterone.", "sequence": "SLRRSSCFGGRMDRIGAQSGLGCNSFRY (disulfide: Cys7–Cys23)", "molecularFormula": "C127H203N45O39S3", "molecularWeight": 3080.5, "halfLife": { "value": null, "unit": null, "range": "not reported in the sources read", "source": { "type": "none", "note": "searched on September 30, 2026; no half-life reported in the sources read" } }, "fdaStatus": "not-approved-us", "approvalDetails": "Not approved in the US; no application for ANP, anaritide or carperitide appears in Drugs@FDA. Carperitide (Hanp), recombinant human ANP, was launched in Japan in 1995 for acute heart failure. US trials of anaritide in acute kidney failure and contrast injury found no benefit.", "mechanism": "Binds NPR-A (natriuretic peptide receptor A), a transmembrane guanylyl cyclase, increasing intracellular cGMP in kidney, vasculature, and adrenal glands. Effects: afferent arteriolar dilation + efferent constriction (increases GFR), suppresses aldosterone secretion, relaxes vascular smooth muscle, inhibits cardiac fibrosis.", "primaryUses": [ "Acute heart failure (carperitide, Japan)" ], "typicalDose": { "range": null, "unit": null, "frequency": null, "route": null, "notes": "Endogenous hormone. Carperitide (Japan) dosed at 0.025–0.05 mcg/kg/min IV infusion." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Allgren RL, et al. \"Anaritide in acute tubular necrosis. Auriculin Anaritide Acute Renal Failure Study Group.\" N Engl J Med, 1997;336(12):828-34. PMID: 9062091.", "pmid": "9062091" }, { "type": "pubmed", "citation": "Lewis J, et al. \"Atrial natriuretic factor in oliguric acute renal failure. Anaritide Acute Renal Failure Study Group.\" Am J Kidney Dis, 2000;36(4):767-74. PMID: 11007679.", "pmid": "11007679" }, { "type": "pubmed", "citation": "Kurnik BR, et al. \"Prospective study of atrial natriuretic peptide for the prevention of radiocontrast-induced nephropathy.\" Am J Kidney Dis, 1998;31(4):674-80. PMID: 9531185.", "pmid": "9531185" }, { "type": "pubmed", "citation": "Sezai A, et al. \"Results of low-dose carperitide infusion in high-risk patients undergoing coronary artery bypass grafting.\" Ann Thorac Surg, 2013;96(1):119-26. PMID: 23702231.", "pmid": "23702231" }, { "type": "pubmed", "citation": "Weidmann P, et al. \"Atrial natriuretic peptide in man.\" J Steroid Biochem, 1989;32(1B):229-41. PMID: 2521524.", "pmid": "2521524" }, { "type": "pubmed", "citation": "de Bold AJ, et al. \"A rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats.\" Life Sci, 1981;28(1):89-94. PMID: 7219045.", "pmid": "7219045" }, { "type": "pubmed", "citation": "Potter LR, et al. \"Natriuretic peptides, their receptors, and cyclic guanosine monophosphate-dependent signaling functions.\" Endocr Rev, 2006;27(1):47-72. PMID: 16291870.", "pmid": "16291870" }, { "type": "other", "citation": "The Pharma Letter. Zeria Pharmaceuticals launches Hanp Injection (carperitide) in Japan for acute heart failure. May 28, 1995. Read September 30, 2026." }, { "type": "other", "citation": "US FDA, Drugs@FDA (openFDA): no application for ANP, anaritide or carperitide. Read September 30, 2026." } ], "interactionCoverage": "unreviewed", "related": [ "bnp", "nesiritide", "carperitide", "ularitide" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-20", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "The same molecule as carperitide, which is approved in Japan (Hanp)." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "The same molecule as carperitide, which is approved in Japan (Hanp)." } ], "moleculeClass": "peptide", "statusVerified": { "date": "2026-09-30", "source": "openFDA (no record); The Pharma Letter, May 28, 1995: carperitide (Hanp) launched in Japan for acute heart failure" } }, { "id": "aod-9604", "name": "AOD-9604", "aliases": [ "AOD9604", "hGH fragment 176-191" ], "tier": "full", "category": "metabolic", "subcategory": "GH fragment", "class": "A synthetic 16-amino-acid peptide: human growth hormone residues 177–191 with a tyrosine added at the front, the same sequence as residues 176–191.", "tagline": "A 16-amino-acid piece of growth hormone that trimmed fat in obese rodents; in company trials it was well tolerated, but its largest obesity trial found no significant weight loss and development stopped in 2007.", "oneLiner": "A synthetic fragment from the C-terminal end of human growth hormone that reduced weight gain and increased fat breakdown in obese rodents without whole growth hormone's effects on blood sugar; the oral obesity programme ended in 2007 when a 24-week trial of 536 adults found no significant weight loss.", "sequence": "YLRIVQCRSVEGSCGF (Tyr-hGH(177-191))", "molecularFormula": "C78H123N23O23S2", "molecularWeight": 1815.1, "halfLife": { "value": null, "unit": null, "range": "Not published for people", "notes": "No human half-life has been published. In serum and urine in the laboratory, one metabolite (CRSVEGSCG) was markedly more stable than the parent peptide (2015)." }, "fdaStatus": "research-only", "approvalDetails": "Not approved anywhere as a medicine. Its developer ran six placebo-controlled trials in Australia between 2001 and 2006 and ended obesity development in 2007 after a 24-week trial found no significant weight loss. A panel convened for the developer later judged it 'generally recognized as safe' for intended uses in foods, a self-determination rather than an FDA decision.", "mechanism": "Does not bind or activate the growth hormone receptor: it did not compete with growth hormone for receptor binding or make receptor-bearing cells proliferate. In obese rats and mice it reduced weight gain and increased fat oxidation and lipolysis without the high blood sugar or insulin resistance that whole growth hormone causes; it raised beta3-adrenergic receptor expression, but its effect did not depend on that receptor. In people it did not raise IGF-1 or impair glucose tolerance (company trials, 2013 report).", "primaryUses": [ "Former oral obesity drug candidate (development ended 2007)", "Research reagent", "Unapproved 'fat-loss' use, sold online" ], "typicalDose": { "range": "250–500", "unit": "mcg", "frequency": "daily", "route": "subcutaneous", "notes": "Community figures, not medical guidance. The human trials gave it by mouth at 0.25–54 mg a day, or as single intravenous doses of 25–400 µg/kg; none tested daily injections under the skin." }, "evidenceLevel": "medium", "sources": [ { "type": "clinical-trial", "citation": "Stier H, et al. \"Safety and tolerability of the hexadecapeptide AOD9604 in humans.\" J Endocrinol Metab, 2013;3(1-2):7-15. doi:10.4021/jem157w (not PubMed-indexed; read in full September 27, 2026)." }, { "type": "pubmed", "citation": "Ng FM, et al. \"Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone.\" Horm Res, 2000;53(6):274-8. PMID: 11146367.", "pmid": "11146367" }, { "type": "pubmed", "citation": "Heffernan M, et al. \"The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta(3)-AR knock-out mice.\" Endocrinology, 2001;142(12):5182-9. PMID: 11713213.", "pmid": "11713213" }, { "type": "pubmed", "citation": "Wilding J. \"AOD-9604 Metabolic.\" Curr Opin Investig Drugs, 2004;5(4):436-40. PMID: 15134286.", "pmid": "15134286" }, { "type": "pubmed", "citation": "Cox HD, et al. \"Detection and in vitro metabolism of AOD9604.\" Drug Test Anal, 2015;7(1):31-8. PMID: 25208511.", "pmid": "25208511" }, { "type": "pubmed", "citation": "Kwon DR, et al. \"Effect of Intra-articular Injection of AOD9604 with or without Hyaluronic Acid in Rabbit Osteoarthritis Model.\" Ann Clin Lab Sci, 2015;45(4):426-32. PMID: 26275694.", "pmid": "26275694" }, { "type": "pubmed", "citation": "Heffernan MA, et al. \"Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment.\" Int J Obes Relat Metab Disord, 2001;25(10):1442-9. PMID: 11673763.", "pmid": "11673763" }, { "type": "pubmed", "citation": "Orlovius AK, et al. \"AOD-9604 does not influence the WADA hGH isoform immunoassay.\" Drug Test Anal, 2013;5(11-12):850-2. PMID: 24124033.", "pmid": "24124033" }, { "type": "pubmed", "citation": "Vanhee C, et al. \"Identification and characterization of peptide drugs in unknown pharmaceutical preparations seized by the Belgian authorities: case report on AOD9604.\" Drug Test Anal, 2014;6(9):964-8. PMID: 24976118.", "pmid": "24976118" }, { "type": "pubmed", "citation": "Valentino MA, et al. \"Central and peripheral molecular targets for antiobesity pharmacotherapy.\" Clin Pharmacol Ther, 2010;87(6):652-62. PMID: 20445536.", "pmid": "20445536" }, { "type": "other", "citation": "U.S. Food and Drug Administration. Certain bulk drug substances for use in compounding that may present significant safety risks (AOD-9604, among nominations withdrawn). Content current as of April 22, 2026; read September 27, 2026." } ], "interactionCoverage": "none-found", "related": [ "tesamorelin", "cjc-1295" ], "lastReviewed": "2026-09-27", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.2.3", "named": true, "wording": "AOD-9604", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Named as a growth hormone fragment, alongside hGH 176-191." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.2.3", "named": true, "wording": "AOD-9604", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Named as a growth hormone fragment, alongside hGH 176-191." } ], "moleculeClass": "peptide" }, { "id": "apelin", "name": "Apelin", "aliases": [ "APLN", "Apelin-13", "Apelin-36", "Pyr-Apelin-13" ], "tier": "mid", "category": "cardiovascular", "subcategory": "endogenous vasoactive peptide", "class": "A family of endogenous peptides (including apelin-36 and apelin-13) cut from a 77-residue preproprotein, acting as the natural ligand of the APJ receptor.", "tagline": "The natural ligand of the APJ receptor, discovered in 1998: in short human infusion studies it widened arteries through nitric oxide and, in kidney disease, lowered blood pressure and raised kidney blood flow. A research peptide; no apelin drug is approved.", "oneLiner": "An endogenous peptide ligand for the APJ receptor (a GPCR structurally related to the angiotensin II receptor), with inotropic, vasodilatory, and cardioprotective effects that functionally antagonize the RAAS system.", "sequence": "QRPRLSHKGPMPF (Apelin-13; pyroglutamyl form is most potent)", "molecularFormula": "C69H111N23O16S", "molecularWeight": 1550.8, "halfLife": { "value": null, "unit": null, "range": "Not reported in the abstracts read", "notes": "The earlier '~5 minutes (apelin-13)' had no source.", "source": { "type": "qualitative", "note": "a description with no figure; no half-life measurement is cited for it" } }, "fdaStatus": "research-only", "approvalDetails": "Not approved. Synthetic apelin analogs are in early clinical development for heart failure and pulmonary arterial hypertension.", "mechanism": "Agonist at the APJ receptor (Apelin receptor, a Gi/Gq-coupled GPCR). Increases cardiac contractility (positive inotrope) without hypertrophy, promotes vasodilation via endothelial NO release, opposes angiotensin II-mediated vasoconstriction and fibrosis, stimulates angiogenesis, and has glucose-lowering effects. ACE2 is both a processing enzyme and regulator of the apelin system.", "primaryUses": [ "Cardiovascular physiology research", "Heart failure therapeutic target", "Pulmonary hypertension research", "Metabolic syndrome studies" ], "typicalDose": { "range": null, "unit": null, "frequency": null, "route": null, "notes": "Research compound. No established therapeutic dosing." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "Chapman FA, et al. \"Cardiovascular and renal effects of apelin in chronic kidney disease: a randomised, double-blind, placebo-controlled, crossover study.\" Nat Commun, 2024;15(1):8387. PMID: 39402039.", "pmid": "39402039" }, { "type": "pubmed", "citation": "Japp AG, et al. \"Acute cardiovascular effects of apelin in humans: potential role in patients with chronic heart failure.\" Circulation, 2010;121(16):1818-27. PMID: 20385929.", "pmid": "20385929" }, { "type": "pubmed", "citation": "Japp AG, et al. \"Vascular effects of apelin in vivo in man.\" J Am Coll Cardiol, 2008;52(11):908-13. PMID: 18772060.", "pmid": "18772060" }, { "type": "pubmed", "citation": "Dalzell JR, et al. \"Do plasma concentrations of apelin predict prognosis in patients with advanced heart failure?.\" Biomark Med, 2014;8(6):807-13. PMID: 25224937.", "pmid": "25224937" }, { "type": "pubmed", "citation": "Vinel C, et al. \"The exerkine apelin reverses age-associated sarcopenia.\" Nat Med, 2018;24(9):1360-1371. PMID: 30061698.", "pmid": "30061698" }, { "type": "pubmed", "citation": "Gao S, et al. \"Therapeutic potential of apelin and Elabela in cardiovascular disease.\" Biomed Pharmacother, 2023;166:115268. PMID: 37562237.", "pmid": "37562237" }, { "type": "pubmed", "citation": "Tatemoto K, et al. \"Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor.\" Biochem Biophys Res Commun, 1998;251(2):471-6. PMID: 9792798.", "pmid": "9792798" }, { "type": "fda", "citation": "FDA. Drugs@FDA (openFDA): no application for apelin. Read September 30, 2026." }, { "type": "other", "citation": "European Medicines Agency. Medicines register: no entry for apelin. Read September 30, 2026." } ], "interactionCoverage": "unreviewed", "related": [ "angiotensin-ii", "bnp", "anp" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-20", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "apitegromab", "name": "Apitegromab", "aliases": [ "SRK-015" ], "tier": "stub", "category": "pipeline", "subcategory": "anti-pro/latent myostatin monoclonal antibody", "class": "A fully human monoclonal antibody selective for the pro- and latent forms of myostatin, developed by Scholar Rock.", "tagline": "⚠ Monoclonal antibody, not a peptide. Scholar Rock's antibody against the proforms of myostatin, FDA-approved on September 11, 2026 as Isembyld for spinal muscular atrophy in patients 2 and older already on an SMN2-targeted treatment.", "oneLiner": "A fully human monoclonal antibody developed by Scholar Rock that selectively targets the pro- and latent forms of myostatin rather than the active mature ligand, preserving myostatin activity in non-target tissues. FDA approved it as Isembyld (apitegromab-mstn) on September 11, 2026, for spinal muscular atrophy in patients 2 years and older already receiving an SMN2-targeted treatment.", "sequence": null, "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": "weeks", "range": "Fc-mediated; weeks", "notes": "Long half-life typical of therapeutic antibodies." }, "fdaStatus": "approved", "approvalDetails": "FDA-approved September 11, 2026 as ISEMBYLD (apitegromab-mstn; Scholar Rock; BLA 761463) for spinal muscular atrophy in adults and children 2 years and older receiving an SMN2-targeted treatment; 10 mg/kg intravenously every 4 weeks; warning for fractures (Drugs@FDA; label, DailyMed version of September 17, 2026).", "mechanism": "Binds the N-terminal prodomain of myostatin on its pro- and latent forms, preventing activation to the mature active ligand. Because the antibody does not bind the processed active myostatin already in circulation at physiological levels in other tissues, the mechanism is claimed to be more tissue-selective than mature-myostatin or receptor-level blockade, reducing off-target effects on other GDF/activin pathway members.", "primaryUses": [ "Spinal muscular atrophy (Phase 3 positive; BLA preparation)", "Research interest in obesity muscle-sparing adjunct positioning" ], "typicalDose": { "range": "10–20", "unit": "mg/kg", "frequency": "every 4 weeks", "route": "intravenous", "notes": "SAPPHIRE protocol dosed IV every 4 weeks as an adjunct to SMN-targeted therapy." }, "evidenceLevel": "high", "sources": [ { "type": "manufacturer", "citation": "Scholar Rock. \"SAPPHIRE Phase 3 topline results for apitegromab in spinal muscular atrophy,\" corporate press release, October 2024." }, { "type": "clinical-trial", "citation": "ClinicalTrials.gov identifier for the SAPPHIRE Phase 3 trial in SMA." }, { "type": "fda-pi", "citation": "Scholar Rock, Inc. ISEMBYLD (apitegromab-mstn) injection, US prescribing information: spinal muscular atrophy in patients 2 years and older receiving an SMN2-targeted treatment; 10 mg/kg IV every 4 weeks; warning: fractures. DailyMed version of September 17, 2026, read September 30, 2026." }, { "type": "fda", "citation": "FDA. Drugs@FDA (openFDA), BLA 761463: ISEMBYLD (apitegromab-mstn), Scholar Rock; original approval September 11, 2026. Read September 30, 2026." } ], "interactionCoverage": "none-found", "related": [ "bimagrumab", "trevogrumab", "taldefgrobep-alfa" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S4.3", "named": true, "wording": "apitegromab", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S4.3", "named": true, "wording": "apitegromab", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "antibody", "moleculeClassBasis": "monoclonal antibody" }, { "id": "apraglutide", "name": "Apraglutide", "aliases": [ "FE 203799", "apraglutide acetate" ], "tier": "stub", "category": "pipeline", "subcategory": "long-acting GLP-2 analog (NDA submitted)", "class": "A long-acting GLP-2 analog with structural modifications for albumin binding and protease resistance, originated by Ferring and developed by Ironwood Pharmaceuticals.", "tagline": "Ironwood's weekly GLP-2 analog for short-bowel syndrome — STARS Phase 3 positive (2024), NDA submitted to FDA 2025; potentially the first once-weekly SBS therapy and a meaningful improvement over teduglutide's daily dosing.", "oneLiner": "A long-acting GLP-2 analog originated by Ferring and in-licensed by Ironwood Pharmaceuticals — STARS Phase 3 in adult short-bowel syndrome reported positive topline results in 2024 (reduction in weekly PN volume, with significantly higher rates of PN independence than placebo at 24 weeks); NDA submitted to FDA in 2025 with potential for approval 2026, offering once-weekly dosing that would substantially reduce injection burden vs daily teduglutide.", "sequence": "GLP-2 analog with protease-resistance and albumin-binding modifications", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": "hours", "range": "~27 hours", "notes": "Supports once-weekly dosing." }, "fdaStatus": "in-development", "approvalDetails": "Not yet approved. STARS Phase 3 in SBS completed 2024 with positive topline; NDA submitted 2025.", "mechanism": "GLP-2 receptor agonism with same intestinotrophic mechanism as teduglutide and glepaglutide. Albumin binding extends half-life.", "primaryUses": [ "Short-bowel syndrome (Phase 3 positive; NDA under review)" ], "typicalDose": { "range": "5", "unit": "mg", "frequency": "once weekly", "route": "subcutaneous", "notes": "STARS Phase 3 used 5 mg SC once weekly." }, "evidenceLevel": "high", "sources": [ { "type": "manufacturer", "citation": "Ironwood Pharmaceuticals. Press release: STARS Phase 3 topline positive results, 2024." }, { "type": "clinicaltrials", "citation": "ClinicalTrials.gov NCT04964986 (STARS Phase 3)." } ], "interactionCoverage": "none-found", "related": [ "teduglutide", "glepaglutide" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." } ], "moleculeClass": "peptide", "moleculeClassBasis": "GLP-2 analog" }, { "id": "ara-290", "name": "ARA-290", "aliases": [ "Cibinetide", "pHBSP" ], "tier": "full", "category": "healing", "subcategory": "erythropoietin-derived peptide", "class": "Synthetic 11-amino-acid peptide derived from the helix-B surface of erythropoietin (EPO), binding the tissue-protective heteromeric EPOR/βcR receptor without erythropoietic activity.", "tagline": "An 11-amino-acid EPO-derived peptide studied for neuropathic pain and tissue protection, without the red-cell-stimulating effects of full erythropoietin.", "oneLiner": "A synthetic peptide mimetic of erythropoietin's tissue-protective domain that activates the innate-repair heteromeric receptor (EPOR/βcR) selectively — producing anti-inflammatory and neuroprotective effects without erythropoiesis.", "sequence": "pGlu-EQLERALNSS (11 residues; N-terminal pyroglutamate; the aqueous face of erythropoietin's helix B)", "molecularFormula": "C51H84N16O21", "molecularWeight": 1257.3, "halfLife": { "value": null, "unit": null, "range": "Short; no human value in the published abstracts", "notes": "The literature describes its half-life as short; the earlier dataset figure (~2 minutes) had no source and was removed." }, "fdaStatus": "clinical-trials", "approvalDetails": "Investigational; not approved anywhere. Drugs@FDA holds no application for cibinetide and EMA's register of centrally authorised medicines has no entry (both read September 30, 2026). Phase 2 trials in sarcoidosis-associated small-fibre neuropathy, type 2 diabetes with neuropathy and diabetic macular oedema were co-authored by staff of Araim Pharmaceuticals (New York).", "mechanism": "Agonist at the innate repair receptor, the heteromeric complex of the erythropoietin receptor and the β-common receptor (CD131), designed from the aqueous face of EPO's helix B. In animal studies it reduced inflammatory signalling (CD131- and JAK2-dependent inhibition of NF-κB p65 in macrophages), neuronal apoptosis after stroke and renal injury after ischaemia, and inhibited the TRPV1 pain channel, without stimulating erythropoiesis, which runs through EPO-receptor homodimers.", "primaryUses": [ "Sarcoidosis-associated small-fibre neuropathy (phase 2)", "Painful neuropathy in type 2 diabetes (phase 2)", "Diabetic macular oedema (phase 2; no effect on vision or retinal thickness)", "Tissue protection and inflammation (animal research)" ], "typicalDose": { "range": "4", "unit": "mg", "frequency": "daily (trial dose)", "route": "subcutaneous", "notes": "Trial doses only: 2 mg IV three times weekly for 4 weeks (sarcoidosis pilot); 1, 4 or 8 mg SC daily for 28 days (phase 2b); 4 mg SC daily for 28 days (type 2 diabetes) or 12 weeks (macular oedema). No approved dose exists." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "Culver DA, et al. \"Cibinetide Improves Corneal Nerve Fiber Abundance in Patients With Sarcoidosis-Associated Small Nerve Fiber Loss and Neuropathic Pain.\" Invest Ophthalmol Vis Sci, 2017;58(6):BIO52-BIO60. PMID: 28475703.", "pmid": "28475703" }, { "type": "pubmed", "citation": "Heij L, et al. \"Safety and efficacy of ARA 290 in sarcoidosis patients with symptoms of small fiber neuropathy: a randomized, double-blind pilot study.\" Mol Med, 2012;18(1):1430-6. PMID: 23168581.", "pmid": "23168581" }, { "type": "pubmed", "citation": "Dahan A, et al. \"ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density.\" Mol Med, 2013;19(1):334-45. PMID: 24136731.", "pmid": "24136731" }, { "type": "pubmed", "citation": "Brines M, et al. \"ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes.\" Mol Med, 2015;20(1):658-66. PMID: 25387363.", "pmid": "25387363" }, { "type": "pubmed", "citation": "Lois N, et al. \"A Phase 2 Clinical Trial on the Use of Cibinetide for the Treatment of Diabetic Macular Edema.\" J Clin Med, 2020;9(7). PMID: 32674280.", "pmid": "32674280" }, { "type": "pubmed", "citation": "Cerit H, et al. \"Testing the antidepressant properties of the peptide ARA290 in a human neuropsychological model of drug action.\" Eur Neuropsychopharmacol, 2015;25(12):2289-99. PMID: 26431906.", "pmid": "26431906" }, { "type": "pubmed", "citation": "van Velzen M, et al. \"ARA 290 for treatment of small fiber neuropathy in sarcoidosis.\" Expert Opin Investig Drugs, 2014;23(4):541-50. PMID: 24555851.", "pmid": "24555851" }, { "type": "pubmed", "citation": "Wang RL, et al. \"Erythropoietin-derived peptide ARA290 mediates brain tissue protection through the β-common receptor in mice with cerebral ischemic stroke.\" CNS Neurosci Ther, 2024;30(3):e14676. PMID: 38488446.", "pmid": "38488446" }, { "type": "pubmed", "citation": "Nairz M, et al. \"Cibinetide dampens innate immune cell functions thus ameliorating the course of experimental colitis.\" Sci Rep, 2017;7(1):13012. PMID: 29026145.", "pmid": "29026145" }, { "type": "pubmed", "citation": "van Rijt WG, et al. \"ARA290, a non-erythropoietic EPO derivative, attenuates renal ischemia/reperfusion injury.\" J Transl Med, 2013;11:9. PMID: 23302512.", "pmid": "23302512" }, { "type": "pubmed", "citation": "Bitto A, et al. \"Activation of the EPOR-β common receptor complex by cibinetide ameliorates impaired wound healing in mice with genetic diabetes.\" Biochim Biophys Acta Mol Basis Dis, 2018;1864(2):632-639. PMID: 29223734.", "pmid": "29223734" }, { "type": "pubmed", "citation": "Zhang W, et al. \"ARA 290 relieves pathophysiological pain by targeting TRPV1 channel: Integration between immune system and nociception.\" Peptides, 2016;76:73-9. PMID: 26774587.", "pmid": "26774587" }, { "type": "pubmed", "citation": "Brines M, et al. \"Nonerythropoietic, tissue-protective peptides derived from the tertiary structure of erythropoietin.\" Proc Natl Acad Sci U S A, 2008;105(31):10925-30. PMID: 18676614.", "pmid": "18676614" }, { "type": "fda", "citation": "FDA. Drugs@FDA (openFDA): no application for cibinetide (ARA 290). Read September 30, 2026." }, { "type": "other", "citation": "European Medicines Agency. Medicines register (centrally authorised human medicines): no entry for cibinetide. Read September 30, 2026." } ], "interactionCoverage": "none-found", "related": [ "erythropoietin", "cerebrolysin", "thymosin-beta-4", "kpv" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.1.5", "named": false, "wording": "Innate repair receptor agonists", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "ARA-290 (cibinetide) is an EPO-derived peptide that activates the innate repair receptor, the class S2.1.5 names." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.1.5", "named": false, "wording": "Innate repair receptor agonists", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "ARA-290 (cibinetide) is an EPO-derived peptide that activates the innate repair receptor, the class S2.1.5 names." } ], "moleculeClass": "peptide" }, { "id": "argireline", "name": "Argireline", "aliases": [ "Acetyl Hexapeptide-3", "Acetyl Hexapeptide-8", "AH-8" ], "tier": "stub", "category": "cosmetic", "subcategory": "topical cosmetic peptide", "class": "A synthetic hexapeptide marketed as a topical cosmetic ingredient for the reduction of expression lines.", "tagline": "A cosmetic-industry hexapeptide marketed as \"topical Botox\" — reduces muscle contraction signaling at the neuromuscular junction; modest but documented effects on expression-line depth.", "oneLiner": "A synthetic acetylated hexapeptide derived from the N-terminal fragment of SNAP-25, marketed under the brand Argireline (Lipotec) as a topical cosmetic ingredient that modestly reduces neuromuscular acetylcholine release at the skin surface.", "sequence": "Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2", "molecularFormula": "C34H60N14O12S", "molecularWeight": 888.98, "halfLife": { "value": null, "unit": null, "range": "topical only", "notes": "Systemic absorption from topical cosmetic formulations is minimal." }, "fdaStatus": "research-only", "approvalDetails": "Not a drug. Widely used as an ingredient in cosmetic topical formulations. Not FDA-approved as a therapeutic; cosmetic use governed by cosmetic-ingredient regulations rather than drug approval.", "mechanism": "Competes with SNAP-25 for binding at the SNARE complex, modestly reducing vesicle docking and thereby acetylcholine release at the neuromuscular junction. The effect at topically achievable concentrations is much smaller than botulinum toxin but reproducible in placebo-controlled cosmetic studies of expression-line depth.", "primaryUses": [ "Topical cosmetic anti-aging formulations" ], "typicalDose": { "range": "5–10", "unit": "% (topical formulation)", "frequency": "daily topical application", "route": "topical", "notes": "Cosmetic concentrations; not used as an injectable." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "Blanes-Mira C, et al. \"A synthetic hexapeptide (Argireline) with antiwrinkle activity.\" Int J Cosmet Sci, 2002;24:303-310. PMID: 18498523.", "pmid": "18498523" }, { "type": "pubmed", "citation": "Wang Y, et al. \"The anti-wrinkle efficacy of argireline, a synthetic hexapeptide, in Chinese subjects: a randomized, placebo-controlled study.\" Am J Clin Dermatol, 2013;14:147-153. PMID: 23417317.", "pmid": "23417317" } ], "interactionCoverage": "unreviewed", "related": [ "matrixyl", "snap-8", "ghk-cu" ], "lastReviewed": "2026-04-18", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." } ], "moleculeClass": "peptide" }, { "id": "atosiban", "name": "Atosiban", "aliases": [ "Tractocile", "Antocin" ], "tier": "mid", "category": "sexual-health", "subcategory": "oxytocin receptor antagonist", "class": "Synthetic oxytocin and vasopressin V1a receptor antagonist used as a tocolytic for short-term suppression of preterm labor; not FDA-approved.", "tagline": "Ferring's Tractocile — an oxytocin-receptor antagonist used in Europe and elsewhere as a tocolytic for short-term suppression of preterm labor between 24 and 33 weeks' gestation. Approved by the EMA in 2000; the FDA declined to approve atosiban in 1998 citing a higher fetal/infant death rate in the <26-week subgroup of the pivotal trial.", "oneLiner": "A synthetic modified oxytocin peptide with competitive antagonist activity at both the oxytocin receptor (OXTR) and the vasopressin V1a receptor. Suppresses myometrial contractions by blocking OXTR-mediated calcium mobilization. Marketed in Europe, the UK, Australia, Canada, and other regions as Tractocile (Ferring Pharmaceuticals) — a first-line tocolytic option for short-term suppression (48 hours) of preterm labor between 24+0 and 33+6 weeks. Never FDA-approved: the US pivotal trial (Romero 2000) showed a higher rate of fetal/infant deaths in the atosiban arm concentrated in the <26-week stratum (where placebo-randomized women were more often treated with alternative tocolytics), and the FDA issued a non-approvable letter in 1998. No re-filing has occurred.", "sequence": "Mpa-D-Tyr(Et)-Ile-Thr-Asn-Cys-Pro-Orn-Gly-NH2 (cyclic)", "molecularFormula": "C43H67N11O12S2", "molecularWeight": 994.2, "halfLife": { "value": 1.7, "unit": "hours", "range": "initial 0.21 hours and terminal 1.7 hours after the infusion ends (EMA product information, section 5.2)", "source": { "type": "label", "ref": "Tractocile (atosiban) summary of product characteristics, sections 4.1, 4.2, 4.3, 4.8 and 5.2, European Medicines Agency product information (first authorisation January 20, 2000; read October 1, 2026)" } }, "fdaStatus": "not-approved-us", "approvalDetails": "Not approved in the US. Authorised in the EU as Tractocile (first authorisation January 20, 2000) to delay imminent preterm birth in adult women at 24 to 33 completed weeks who meet set criteria (EMA product information, read October 1, 2026).", "mechanism": "Competitive antagonism of OXTR on myometrial cells, blocking oxytocin-mediated phospholipase-C activation, IP3-mediated calcium release, and myometrial contraction. Also antagonizes the V1a vasopressin receptor, which co-participates in myometrial contractility. The 48-hour window of tocolytic efficacy is used primarily to enable antenatal corticosteroid administration and maternal transfer to a neonatal-capable center.", "primaryUses": [ "Short-term (48-hour) suppression of preterm labor between 24+0 and 33+6 weeks' gestation (ex-US, to facilitate antenatal corticosteroid course and maternal transfer)" ], "typicalDose": { "range": "6.75 mg bolus, then 300 then 100 micrograms/min", "unit": "mg", "frequency": "a single intravenous course of up to 48 hours", "route": "intravenous", "notes": "Tractocile (EU): a 6.75 mg intravenous bolus, then 300 micrograms/min for 3 hours, then 100 micrograms/min up to 45 hours; total course no more than 48 hours and preferably no more than 330.75 mg. Not approved in the US." }, "evidenceLevel": "high", "sources": [ { "type": "other", "citation": "Tractocile (atosiban) summary of product characteristics, sections 4.1, 4.2, 4.3, 4.8 and 5.2, European Medicines Agency product information (first authorisation January 20, 2000; read October 1, 2026)." }, { "type": "pubmed", "citation": "Romero R, et al. \"An oxytocin receptor antagonist (atosiban) in the treatment of preterm labor: a randomized, double-blind, placebo-controlled trial with tocolytic rescue.\" Am J Obstet Gynecol, 2000;182(5):1173-83. PMID: 10819855.", "pmid": "10819855" }, { "type": "pubmed", "citation": " \"Treatment of preterm labor with the oxytocin antagonist atosiban: a double-blind, randomized, controlled comparison with salbutamol.\" Eur J Obstet Gynecol Reprod Biol, 2001;98(2):177-85. PMID: 11574128.", "pmid": "11574128" }, { "type": "pubmed", "citation": "van Winden TMS, et al. \"Tocolysis with nifedipine versus atosiban and perinatal outcome: an individual participant data meta-analysis.\" BMC Pregnancy Childbirth, 2022;22(1):567. PMID: 35840927.", "pmid": "35840927" }, { "type": "pubmed", "citation": "van der Windt LI, et al. \"Atosiban versus placebo for threatened preterm birth (APOSTEL 8): a multicentre, randomised controlled trial.\" Lancet, 2025;405(10483):1004-1013. PMID: 40049187.", "pmid": "40049187" }, { "type": "pubmed", "citation": "Flenady V, et al. \"Oxytocin receptor antagonists for inhibiting preterm labour.\" Cochrane Database Syst Rev, 2014;2014(6):CD004452. PMID: 24903678.", "pmid": "24903678" } ], "interactionCoverage": "none-found", "related": [ "oxytocin", "carbetocin" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": "EU (EMA), UK, Canada, Australia", "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "azd6234", "name": "AZD6234", "aliases": [ "AZD-6234" ], "tier": "stub", "category": "pipeline", "subcategory": "amylin analog (Phase 2)", "class": "A long-acting amylin analog peptide developed by AstraZeneca.", "tagline": "AstraZeneca's long-acting amylin analog — Phase 2 in obesity (2024) — part of AZ's entry into the GLP-1-adjacent obesity space alongside ECC5004; analogous in mechanism to cagrilintide.", "oneLiner": "A long-acting amylin analog peptide in Phase 2 development by AstraZeneca for obesity; mechanistically comparable to cagrilintide and petrelintide, targeting amylin receptors (hybrids of the calcitonin receptor with RAMP1/2/3) to drive satiety and slow gastric emptying independently of GLP-1 agonism.", "sequence": null, "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": "days", "range": "supports weekly dosing", "notes": "Long-acting by design." }, "fdaStatus": "clinical-trials", "approvalDetails": "Not approved. Phase 2 in obesity initiated 2024.", "mechanism": "Amylin receptor agonism (calcitonin receptor / RAMP1/2/3 heterodimers) — drives satiety via area postrema and hypothalamic circuits, slows gastric emptying, and suppresses postprandial glucagon. Intended for combination with GLP-1 RAs (the cagrisema / MariTide paradigm).", "primaryUses": [ "Obesity (Phase 2)" ], "typicalDose": { "range": null, "unit": null, "frequency": "once weekly", "route": "subcutaneous", "notes": "Phase 2 doses not publicly finalized." }, "evidenceLevel": "low", "sources": [ { "type": "manufacturer", "citation": "AstraZeneca pipeline page — AZD6234 Phase 2 amylin analog." }, { "type": "clinicaltrials", "citation": "ClinicalTrials.gov — AZD6234 Phase 2 obesity study." } ], "interactionCoverage": "none-found", "related": [ "cagrilintide", "petrelintide", "cagrisema" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." } ], "moleculeClass": "peptide" }, { "id": "bacitracin", "name": "Bacitracin", "aliases": [ "Bacitracin Zinc" ], "tier": "mid", "category": "immune", "subcategory": "polypeptide antibiotic", "class": "A mixture of cyclic polypeptide antibiotics produced by Bacillus subtilis and Bacillus licheniformis, used primarily as a topical antibiotic.", "tagline": "The topical first-aid antibiotic — one of the most widely used over-the-counter peptide antibiotics, found in virtually every household first-aid kit.", "oneLiner": "A cyclic polypeptide antibiotic that inhibits bacterial cell wall synthesis by sequestering the C55-isoprenyl pyrophosphate lipid carrier, preventing peptidoglycan recycling — used almost exclusively topically due to nephrotoxicity.", "sequence": "Cyclic dodecapeptide (bacitracin A is the primary component)", "molecularFormula": "C66H103N17O16S", "molecularWeight": 1422.7, "halfLife": { "value": null, "unit": null, "range": "not applicable to the topical product; systemic use was abandoned for kidney toxicity", "source": { "type": "none", "note": "searched PubMed on October 1, 2026; no human half-life figure in the sources read" } }, "fdaStatus": "approved", "approvalDetails": "Marketed over the counter as a topical antibiotic, usually combined with neomycin and polymyxin B; the Drug Facts label read on DailyMed on October 1, 2026 covers first aid for minor cuts, scrapes and burns. Injectable bacitracin is no longer marketed because of kidney toxicity.", "mechanism": "Binds to C55-isoprenyl pyrophosphate (undecaprenyl pyrophosphate), the lipid carrier that shuttles peptidoglycan building blocks across the bacterial membrane. By sequestering this carrier, bacitracin prevents its dephosphorylation and recycling, halting cell wall synthesis. Active against gram-positive organisms and some gram-negatives.", "primaryUses": [ "Topical wound infection prophylaxis", "Minor cuts, scrapes, and burns", "Ophthalmic infections (bacitracin ophthalmic ointment)", "Surgical irrigation (historically)" ], "typicalDose": { "range": null, "unit": null, "frequency": "one to three times daily", "route": "topical", "notes": "Drug Facts label for the over-the-counter ointment: clean the area, apply an amount equal to the surface area of a fingertip, one to three times a day, and it may be covered with a sterile bandage. Under two years of age, ask a doctor." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Over-the-counter triple antibiotic ointment (bacitracin zinc, neomycin sulfate, polymyxin B sulfate) Drug Facts label, Uses and Directions (DailyMed, read October 1, 2026)." }, { "type": "pubmed", "citation": "Soto NE, et al. \"Bacitracin versus mupirocin for Staphylococcus aureus nasal colonization.\" Infect Control Hosp Epidemiol, 1999;20(5):351-3. PMID: 10349956.", "pmid": "10349956" }, { "type": "pubmed", "citation": "Saryan JA, et al. \"Anaphylaxis to topical bacitracin zinc ointment.\" Am J Emerg Med, 1998;16(5):512-3. PMID: 9725969.", "pmid": "9725969" }, { "type": "pubmed", "citation": "Vale MA, et al. \"Bacitracin-induced anaphylaxis.\" Arch Dermatol, 1978;114(5):800. PMID: 348120.", "pmid": "348120" }, { "type": "pubmed", "citation": "Andrews BJ, et al. \"Chemotherapy for giardiasis: randomized clinical trial of bacitracin, bacitracin zinc, and a combination of bacitracin zinc with neomycin.\" Am J Trop Med Hyg, 1995;52(4):318-21. PMID: 7741168.", "pmid": "7741168" }, { "type": "pubmed", "citation": "Walton MA, et al. \"The efficacy of Polysporin First Aid Antibiotic Spray (polymyxin B sulfate and bacitracin zinc) against clinical burn wound isolates.\" J Burn Care Rehabil, 1991;12(2):116-9. PMID: 2050717.", "pmid": "2050717" }, { "type": "pubmed", "citation": "Stone KJ, et al. \"Mechanism of action of bacitracin: complexation with metal ion and C 55 -isoprenyl pyrophosphate.\" Proc Natl Acad Sci U S A, 1971;68(12):3223-7. PMID: 4332017.", "pmid": "4332017" } ], "interactionCoverage": "none-found", "related": [ "polymyxin-b", "daptomycin", "ll-37" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-20", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "blend", "moleculeClassBasis": "mixture of cyclic polypeptide" }, { "id": "beinaglutide", "name": "Beinaglutide", "aliases": [ "Benaglutide", "Benefit", "rhGLP-1(7-36)" ], "tier": "mid", "category": "metabolic", "subcategory": "short-acting native GLP-1", "class": "A recombinant form of native human GLP-1(7-36)-amide produced by Shanghai Benemae Pharmaceutical.", "tagline": "Recombinant human GLP-1 with the natural 30-amino-acid GLP-1(7-36) sequence, injected three times daily; used for type 2 diabetes in China, and in a 16-week phase 3 trial it cut weight by 6.0% against 2.4% on placebo. Not FDA- or EMA-approved.", "oneLiner": "A recombinant human GLP-1(7-36) amide — the native active peptide without sequence modification — produced by Shanghai Benemae and approved by China's NMPA in 2016 for type 2 diabetes and in 2023 for adult obesity; the unmodified backbone gives it a very short half-life (requiring three-times-daily SC injection) but spares it the structural changes that drive immunogenicity and injection-site reactions in other GLP-1 agonists.", "sequence": "HAEGTFTSDVSSYLEGQAAKEFIAWLVKGR (human GLP-1(7-36); PubChem records a free C-terminal acid)", "molecularFormula": "C149H225N39O46", "molecularWeight": 3298.6, "halfLife": { "value": null, "unit": null, "range": "short; peak level 10 to 15 minutes after injection", "source": { "type": "pmid", "pmid": "39239660", "cite": "Lin P, et al. \"Pharmacokinetics and safety profiles of beinaglutide injection, a recombinant human GLP-1, in adults with overweight/obesity: results from a phase I clinical trial.\" Front Pharmacol, 2024;15:1433587. PMID: 39239660." } }, "fdaStatus": "not-approved-us", "approvalDetails": "Used for type 2 diabetes in China (described as widely used in a 2024 pharmacokinetic study, PMID 39239660); regulatory dates not verified. Not FDA-approved (no Drugs@FDA application) and not in EMA's register (both read September 30, 2026).", "mechanism": "GLP-1 receptor agonism using the native, unmodified human GLP-1(7-36) amide sequence. Because it lacks the DPP-4-resistance mutations of exenatide, liraglutide, semaglutide and similar analogs, beinaglutide has a plasma half-life of roughly 11 minutes and must be injected before each main meal. The short half-life does, however, mean it is essentially non-immunogenic.", "primaryUses": [ "Type 2 diabetes mellitus (China)", "Obesity / overweight (China — NMPA 2023)" ], "typicalDose": { "range": "0.1–0.2", "unit": "mg", "frequency": "three times daily (trial doses)", "route": "subcutaneous", "notes": "Trials used 0.1, 0.14 and 0.2 mg three times daily; the phase 3 weight trial used 0.2 mg." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "Chen K, et al. \"Beinaglutide for weight management in Chinese individuals with overweight or obesity: A phase 3 randomized controlled clinical study.\" Diabetes Obes Metab, 2024;26(2):690-698. PMID: 37945546.", "pmid": "37945546" }, { "type": "pubmed", "citation": "Gao L, et al. \"Comparison of Beinaglutide Versus Metformin for Weight Loss in Overweight and Obese Non-diabetic Patients.\" Exp Clin Endocrinol Diabetes, 2022;130(6):358-367. PMID: 34856624.", "pmid": "34856624" }, { "type": "pubmed", "citation": "Lin P, et al. \"Pharmacokinetics and safety profiles of beinaglutide injection, a recombinant human GLP-1, in adults with overweight/obesity: results from a phase I clinical trial.\" Front Pharmacol, 2024;15:1433587. PMID: 39239660.", "pmid": "39239660" }, { "type": "pubmed", "citation": "Liu X, et al. \"The efficacy and safety of beinaglutide alone or in combination with insulin glargine in Chinese patients with type 2 diabetes mellitus who are inadequately controlled with oral antihyperglycemic therapy: A multicenter, open-label, randomized trial.\" J Diabetes, 2023;16(2). PMID: 37864379.", "pmid": "37864379" }, { "type": "pubmed", "citation": "Poshtdar S, et al. \"The effects of Beinaglutide on obesity and related factors: a systematic review and meta-analysis of randomized controlled trials.\" Expert Rev Endocrinol Metab, 2025;20(4):307-316. PMID: 40214160.", "pmid": "40214160" }, { "type": "fda", "citation": "FDA. Drugs@FDA (openFDA): no application for beinaglutide. Read September 30, 2026." }, { "type": "other", "citation": "European Medicines Agency. Medicines register: no entry for beinaglutide. Read September 30, 2026." } ], "interactionCoverage": "none-found", "related": [ "liraglutide", "exenatide", "semaglutide" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": "China (NMPA)", "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "beta-endorphin", "name": "Beta-Endorphin", "aliases": [ "b-Endorphin", "b-EP", "Beta-EP", "Endorphin" ], "tier": "mid", "category": "cognitive", "subcategory": "Endogenous opioid peptide", "class": "Beta-endorphin is an endogenous opioid neuropeptide produced in the pituitary gland and hypothalamus. It is the body's most potent natural painkiller and the molecule behind the 'runner's high.'", "tagline": "The body's most potent endogenous painkiller — the 31-amino-acid opioid peptide behind the 'runner's high' and natural pain modulation.", "oneLiner": "A 31-amino-acid endogenous opioid peptide cleaved from proopiomelanocortin (POMC) that binds mu-opioid receptors with high affinity, producing analgesia, euphoria, and stress modulation — the most pharmacologically active of the endorphin family.", "sequence": "YGGFMTSEKSQTPLVTLFKNAIIKNAYKKGE", "molecularFormula": "C158H251N39O44S", "molecularWeight": 3465.0, "halfLife": { "value": null, "unit": null, "range": "not reported in the sources read", "source": { "type": "none", "note": "searched PubMed on October 1, 2026; no human half-life figure in the sources read" } }, "fdaStatus": "research-only", "approvalDetails": "Not approved as a drug; no application appears in Drugs@FDA (read October 1, 2026). It was given intravenously in small research studies around 1980.", "mechanism": "Cleaved from the C-terminal region of proopiomelanocortin (POMC) in the anterior pituitary and arcuate nucleus of the hypothalamus. Binds mu-opioid receptors (MOR) with highest affinity (Ki ~1 nM) and delta-opioid receptors with moderate affinity. MOR activation inhibits GABAergic interneurons in the ventral tegmental area, disinhibiting dopamine release and producing analgesia, euphoria, and anxiolysis. Also modulates immune function via opioid receptors on lymphocytes and macrophages.", "primaryUses": [ "Endogenous pain modulation (stress-induced analgesia)", "Exercise-induced euphoria ('runner's high')", "Research biomarker for pain sensitivity and addiction vulnerability", "Neuroimmune signaling research" ], "typicalDose": { "range": null, "unit": null, "frequency": null, "route": null, "notes": "Not a medicine. Given as a single intravenous 20 mg dose in a 1980 study in nine men (PMID 7387335)." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Sylvén C, et al. \"Beta-endorphin but not metenkephalin counteracts adenosine-provoked angina pectoris-like pain.\" Neuroreport, 1996;7(12):1982-4. PMID: 8905708.", "pmid": "8905708" }, { "type": "pubmed", "citation": "Berger PA, et al. \"beta-Endorphin and schizophrenia.\" Arch Gen Psychiatry, 1980;37(6):635-40. PMID: 7387335.", "pmid": "7387335" }, { "type": "pubmed", "citation": "Pfefferbaum A, et al. \"Human EEG response to beta-endorphin.\" Psychiatry Res, 1979;1(1):83-8. PMID: 298341.", "pmid": "298341" }, { "type": "pubmed", "citation": "Cleeland CS, et al. \"CSF beta-endorphin and the severity of pain.\" Neurology, 1984;34(3):378-80. PMID: 6322046.", "pmid": "6322046" }, { "type": "pubmed", "citation": "Krantz DE, et al. \"Dexamethasone suppresses beta-endorphin in humans.\" Psychoneuroendocrinology, 1985;10(2):211-4. PMID: 2930864.", "pmid": "2930864" }, { "type": "pubmed", "citation": "Altınayak SÖ, et al. \"The effects of conventional, warm and cold acupressure on the pain perceptions and beta-endorphin plasma levels of primiparous women in labor: A randomized controlled trial.\" Explore (NY), 2022;18(5):545-550. PMID: 35193802.", "pmid": "35193802" }, { "type": "pubmed", "citation": "Sprouse-Blum AS, et al. \"Understanding endorphins and their importance in pain management.\" Hawaii Med J, 2010;69(3):70-1. PMID: 20397507.", "pmid": "20397507" }, { "type": "pubmed", "citation": "Boecker H, et al. \"The runner's high: opioidergic mechanisms in the human brain.\" Cereb Cortex, 2008;18(11):2523-31. PMID: 18296435.", "pmid": "18296435" } ], "interactionCoverage": "unreviewed", "related": [ "enkephalin", "dynorphin", "dermorphin", "dsip" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-21", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "bimagrumab", "name": "Bimagrumab", "aliases": [ "BYM338", "ActRII antibody" ], "tier": "mid", "category": "pipeline", "subcategory": "activin type II receptor antibody (muscle-sparing adjunct)", "class": "A fully human monoclonal antibody against activin type II receptors (ActRIIA and ActRIIB), acting as a receptor-level myostatin/activin blocker.", "tagline": "The activin receptor antibody that adds muscle and removes fat: failed in a muscle disease, now paired with semaglutide for obesity.", "oneLiner": "A monoclonal antibody blocking activin type II receptors, the pathway myostatin uses to limit muscle growth, given by infusion.", "sequence": null, "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": "weeks", "range": "Fc-mediated; weeks", "notes": "Long half-life typical of full-length therapeutic antibodies; dosing is monthly or less frequent.", "source": { "type": "qualitative", "note": "a description with no figure; no half-life measurement is cited for it" } }, "fdaStatus": "clinical-trials", "approvalDetails": "Not approved anywhere. Phase 2 trials in obesity, type 2 diabetes and sarcopenia; the RESILIENT trial in inclusion body myositis did not meet its walking endpoint.", "mechanism": "Binds ActRIIA and ActRIIB with high affinity, blocking signaling from myostatin (GDF-8), activin A, and related TGF-β family ligands at the receptor level. Unlike the ligand-trap approach of ACE-031 (soluble ActRIIB-Fc), bimagrumab blocks the receptor itself rather than sequestering ligands — this receptor-specific blockade appears to avoid the BMP9/BMP10-related vascular toxicities that stopped ACE-031. The resulting myostatin pathway inhibition drives muscle protein synthesis and blunts the lean-mass loss that occurs with caloric restriction.", "primaryUses": [ "Obesity, with or without semaglutide (phase 2)", "Sarcopenia (phase 2)" ], "typicalDose": { "range": "10–30", "unit": "mg/kg", "frequency": "monthly (IV) in Phase 2 trials", "route": "intravenous (current); SC under investigation", "notes": "BELIEVE trial dosed IV at weeks 4, 16, 28, and 40. A subcutaneous formulation is in development." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "Heymsfield SB, et al. \"Bimagrumab plus semaglutide alone or in combination for the treatment of obesity: a randomized phase 2 trial.\" Nat Med, 2026;32(3):869-882. PMID: 41772149.", "pmid": "41772149" }, { "type": "pubmed", "citation": "Heymsfield SB, et al. \"Effect of Bimagrumab vs Placebo on Body Fat Mass Among Adults With Type 2 Diabetes and Obesity: A Phase 2 Randomized Clinical Trial.\" JAMA Netw Open, 2021;4(1):e2033457. PMID: 33439265.", "pmid": "33439265" }, { "type": "pubmed", "citation": "Rooks D, et al. \"Treatment of Sarcopenia with Bimagrumab: Results from a Phase II, Randomized, Controlled, Proof-of-Concept Study.\" J Am Geriatr Soc, 2017;65(9):1988-1995. PMID: 28653345.", "pmid": "28653345" }, { "type": "pubmed", "citation": "Hanna MG, et al. \"Safety and efficacy of intravenous bimagrumab in inclusion body myositis (RESILIENT): a randomised, double-blind, placebo-controlled phase 2b trial.\" Lancet Neurol, 2019;18(9):834-844. PMID: 31397289.", "pmid": "31397289" } ], "interactionCoverage": "partial", "related": [ "ace-031", "follistatin-344", "semaglutide", "tirzepatide" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S4.3", "named": true, "wording": "bimagrumab", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S4.3", "named": true, "wording": "bimagrumab", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "antibody", "moleculeClassBasis": "monoclonal antibody" }, { "id": "bioactive-food-peptides", "name": "Bioactive Food Peptides", "aliases": [ "Food-Derived Peptides", "Dietary Bioactive Peptides", "Casein Peptides", "Whey Peptides" ], "tier": "stub", "category": "research", "subcategory": "food science / nutraceutical", "class": "A broad category of biologically active peptide fragments released during digestion or fermentation of dietary proteins (casein, whey, egg, soy, fish, plant), with antihypertensive, antioxidant, antimicrobial, opioid, and immunomodulatory activities.", "tagline": "The hidden pharmacology of food — bioactive peptide fragments released during digestion of milk, meat, fish, and plant proteins, including casomorphins, lactokinins, and ACE-inhibitory peptides.", "oneLiner": "Peptide fragments (typically 2–20 amino acids) encrypted within food protein sequences and liberated by digestive enzymes or fermentation, some with documented blood-pressure-lowering, opioid, or immune-modulating effects at physiological concentrations.", "sequence": "Various; e.g., VPP and IPP (casein-derived ACE inhibitors), β-casomorphin-7 (opioid peptide from casein)", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": null, "range": "Variable — dipeptides and tripeptides absorbed intact via PepT1; larger peptides degraded", "notes": "Oral bioavailability depends on peptide size and protease resistance. Di- and tripeptides can reach systemic circulation intact." }, "fdaStatus": "supplement", "approvalDetails": "Individual products (e.g., Lactobacillus-fermented milk with VPP/IPP) approved as FOSHU (Foods for Specified Health Uses) in Japan. Not FDA-approved as drugs. Some marketed as dietary supplements.", "mechanism": "Mechanism varies by peptide class: (1) ACE-inhibitory peptides (VPP, IPP from casein) lower blood pressure by inhibiting angiotensin-converting enzyme; (2) Casomorphins (β-casomorphin-7) are μ-opioid receptor agonists; (3) Immunopeptides (lactoferricin) have antimicrobial and immunomodulatory effects; (4) Antioxidant peptides scavenge free radicals via His, Trp, Tyr, Cys, and Met residues.", "primaryUses": [ "Functional food research", "Antihypertensive nutraceuticals", "Sports nutrition (whey peptides)", "Gut health and immune modulation" ], "typicalDose": { "range": null, "unit": null, "frequency": null, "route": "oral (dietary)", "notes": "Varies widely. ACE-inhibitory milk peptides: ~3–5 mg VPP+IPP/day. Whey protein hydrolysate: 20–40 g/day. Context-dependent." }, "evidenceLevel": "medium", "sources": [ { "type": "review", "citation": "Korhonen H, Pihlanto A. \"Bioactive peptides: production and functionality.\" Int Dairy J, 2006;16:945-960." }, { "type": "review", "citation": "Cicero AFG, et al. \"Blood pressure lowering effect of lactotripeptides assumed as functional foods: a meta-analysis of current available clinical trials.\" J Hum Hypertens, 2011;25:425-436. PMID: 20811398.", "pmid": "20811398" } ], "interactionCoverage": "unreviewed", "related": [ "collagen-peptides", "carnosine", "lactoferricin" ], "lastReviewed": "2026-04-20", "publishedAt": "2026-04-20", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "A food or supplement ingredient, not a drug; S0 is written for pharmacological substances. Supplements carry a separate risk: contamination with prohibited substances." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "A food or supplement ingredient, not a drug; S0 is written for pharmacological substances. Supplements carry a separate risk: contamination with prohibited substances." } ], "moleculeClass": "peptide" }, { "id": "biotinoyl-tripeptide-1", "name": "Biotinoyl Tripeptide-1", "aliases": [ "Biotinyl-GHK", "Procapil component" ], "tier": "stub", "category": "cosmetic", "subcategory": "Hair growth cosmeceutical peptide", "class": "Biotinoyl Tripeptide-1 is a biotin-modified GHK peptide primarily used in hair care — combining GHK's tissue-regenerative signal with biotin's hair growth support.", "tagline": "A biotin-peptide hybrid for hair loss — combining GHK's tissue repair signaling with biotin to strengthen follicles and reduce thinning.", "oneLiner": "A conjugate of biotin (vitamin B7) with the tripeptide GHK that strengthens hair follicle anchoring, reduces DHT-mediated miniaturization, and improves hair matrix cell metabolism — the peptide component of the popular hair loss formulation Procapil.", "sequence": "Biotinyl-GHK (biotin-Gly-His-Lys)", "molecularFormula": "C22H36N6O5S", "molecularWeight": 496.62, "halfLife": { "value": null, "unit": null, "range": "Hours (topical)", "notes": "Applied topically to scalp." }, "fdaStatus": "supplement", "approvalDetails": "Cosmetic/hair care ingredient. Key component of Procapil (Biotinoyl Tripeptide-1 + Oleanolic acid + Apigenin) by Sederma/Croda.", "mechanism": "The GHK motif stimulates extracellular matrix production in the dermal papilla. Biotin conjugation enhances metabolic activity of hair matrix keratinocytes. In Procapil, works synergistically with oleanolic acid (5-alpha-reductase inhibitor) and apigenin (vasodilator).", "primaryUses": [ "Anti-hair-loss scalp treatments (as Procapil)", "Strengthening follicle anchoring", "Hair growth serums and shampoos" ], "typicalDose": { "range": "1-3", "unit": "% Procapil in formulation", "frequency": "once daily", "route": "topical (scalp)", "notes": "Results typically visible after 3-6 months." }, "evidenceLevel": "low", "sources": [ { "type": "review", "citation": "Kapoor R, et al. \"Peptides in dermatology: a review.\" Indian Dermatol Online J. 2020;11(5):721-728." } ], "interactionCoverage": "none-found", "related": [ "ghk-cu", "pal-ghk", "palmitoyl-pentapeptide-4" ], "lastReviewed": "2026-04-21", "publishedAt": "2026-04-21", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." } ], "moleculeClass": "peptide" }, { "id": "bivalirudin", "name": "Bivalirudin", "aliases": [ "Angiomax", "Angiox", "Hirulog", "BG8967" ], "tier": "full", "category": "cardiovascular", "subcategory": "Direct thrombin inhibitor (bivalent)", "class": "A rationally-designed synthetic 20-amino-acid bivalent peptide analog of hirudin — the natural thrombin inhibitor from the medicinal leech Hirudo medicinalis — engineered to bind both the catalytic site and the fibrinogen-binding exosite of thrombin while being slowly cleaved by thrombin itself for predictable pharmacokinetics.", "tagline": "Angiomax — the workhorse direct thrombin inhibitor for percutaneous coronary intervention. FDA-approved December 2000 (The Medicines Company, now Sandoz); the first synthetic peptide DTI to achieve broad PCI adoption. REPLACE-2, ACUITY, and HORIZONS-AMI trials established the anticoagulant profile; subsequent MATRIX trial outcomes shifted practice in some populations back toward heparin.", "oneLiner": "A synthetic bivalent direct thrombin inhibitor rationally designed from structural studies of hirudin. The 20-residue peptide combines a hirudin-derived C-terminal dodecapeptide (that binds thrombin's anion-binding exosite 1, the fibrinogen-binding site) with an N-terminal D-Phe-Pro-Arg-Pro tetrapeptide (that binds thrombin's catalytic site), connected by a tetraglycine spacer. Unlike hirudin, bivalirudin binding to thrombin is transient because thrombin itself slowly cleaves the Arg3-Pro4 bond, releasing the N-terminal tetrapeptide and restoring thrombin catalytic activity — this gives the drug a predictable ~25-minute plasma half-life and reduces bleeding risk relative to irreversible DTIs. FDA-approved December 15, 2000 as Angiomax® by The Medicines Company (later acquired by Novartis in 2020; now Sandoz under the 2023 Novartis Sandoz spin-off) for use with aspirin in patients undergoing percutaneous coronary intervention. Label expanded 2005 (REPLACE-2) for broader PCI use and for patients with heparin-induced thrombocytopenia (ATBAT). Subsequently 2015 MATRIX and other trials triggered practice-pattern shifts in which bivalirudin's advantage over heparin narrowed; it remains a mainstay in HIT and in bleeding-risk PCI populations.", "sequence": "D-Phe-Pro-Arg-Pro-Gly-Gly-Gly-Gly-Asn-Gly-Asp-Phe-Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu", "molecularFormula": "C98H138N24O33", "molecularWeight": 2180.29, "halfLife": { "value": 25, "unit": "minutes", "range": "~25 minutes (normal renal function); prolonged in renal impairment", "notes": "Cleared by proteolytic degradation plus ~20% renal excretion; half-life extends to 57 minutes in severe renal impairment and several hours in dialysis patients. Hemodialyzable." }, "fdaStatus": "approved", "approvalDetails": "FDA-approved December 15, 2000 (Angiomax®, The Medicines Company, NDA 20873) as an anticoagulant for patients with unstable angina undergoing percutaneous transluminal coronary angioplasty, in conjunction with aspirin. Label expanded 2005 for use with or without GP IIb/IIIa inhibition in PCI (post-REPLACE-2). Further label expansion for heparin-induced thrombocytopenia (HIT) with or without thrombosis undergoing PCI (post-ATBAT). The Medicines Company was acquired by Novartis in 2020; Angiomax is now part of Sandoz (Novartis generics spin-off, 2023). Multiple generic bivalirudin products available since patent expiration.", "mechanism": "Bivalent direct thrombin inhibitor. The C-terminal hirudin-derived dodecapeptide (residues 9–20) occupies thrombin's exosite 1 (fibrinogen-binding site), preventing substrate recognition. The N-terminal D-Phe-Pro-Arg-Pro tetrapeptide (residues 1–4) occupies thrombin's active site, blocking catalytic activity. The tetraglycine linker allows both ends to engage simultaneously, producing high-affinity bivalent binding. Crucially, the Arg3-Pro4 peptide bond is slowly hydrolyzed by bound thrombin itself — a \"self-destructing\" inhibitor — which releases the N-terminal tetrapeptide and restores catalytic activity at a kinetically predictable rate. This self-limiting mechanism gives bivalirudin a much more predictable pharmacokinetic profile than irreversible DTIs and contributes to its lower bleeding risk. Bivalirudin inhibits both free and clot-bound thrombin (unlike heparin, which only inhibits free thrombin via antithrombin). No dependence on antithrombin; no risk of heparin-induced thrombocytopenia.", "primaryUses": [ "Anticoagulation during percutaneous coronary intervention (FDA-approved)", "PCI in patients with heparin-induced thrombocytopenia (FDA-approved)", "PCI in patients at high risk of bleeding (common off-label / guideline-supported indication)" ], "typicalDose": { "range": "0.75 mg/kg IV bolus followed by 1.75 mg/kg/h infusion for duration of PCI", "unit": "mg/kg and mg/kg/h", "frequency": "bolus + infusion for procedure duration", "route": "intravenous", "notes": "Dose reduction required in severe renal impairment (CrCl <30 mL/min: infusion reduced to 1 mg/kg/h). Hemodialyzable — can be removed if excessive anticoagulation. Monitoring by activated clotting time (ACT) optional during PCI." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Angiomax® (bivalirudin) for Injection Prescribing Information. The Medicines Company / Sandoz. Initial US approval December 15, 2000 (NDA 20873)." }, { "type": "clinical-trial", "citation": "Lincoff AM, Bittl JA, Harrington RA, et al. \"Bivalirudin and provisional glycoprotein IIb/IIIa blockade compared with heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary intervention (REPLACE-2).\" JAMA, 2003;289(7):853-863. PMID: 12588269.", "pmid": "12588269" }, { "type": "clinical-trial", "citation": "Stone GW, Witzenbichler B, Guagliumi G, et al. \"Bivalirudin during primary PCI in acute myocardial infarction (HORIZONS-AMI).\" N Engl J Med, 2008;358(21):2218-2230. PMID: 18499566.", "pmid": "18499566" }, { "type": "pubmed", "citation": "Stone GW, et al. \"Bivalirudin vs Heparin Anticoagulation in STEMI: Confirmation of the BRIGHT-4 Results.\" J Am Coll Cardiol, 2024;84(16):1512-1524. PMID: 39384262.", "pmid": "39384262" }, { "type": "pubmed", "citation": "Bikdeli B, et al. \"Bivalirudin Versus Heparin During PCI in NSTEMI: Individual Patient Data Meta-Analysis of Large Randomized Trials.\" Circulation, 2023;148(16):1207-1219. PMID: 37746717.", "pmid": "37746717" }, { "type": "pubmed", "citation": "Li Y, et al. \"Bivalirudin plus a high-dose infusion versus heparin monotherapy in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: a randomised trial.\" Lancet, 2022;400(10366):1847-1857. PMID: 36351459.", "pmid": "36351459" }, { "type": "pubmed", "citation": "Valgimigli M, et al. \"Bivalirudin or Unfractionated Heparin in Acute Coronary Syndromes.\" N Engl J Med, 2015;373(11):997-1009. PMID: 26324049.", "pmid": "26324049" }, { "type": "pubmed", "citation": "Shahzad A, et al. \"Unfractionated heparin versus bivalirudin in primary percutaneous coronary intervention (HEAT-PPCI): an open-label, single centre, randomised controlled trial.\" Lancet, 2014;384(9957):1849-1858. PMID: 25002178.", "pmid": "25002178" }, { "type": "pubmed", "citation": "Stone GW, et al. \"Bivalirudin for patients with acute coronary syndromes.\" N Engl J Med, 2006;355(21):2203-16. PMID: 17124018.", "pmid": "17124018" }, { "type": "pubmed", "citation": "Mahaffey KW, et al. \"The anticoagulant therapy with bivalirudin to assist in the performance of percutaneous coronary intervention in patients with heparin-induced thrombocytopenia (ATBAT) study: main results.\" J Invasive Cardiol, 2003;15(11):611-6. PMID: 14608128.", "pmid": "14608128" }, { "type": "pubmed", "citation": "Maraganore JM, et al. \"Design and characterization of hirulogs: a novel class of bivalent peptide inhibitors of thrombin.\" Biochemistry, 1990;29(30):7095-101. PMID: 2223763.", "pmid": "2223763" } ], "interactionCoverage": "label", "related": [ "eptifibatide" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "bnp", "name": "BNP", "aliases": [ "B-type Natriuretic Peptide", "Brain Natriuretic Peptide", "NT-proBNP" ], "tier": "mid", "category": "cardiovascular", "subcategory": "endogenous natriuretic peptide", "class": "A 32-amino-acid cardiac hormone released from ventricular myocytes in response to volume overload and wall stress.", "tagline": "The hormone a stretched heart releases: a standard blood test for heart failure since 2000, and the discontinued drug nesiritide.", "oneLiner": "A 32-amino-acid cardiac hormone released by stretched ventricular muscle; BNP and NT-proBNP blood levels diagnose heart failure.", "sequence": "SPKMVQGSGCFGRKMDRISSSSGLGCKVLRRH", "molecularFormula": "C143H244N50O42S4", "molecularWeight": 3464.1, "halfLife": { "value": null, "unit": null, "range": "about 18 minutes for recombinant BNP (nesiritide)", "source": { "type": "pmid", "pmid": "15992106", "cite": "Hobbs RE, et al. \"Therapeutic potential of nesiritide (recombinant b-type natriuretic peptide) in the treatment of heart failure.\" Expert Opin Investig Drugs, 1999;8(7):1063-72. PMID: 15992106." } }, "fdaStatus": "diagnostic", "approvalDetails": "Not a marketed drug: its recombinant form, nesiritide, is discontinued. BNP blood tests are FDA-authorized devices; Biosite's Triage BNP Test was granted de novo classification (DEN000010) on November 20, 2000.", "mechanism": "Binds natriuretic peptide receptor A (NPR-A), activating guanylyl cyclase and raising intracellular cGMP. Effects: vasodilation, natriuresis, diuresis, suppression of RAAS and sympathetic nervous system, anti-fibrotic and anti-hypertrophic cardiac effects.", "primaryUses": [ "Diagnosing heart failure in breathless patients (blood test)", "Selecting high-risk patients for prevention (research)" ], "typicalDose": { "range": null, "unit": null, "frequency": null, "route": "diagnostic blood test", "notes": "Not administered therapeutically in current practice. Nesiritide (recombinant BNP) was dosed at 2 mcg/kg bolus + 0.01 mcg/kg/min infusion but is rarely used." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Maisel AS, et al. \"Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure.\" N Engl J Med, 2002;347(3):161-7. PMID: 12124404.", "pmid": "12124404" }, { "type": "pubmed", "citation": "Januzzi JL Jr, et al. \"The N-terminal Pro-BNP investigation of dyspnea in the emergency department (PRIDE) study.\" Am J Cardiol, 2005;95(8):948-54. PMID: 15820160.", "pmid": "15820160" }, { "type": "pubmed", "citation": "Januzzi JL Jr, et al. \"N-Terminal Pro-B-Type Natriuretic Peptide in the Emergency Department: The ICON-RELOADED Study.\" J Am Coll Cardiol, 2018;71(11):1191-1200. PMID: 29544601.", "pmid": "29544601" }, { "type": "pubmed", "citation": "Huelsmann M, et al. \"PONTIAC (NT-proBNP selected prevention of cardiac events in a population of diabetic patients without a history of cardiac disease): a prospective randomized controlled trial.\" J Am Coll Cardiol, 2013;62(15):1365-72. PMID: 23810874.", "pmid": "23810874" }, { "type": "pubmed", "citation": "Hall C. \"Essential biochemistry and physiology of (NT-pro)BNP.\" Eur J Heart Fail, 2004;6(3):257-60. PMID: 14987573.", "pmid": "14987573" }, { "type": "pubmed", "citation": "Hobbs RE, et al. \"Therapeutic potential of nesiritide (recombinant b-type natriuretic peptide) in the treatment of heart failure.\" Expert Opin Investig Drugs, 1999;8(7):1063-72. PMID: 15992106.", "pmid": "15992106" }, { "type": "other", "citation": "US FDA, device records (openFDA 510(k) and de novo): DEN000010, TRIAGE B-TYPE NATRIURETIC PEPTIDE (BNP) TEST, Biosite Incorporated, November 20, 2000. Read September 30, 2026." } ], "interactionCoverage": "studied", "related": [ "nesiritide", "carperitide", "ularitide" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-20", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Measured in blood tests rather than given as a medicine; as a drug it exists only as nesiritide, whose WADA position is set out in that entry." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Measured in blood tests rather than given as a medicine; as a drug it exists only as nesiritide, whose WADA position is set out in that entry." } ], "moleculeClass": "peptide", "statusVerified": { "date": "2026-09-30", "source": "openFDA device records: DEN000010, Triage B-type Natriuretic Peptide Test, Biosite, November 20, 2000" } }, { "id": "botulinum-toxin", "name": "Botulinum Toxin", "aliases": [ "BoNT", "Botox", "onabotulinumtoxinA", "abobotulinumtoxinA", "incobotulinumtoxinA", "prabotulinumtoxinA", "rimabotulinumtoxinB", "Dysport", "Xeomin", "Jeuveau", "Myobloc" ], "tier": "mid", "category": "cosmetic", "subcategory": "neurotoxic protein (SNARE-cleaving protease)", "class": "A ~150 kDa two-chain protein neurotoxin produced by Clostridium botulinum, consisting of a 100 kDa heavy chain (binding and translocation) and a 50 kDa light chain (zinc-dependent protease). Seven serotypes (A–G) are known; clinical use centers on serotypes A and B.", "tagline": "A bacterial toxin that cleaves SNAP-25 to silence nerve endings: approved for migraine, bladder, spasticity and more, under a boxed warning.", "oneLiner": "A bacterial neurotoxin that cleaves SNAP-25 to block acetylcholine release, injected to relax muscles and glands and to prevent chronic migraine.", "sequence": "~1296-amino-acid precursor cleaved into 100 kDa heavy chain + 50 kDa light chain (sequences vary by serotype; the neurotoxin is a large protein rather than a short peptide)", "molecularFormula": null, "molecularWeight": 150000, "halfLife": { "value": null, "unit": null, "range": "not a blood half-life: it acts where it is injected, at nerve endings", "source": { "type": "qualitative", "note": "a description with no figure; no half-life measurement is cited for it" } }, "fdaStatus": "approved", "approvalDetails": "FDA-approved biologics, including Botox and Botox Cosmetic (onabotulinumtoxinA), BLA 103000, with a boxed warning for distant spread of toxin effect. Adults may receive no more than 400 Units of Botox in a 3-month interval.", "mechanism": "Heavy chain binds gangliosides (GT1b) and SV2 receptors on cholinergic presynaptic terminals, enabling receptor-mediated endocytosis. The endosome acidifies, triggering translocation of the 50 kDa light chain into the cytosol. The light chain is a zinc-dependent endopeptidase that cleaves SNARE complex proteins — SNAP-25 (serotypes A, E), VAMP/synaptobrevin (B, D, F, G), or syntaxin (C). Without intact SNARE proteins, acetylcholine-loaded synaptic vesicles cannot fuse with the presynaptic membrane, blocking neurotransmitter release and causing flaccid paralysis of the target muscle until nerve-terminal sprouting restores function.", "primaryUses": [ "Chronic migraine prevention", "Overactive and neurogenic bladder", "Spasticity and cervical dystonia", "Severe underarm sweating", "Blepharospasm and strabismus", "Cosmetic lines (Botox Cosmetic)" ], "typicalDose": { "range": "1–400", "unit": "units (product-specific)", "frequency": "every 3–6 months", "route": "intramuscular or intradermal injection", "notes": "Units are NOT interchangeable between products. Glabellar cosmetic dose is typically 20 units onabotulinumtoxinA; cervical dystonia 150–300 units; chronic migraine 155–195 units across 31–39 injection sites." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "BOTOX (onabotulinumtoxinA) for injection Prescribing Information, sections boxed warning, 1 and 2 (DailyMed version 62, effective November 18, 2023; read September 30, 2026)." }, { "type": "pubmed", "citation": "Lindsay C, et al. \"Can the early use of botulinum toxin in post stroke spasticity reduce contracture development? A randomised controlled trial.\" Clin Rehabil, 2021;35(3):399-409. PMID: 33040610.", "pmid": "33040610" }, { "type": "pubmed", "citation": "Fabi S, et al. \"Improvement of platysma prominence with onabotulinumtoxinA: Safety and efficacy results from a randomized, double-blinded, placebo-controlled phase 3 trial.\" J Am Acad Dermatol, 2025;92(2):285-291. PMID: 39442886.", "pmid": "39442886" }, { "type": "pubmed", "citation": "Kim SR, et al. \"Effect of Botulinum Toxin on Masticatory Muscle Pain in Patients with Temporomandibular Disorders: A Randomized, Double-Blind, Placebo-Controlled Pilot Study.\" Toxins (Basel), 2023;15(10). PMID: 37888628.", "pmid": "37888628" }, { "type": "pubmed", "citation": "Dressler D, et al. \"Botulinum toxin: mechanisms of action.\" Eur Neurol, 2005;53(1):3-9. PMID: 15650306.", "pmid": "15650306" }, { "type": "pubmed", "citation": "Burstein R, et al. \"Mechanism of Action of OnabotulinumtoxinA in Chronic Migraine: A Narrative Review.\" Headache, 2020;60(7):1259-1272. PMID: 32602955.", "pmid": "32602955" }, { "type": "pubmed", "citation": "Jankovic J. \"Botulinum toxin in clinical practice.\" J Neurol Neurosurg Psychiatry, 2004;75(7):951-7. PMID: 15201348.", "pmid": "15201348" }, { "type": "other", "citation": "US FDA, Drugs@FDA (openFDA): BOTOX and BOTOX COSMETIC (onabotulinumtoxinA), BLA 103000, Allergan, prescription. Read September 30, 2026." } ], "interactionCoverage": "partial", "related": [ "hyaluronic-acid", "argireline", "snap-8" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-20", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "protein", "moleculeClassBasis": "protein" }, { "id": "bpc-157", "name": "BPC-157", "aliases": [ "Body Protective Compound 157", "PL 14736", "Pentadecapeptide BPC 157" ], "tier": "full", "category": "healing", "subcategory": "gastric pentadecapeptide", "class": "Synthetic pentadecapeptide derived from a protective sequence in human gastric juice.", "tagline": "A synthetic pentadecapeptide from gastric protein, widely studied in animal models for tendon, ligament, and gastrointestinal healing.", "oneLiner": "A stable 15-amino-acid fragment of Body Protective Compound isolated from human gastric juice, studied in animal models for tissue repair, angiogenesis, and gut-brain axis effects.", "sequence": "GEPPPGKPADDAGLV", "molecularFormula": "C62H98N16O22", "molecularWeight": 1419.55, "halfLife": { "value": null, "unit": null, "range": "short systemic half-life (minutes) but prolonged tissue effect", "notes": "Plasma half-life is brief; biological effects persist well beyond plasma clearance, consistent with receptor-mediated and trophic mechanisms." }, "fdaStatus": "research-only", "approvalDetails": "Not approved by any regulatory body for any indication. Sold in compounded and research-chemical channels only.", "mechanism": "BPC-157 promotes angiogenesis via upregulation of VEGFR2 expression and activation of the Egr-1/NAB2 pathway, modulates nitric oxide signaling, and interacts with the dopaminergic and serotonergic systems in animal models. Effects are observed on tendon, ligament, muscle, bone, gastrointestinal tissue, and the blood-brain barrier. Despite extensive preclinical literature, no peer-reviewed human efficacy trials have been published as of 2026.", "primaryUses": [ "Tendon and ligament injury (animal models)", "Gastrointestinal ulceration (animal models)", "Inflammatory bowel disease (preclinical)", "Muscle and bone healing (preclinical)" ], "typicalDose": { "range": "250–500", "unit": "mcg", "frequency": "once or twice daily", "route": "subcutaneous (community use); oral forms also common despite unclear bioavailability", "notes": "No human dosing has been established through clinical trials. Community-reported dosing ranges widely." }, "evidenceLevel": "low", "sources": [ { "type": "review", "citation": "Sever AZ, et al. \"Stable gastric pentadecapeptide BPC 157 in the therapy of the rats with bile duct ligation.\" Eur J Pharmacol, 2019;847:130-142. PMID: 30690000.", "pmid": "30690000" }, { "type": "review", "citation": "Chang CH, et al. \"The promoting effect of pentadecapeptide BPC 157 on tendon healing involves tendon outgrowth, cell survival, and cell migration.\" J Appl Physiol, 2011. PMID: 21030672.", "pmid": "21030672" }, { "type": "pubmed", "citation": "Seiwerth S, et al. \"BPC 157 and standard angiogenic growth factors.\" Life Sci, 2018. PMID: 29998800.", "pmid": "29998800" }, { "type": "pubmed", "citation": "Lee E, et al. \"Safety of Intravenous Infusion of BPC157 in Humans: A Pilot Study.\" Altern Ther Health Med, 2025;31(5):20-24. PMID: 40131143.", "pmid": "40131143" }, { "type": "pubmed", "citation": "Vasireddi N, et al. \"Emerging Use of BPC-157 in Orthopaedic Sports Medicine: A Systematic Review.\" HSS J, 2025;21(4):485-495. PMID: 40756949.", "pmid": "40756949" }, { "type": "pubmed", "citation": "Chang CH, et al. \"Pentadecapeptide BPC 157 enhances the growth hormone receptor expression in tendon fibroblasts.\" Molecules, 2014;19(11):19066-77. PMID: 25415472.", "pmid": "25415472" }, { "type": "pubmed", "citation": "Seiwerth S, et al. \"BPC 157 and blood vessels.\" Curr Pharm Des, 2014;20(7):1121-5. PMID: 23782145.", "pmid": "23782145" }, { "type": "pubmed", "citation": "Tudor M, et al. \"Traumatic brain injury in mice and pentadecapeptide BPC 157 effect.\" Regul Pept, 2010;160(1-3):26-32. PMID: 19931318.", "pmid": "19931318" }, { "type": "pubmed", "citation": "Novinscak T, et al. \"Gastric pentadecapeptide BPC 157 as an effective therapy for muscle crush injury in the rat.\" Surg Today, 2008;38(8):716-25. PMID: 18668315.", "pmid": "18668315" }, { "type": "pubmed", "citation": "Xue XC, et al. \"Protective effects of pentadecapeptide BPC 157 on gastric ulcer in rats.\" World J Gastroenterol, 2004;10(7):1032-6. PMID: 15052688.", "pmid": "15052688" }, { "type": "pubmed", "citation": "Sikirić P, et al. \"Pentadecapeptide BPC 157 interactions with adrenergic and dopaminergic systems in mucosal protection in stress.\" Dig Dis Sci, 1997;42(3):661-71. PMID: 9073154.", "pmid": "9073154" }, { "type": "pubmed", "citation": "Hsieh MJ, et al. \"Therapeutic potential of pro-angiogenic BPC157 is associated with VEGFR2 activation and up-regulation.\" J Mol Med (Berl), 2017;95(3):323-333. PMID: 27847966.", "pmid": "27847966" } ], "interactionCoverage": "partial", "related": [ "tb-500", "ghk-cu", "kpv" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-01-15", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S0", "named": true, "wording": "BPC-157", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "It is the first substance S0 names, on page 4 of both Lists." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S0", "named": true, "wording": "BPC-157", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "It is the first substance S0 names, on page 4 of both Lists." } ], "moleculeClass": "peptide" }, { "id": "bradykinin", "name": "Bradykinin", "aliases": [ "BK", "Kallidin", "Kinin-9" ], "tier": "mid", "category": "cardiovascular", "subcategory": "Endogenous vasoactive peptide", "class": "Bradykinin is the endogenous vasodilator and inflammatory mediator whose pathway is directly modulated by ACE inhibitors — one of the world's most prescribed drug classes.", "tagline": "The peptide behind wheals, leaky vessels and asthma narrowing; never a treatment, but its B2 blocker icatibant treats angioedema attacks.", "oneLiner": "A nine-amino-acid kinin cut from kininogen by kallikreins that widens and loosens blood vessels and drives inflammation through B2 receptors.", "sequence": "RPPGFSPFR", "molecularFormula": "C50H73N15O11", "molecularWeight": 1060.22, "halfLife": { "value": null, "unit": null, "range": "not reported in the sources read", "source": { "type": "none", "note": "searched on September 30, 2026; no half-life reported in the sources read" } }, "fdaStatus": "research-only", "approvalDetails": "Not a medicine anywhere; no application appears in Drugs@FDA. Its B2 receptor blocker icatibant is approved as Firazyr for acute attacks of hereditary angioedema in adults.", "mechanism": "Generated by plasma kallikrein from high-molecular-weight kininogen. Binds B2 receptors (constitutive, Gq-coupled) causing vasodilation via endothelial NO and prostacyclin release, increased vascular permeability, and nociceptor activation. B1 receptors (inducible, upregulated in inflammation) mediate sustained inflammatory pain. Degraded primarily by ACE.", "primaryUses": [ "Research challenge agent (skin and airways)" ], "typicalDose": { "range": "N/A", "unit": "N/A", "frequency": "N/A", "route": "endogenous", "notes": "Not used as a drug. Clinical relevance is through modulation of its pathway." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Polosa R, et al. \"Skin responses to bradykinin, kallidin, and [desArg9]-bradykinin in nonatopic and atopic volunteers.\" J Allergy Clin Immunol, 1993;92(5):683-9. PMID: 8227859.", "pmid": "8227859" }, { "type": "pubmed", "citation": "Polosa R, et al. \"Comparative airway response to inhaled bradykinin, kallidin, and [des-Arg9]bradykinin in normal and asthmatic subjects.\" Am Rev Respir Dis, 1990;142(6 Pt 1):1367-71. PMID: 2174657.", "pmid": "2174657" }, { "type": "pubmed", "citation": "Gamboa JL, et al. \"Bradykinin B(2) receptor blockade and intradialytic hypotension.\" BMC Nephrol, 2023;24(1):134. PMID: 37170244.", "pmid": "37170244" }, { "type": "pubmed", "citation": "Marceau F, et al. \"Bradykinin receptor ligands: therapeutic perspectives.\" Nat Rev Drug Discov, 2004;3(10):845-52. PMID: 15459675.", "pmid": "15459675" }, { "type": "pubmed", "citation": "Garvin MR, et al. \"A mechanistic model and therapeutic interventions for COVID-19 involving a RAS-mediated bradykinin storm.\" Elife, 2020;9. PMID: 32633718.", "pmid": "32633718" }, { "type": "fda-pi", "citation": "FIRAZYR (icatibant) injection Prescribing Information, sections 1 (DailyMed version 19, effective July 7, 2025; read September 30, 2026)." }, { "type": "other", "citation": "US FDA, Drugs@FDA (openFDA): no application for bradykinin. Read September 30, 2026." } ], "interactionCoverage": "unreviewed", "related": [ "angiotensin-ii", "icatibant", "anp", "bnp", "vasopressin" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-21", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "brn2", "name": "BRN2 (POU3F2) Research Peptide", "aliases": [ "POU3F2-derived peptide", "N-Oct3 fragment" ], "tier": "stub", "category": "cognitive", "subcategory": "Transcription-factor-derived research peptide", "class": "Short peptide fragment derived from the POU3F2 (BRN2) neural transcription factor, investigated in a small body of preclinical literature as a modulator of neuronal differentiation and lineage specification.", "tagline": "A research-only peptide derived from the POU3F2 (BRN2) neural transcription factor; mechanistic and phenotypic evidence is limited almost entirely to in vitro and lineage-specification studies. No human therapeutic development, no clinical trials, no established dosing, and no commercial availability through regulated channels.", "oneLiner": "A short peptide fragment corresponding to a sequence within the POU-domain transcription factor BRN2 (encoded by POU3F2, also called N-Oct3). BRN2 is required for specification and differentiation of cortical upper-layer neurons and of melanocyte progenitors. The peptide has appeared sporadically in preclinical transcription-factor mimetic literature and in nootropic-adjacent grey-market catalogs. There is no coherent clinical development program, no human pharmacokinetic or safety data, and no substantiated therapeutic claim.", "sequence": "Not standardized (various BRN2-derived fragments reported in different preclinical reports)", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": null, "range": "Not characterized", "notes": "No pharmacokinetic data." }, "fdaStatus": "research-only", "approvalDetails": "Not FDA-approved. Not in any registered clinical trial. No therapeutic sponsor. Circulates in grey-market nootropic listings with unverified provenance and purity; any human use would be entirely unregulated and unsupported.", "mechanism": "BRN2 is a class III POU-domain transcription factor required for the specification of upper-layer cortical neurons and of the melanocyte lineage. Short peptides derived from the BRN2 sequence have been studied as tools for probing transcription factor function or as putative cell-penetrating fragments. No coherent cellular or in vivo mechanism of action as a therapeutic peptide has been established.", "primaryUses": [ "Transcription-factor research (in vitro)", "Neuronal differentiation studies (in vitro)" ], "typicalDose": { "range": "Not established", "unit": null, "frequency": null, "route": null, "notes": "⚠ No human dosing has ever been established. Any human use would be entirely experimental and unsupported by preclinical safety or efficacy data." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "McEvilly RJ, et al. \"Transcriptional regulation of cortical neuron migration by POU domain factors.\" Science, 2002;295:1528-1532 (BRN2 developmental biology). PMID: 11859196.", "pmid": "11859196" }, { "type": "pubmed", "citation": "Cook AL, et al. \"POU domain transcription factors: BRN2 as a regulator of melanocytic growth and tumourigenesis.\" Pigment Cell Melanoma Res, 2008;21(6):611-26. PMID: 18983536.", "pmid": "18983536" } ], "interactionCoverage": "unreviewed", "related": [ "npas3-peptide", "p21" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "bronchogen", "name": "Bronchogen", "aliases": [ "Ala-Glu-Asp-Leu", "AEDL" ], "tier": "stub", "category": "longevity", "subcategory": "Khavinson short-chain bioregulator (bronchial epithelium)", "class": "A synthetic short tetrapeptide derived from bronchial tissue extract, developed by the Khavinson group as a \"bronchial bioregulator\".", "tagline": "A Khavinson tetrapeptide from bronchial tissue — proposed to support respiratory epithelium function in chronic obstructive airway disease; evidence is preliminary and Russian-language.", "oneLiner": "One of the Khavinson short-chain bioregulators (Ala-Glu-Asp-Leu), derived from bronchial mucosal extract and proposed to support epithelial regeneration and ciliary function in aging lung tissue and in chronic obstructive pulmonary disease models.", "sequence": "Ala-Glu-Asp-Leu", "molecularFormula": "C19H32N4O8", "molecularWeight": 444.48, "halfLife": { "value": null, "unit": null, "range": "undetermined", "notes": "Pharmacokinetics not characterized in Western-standard studies." }, "fdaStatus": "research-only", "approvalDetails": "Not FDA-approved. Marketed in Russia as a bioregulator supplement.", "mechanism": "Proposed to act on bronchial epithelial cells via promoter binding to upregulate expression of genes supporting ciliary function and epithelial repair. Khavinson-group animal studies report reduced inflammation and improved mucociliary clearance in experimental COPD models.", "primaryUses": [ "Investigational adjunct in chronic obstructive pulmonary disease (Russian literature)", "Research into respiratory aging" ], "typicalDose": { "range": "not established", "unit": null, "frequency": "not established", "route": "oral (capsule) or intranasal", "notes": "Russian supplement protocols typically use 10 mg oral capsules once daily for 10–20 days." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Khavinson VK, Kuznik BI, Ryzhak GA. \"Peptide bioregulators: a new class of geroprotectors. Message 1. Results of experimental studies.\" Adv Gerontol, 2012;25:696-708. PMID: 23734519.", "pmid": "23734519" }, { "type": "review", "citation": "Khavinson VK, Malinin VV. \"Gerontological aspects of genome peptide regulation.\" Karger AG, Basel, 2005." } ], "interactionCoverage": "none-found", "related": [ "chonluten", "cortagen", "epithalon" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "buserelin", "name": "Buserelin", "aliases": [ "Suprecur", "Suprefact", "Bigonist", "Profact" ], "tier": "mid", "category": "sexual-health", "subcategory": "GnRH agonist", "class": "Synthetic GnRH agonist with D-Ser(tBu) at position 6 and ethylamide at position 10. Marketed outside the United States; never FDA-approved.", "tagline": "A GnRH agonist widely used in Canada, the UK, Germany, and other markets (Suprecur, Suprefact) for prostate cancer, endometriosis, and IVF downregulation — but never FDA-approved in the United States.", "oneLiner": "A synthetic nonapeptide GnRH agonist structurally related to leuprolide, marketed internationally as Suprefact (SC injection and nasal spray) and Suprecur (nasal spray and SC depot) by Sanofi and Cheplapharm for prostate cancer, endometriosis, and IVF controlled-ovarian-stimulation downregulation. Buserelin has never been FDA-approved in the United States; its absence from US practice reflects commercial rather than safety factors — leuprolide and goserelin secured the US market first.", "sequence": "pGlu-His-Trp-Ser-Tyr-D-Ser(tBu)-Leu-Arg-Pro-NHEt", "molecularFormula": "C60H86N16O13", "molecularWeight": 1239.4, "halfLife": { "value": null, "unit": null, "range": "not reported in the sources read", "source": { "type": "none", "note": "searched PubMed on October 1, 2026; no human half-life figure in the sources read" } }, "fdaStatus": "not-approved-us", "approvalDetails": "Not approved in the United States; no application appears in Drugs@FDA (read October 1, 2026). Licensed in Europe as Suprefact and Suprecur since the 1980s, in nasal and injectable forms.", "mechanism": "Pituitary GnRH-receptor agonism — chronic exposure desensitizes the receptor and suppresses LH, FSH, testosterone, and estradiol after an initial flare. Mechanism identical to leuprolide, triptorelin, and goserelin.", "primaryUses": [ "Advanced prostate cancer (ex-US)", "Endometriosis (ex-US)", "Uterine fibroids (ex-US)", "IVF downregulation in long-protocol controlled ovarian stimulation (ex-US)" ], "typicalDose": { "range": null, "unit": null, "frequency": null, "route": "intranasal or subcutaneous", "notes": "Not approved in the United States, so no US label dose exists. European use has been intranasal and subcutaneous, and a published paper addresses the dosage question directly." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Tapanainen J, et al. \"Subcutaneous goserelin versus intranasal buserelin for pituitary down-regulation in patients undergoing IVF: a randomized comparative study.\" Hum Reprod, 1993;8(12):2052-5. PMID: 8150902.", "pmid": "8150902" }, { "type": "pubmed", "citation": "Oyesanya OA, et al. \"Pituitary down-regulation prior to in-vitro fertilization and embryo transfer: a comparison between a single dose of Zoladex depot and multiple daily doses of Suprefact.\" Hum Reprod, 1995;10(5):1042-4. PMID: 7657737.", "pmid": "7657737" }, { "type": "pubmed", "citation": "Schindler AE, et al. \"[Treatment of endometriosis with the GnRH agonist buserelin (Suprecur): a multicenter study].\" Geburtshilfe Frauenheilkd, 1994;54(10):569-73. PMID: 8001754.", "pmid": "8001754" }, { "type": "pubmed", "citation": "Okuda K, et al. \"Effect of LHRH agonist (buserelin) on pulsatile secretion of LHRH and LH.\" Nihon Sanka Fujinka Gakkai Zasshi, 1988;40(12):1889-93. PMID: 3145318.", "pmid": "3145318" }, { "type": "pubmed", "citation": "Yu N. \"Dosage of buserelin.\" J Reprod Med, 2000;45(11):964-5. PMID: 11127117.", "pmid": "11127117" }, { "type": "other", "citation": "Suprefact (buserelin acetate) Product Monograph. Sanofi-Aventis Canada." }, { "type": "other", "citation": "Suprefact Summary of Product Characteristics. Electronic Medicines Compendium (eMC), United Kingdom." }, { "type": "review", "citation": "Del Moral-Sanchez JM, et al. \"Worldwide Availability of GnRH Agonists in Oncology and Reproductive Medicine.\" Pharmaceutics." } ], "interactionCoverage": "none-found", "related": [ "leuprolide", "triptorelin", "goserelin", "gonadorelin" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": "Canada, UK, Germany, Australia, much of the EU", "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.2.1", "named": true, "wording": "buserelin", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "malesOnly": true, "monitoring": "GnRH analogues in female athletes under 18, in and out of competition" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.2.1", "named": true, "wording": "buserelin", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "malesOnly": true, "monitoring": "GnRH analogues in female athletes under 18, in and out of competition" } ], "moleculeClass": "peptide" }, { "id": "cagrilintide", "name": "Cagrilintide", "aliases": [ "AM833", "NNC0174-0833" ], "tier": "mid", "category": "metabolic", "subcategory": "amylin analog", "class": "Long-acting synthetic analog of the pancreatic β-cell hormone amylin.", "tagline": "Novo Nordisk's weekly, lipidated amylin analogue: up to 10.8% weight loss alone in a 26-week phase 2 trial, and with semaglutide as CagriSema 20.4% over 68 weeks in REDEFINE 1. Investigational; not approved anywhere.", "oneLiner": "A 37-amino-acid cyclic peptide analog of amylin with backbone modifications for prolonged half-life, engineered for weekly subcutaneous dosing in obesity combination regimens.", "sequence": null, "molecularFormula": "C194H312N54O59S2", "molecularWeight": 4409, "halfLife": { "value": null, "unit": null, "range": "Long-acting; supports once-weekly dosing", "notes": "No half-life value appears in the abstracts read; the earlier '~7 days' had no source.", "source": { "type": "qualitative", "note": "a description with no figure; no half-life measurement is cited for it" } }, "fdaStatus": "clinical-trials", "approvalDetails": "Investigational. Phase 2 alone (PMID 34798060) and phase 3 with semaglutide as CagriSema (REDEFINE 1 and 2, 2025). Drugs@FDA holds no application and EMA's register has no entry (both read September 30, 2026).", "mechanism": "Dual agonism at amylin and calcitonin receptors. Amylin pathway activation suppresses food intake via hindbrain circuitry distinct from (and complementary to) GLP-1 appetite signaling, slows gastric emptying, and reduces glucagon secretion. Combination with semaglutide in CagriSema produced 22.7% weight loss at 68 weeks in REDEFINE 1 — numerically greater than semaglutide alone.", "primaryUses": [ "Obesity — Phase 3 (as CagriSema combination)", "Type 2 diabetes — Phase 3" ], "typicalDose": { "range": "0.3–2.4", "unit": "mg", "frequency": "weekly", "route": "subcutaneous", "notes": "In CagriSema trials: titrated over 16 weeks to 2.4 mg weekly. Not available as monotherapy." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "Lau DCW, et al. \"Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial.\" Lancet, 2021;398(10317):2160-2172. PMID: 34798060.", "pmid": "34798060" }, { "type": "pubmed", "citation": "Garvey WT, et al. \"Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity.\" N Engl J Med, 2025;393(7):635-647. PMID: 40544433.", "pmid": "40544433" }, { "type": "pubmed", "citation": "Davies MJ, et al. \"Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes.\" N Engl J Med, 2025;393(7):648-659. PMID: 40544432.", "pmid": "40544432" }, { "type": "pubmed", "citation": "Enebo LB, et al. \"Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2·4 mg for weight management: a randomised, controlled, phase 1b trial.\" Lancet, 2021;397(10286):1736-1748. PMID: 33894838.", "pmid": "33894838" }, { "type": "pubmed", "citation": "Nielsen MJF, et al. \"Renal or Hepatic Impairment Does Not Affect Pharmacokinetics, Safety, or Tolerability of Subcutaneous Cagrilintide.\" Clin Pharmacokinet, 2026;65(7):1087-1099. PMID: 42228334.", "pmid": "42228334" }, { "type": "pubmed", "citation": "Kruse T, et al. \"Development of Cagrilintide, a Long-Acting Amylin Analogue.\" J Med Chem, 2021;64(15):11183-11194. PMID: 34288673.", "pmid": "34288673" }, { "type": "pubmed", "citation": "Carvas AO, et al. \"Cagrilintide lowers bodyweight through brain amylin receptors 1 and 3.\" EBioMedicine, 2025;118:105836. PMID: 40609154.", "pmid": "40609154" }, { "type": "fda", "citation": "FDA. Drugs@FDA (openFDA): no application for cagrilintide. Read September 30, 2026." }, { "type": "other", "citation": "European Medicines Agency. Medicines register: no entry for cagrilintide. Read September 30, 2026." } ], "interactionCoverage": "studied", "related": [ "semaglutide", "tirzepatide" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." } ], "moleculeClass": "peptide" }, { "id": "cagrisema", "name": "CagriSema", "aliases": [ "cagrilintide/semaglutide 2.4/2.4", "NN9838" ], "tier": "full", "category": "pipeline", "subcategory": "GLP-1 + amylin fixed-dose combination", "class": "A fixed-dose combination of cagrilintide (long-acting amylin analog) 2.4 mg and semaglutide 2.4 mg in a single once-weekly injection.", "tagline": "Novo Nordisk's next-generation obesity injection — NDA filed December 2025, FDA review expected 2026. If approved, it would be the first GLP-1 + amylin fixed-dose combination and a direct competitive response to tirzepatide.", "oneLiner": "A once-weekly fixed-dose subcutaneous combination of semaglutide 2.4 mg (GLP-1 receptor agonist, the active ingredient in Wegovy) with cagrilintide 2.4 mg (a long-acting amylin analog), submitted by Novo Nordisk to the FDA as a New Drug Application on December 18, 2025 for chronic weight management in adults with obesity or overweight with at least one weight-related comorbidity.", "sequence": null, "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": "days", "range": "semaglutide ~165 hours; cagrilintide ~170 hours", "notes": "Both components engineered for once-weekly dosing; combined half-lives support the weekly regimen." }, "fdaStatus": "in-development", "approvalDetails": "NDA submitted to FDA December 18, 2025 based on the REDEFINE 1 Phase 3 trial. Novo Nordisk developer. FDA review expected 2026. In REDEFINE 1 (68 weeks, 3,417 adults with obesity or overweight), CagriSema produced approximately 23% mean body weight reduction under the trial-product estimand and approximately 20.4% under the treatment-policy estimand, versus ~3% for placebo.", "mechanism": "Dual-mechanism appetite suppression and weight loss. Semaglutide activates the GLP-1 receptor, slowing gastric emptying, suppressing glucagon, and acting centrally on hypothalamic appetite circuits. Cagrilintide activates amylin and calcitonin receptors (amylin is co-secreted with insulin from pancreatic beta cells), which independently reduce food intake, enhance satiety, and appear to restore leptin sensitivity. Combining the two mechanisms produces additive-to-synergistic weight loss in clinical trials.", "primaryUses": [ "Chronic weight management in adults with obesity (BMI ≥30) or overweight (BMI ≥27) with at least one comorbidity (investigational)", "Not yet approved for any use" ], "typicalDose": { "range": "2.4 / 2.4", "unit": "mg", "frequency": "once weekly", "route": "subcutaneous", "notes": "Investigational regimen from REDEFINE 1. Dose titration protocol mirrors semaglutide up-titration." }, "evidenceLevel": "high", "sources": [ { "type": "news-release", "citation": "Novo Nordisk. \"Novo Nordisk Files for FDA Approval of CagriSema, the First Once-Weekly Combination of GLP-1 and Amylin Analogues for Weight Management.\" December 18, 2025." }, { "type": "clinical-trial", "citation": "REDEFINE 1 Phase 3 trial (68 weeks, 3,417 participants). Novo Nordisk. 2025. Results released December 2024 / 2025." }, { "type": "pubmed", "citation": "Garvey WT, et al. \"Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity.\" N Engl J Med, 2025;393(7):635-647. PMID: 40544433.", "pmid": "40544433" }, { "type": "pubmed", "citation": "Davies MJ, et al. \"Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes.\" N Engl J Med, 2025;393(7):648-659. PMID: 40544432.", "pmid": "40544432" }, { "type": "pubmed", "citation": "Verma S, et al. \"CagriSema Reduces Blood Pressure in Adults With Overweight or Obesity: REDEFINE 1.\" Hypertension, 2026;83(2):e26055. PMID: 41328546.", "pmid": "41328546" }, { "type": "pubmed", "citation": "Frias JP, et al. \"Efficacy and safety of co-administered once-weekly cagrilintide 2·4 mg with once-weekly semaglutide 2·4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial.\" Lancet, 2023;402(10403):720-730. PMID: 37364590.", "pmid": "37364590" }, { "type": "pubmed", "citation": "Lau DCW, et al. \"Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial.\" Lancet, 2021;398(10317):2160-2172. PMID: 34798060.", "pmid": "34798060" }, { "type": "pubmed", "citation": "Enebo LB, et al. \"Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2·4 mg for weight management: a randomised, controlled, phase 1b trial.\" Lancet, 2021;397(10286):1736-1748. PMID: 33894838.", "pmid": "33894838" }, { "type": "pubmed", "citation": "Wilding JPH, et al. \"Once-Weekly Semaglutide in Adults with Overweight or Obesity.\" N Engl J Med, 2021;384(11):989-1002. PMID: 33567185.", "pmid": "33567185" } ], "interactionCoverage": "partial", "related": [ "semaglutide", "cagrilintide", "tirzepatide", "petrelintide" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." } ], "moleculeClass": "blend", "moleculeClassBasis": "fixed-dose combination" }, { "id": "calcitonin", "name": "Calcitonin", "aliases": [ "Miacalcin", "Fortical", "Salmon Calcitonin", "Calcitonin-Salmon" ], "tier": "mid", "category": "healing", "subcategory": "endogenous bone-regulating hormone", "class": "A 32-amino-acid peptide hormone produced by thyroid C-cells that inhibits osteoclast activity and reduces bone resorption.", "tagline": "The hormone that switches off bone-dissolving cells: one 1,255-woman fracture trial, and a later option now that stronger drugs exist.", "oneLiner": "A 32-amino-acid hormone, given as the more potent salmon sequence, that slows bone breakdown and lowers blood calcium.", "sequence": "CSNLSTCVLGKLSQELHKLQTYPRTNTGSGTP-NH2 (salmon; Cys1-Cys7 disulfide)", "molecularFormula": "C145H240N44O48S2", "molecularWeight": 3432.0, "halfLife": { "value": 58, "unit": "minutes", "range": "about 58 minutes intramuscular, 59 to 64 minutes subcutaneous", "source": { "type": "label", "ref": "Miacalcin injection prescribing information, section 12.3 (DailyMed version 5, effective September 15, 2024; read September 30, 2026)" } }, "fdaStatus": "approved", "approvalDetails": "FDA-approved as Miacalcin (calcitonin salmon) injection and as nasal spray products. Pooled long-term trials showed more cancers on calcitonin, and several regulators have since restricted long-term use for osteoporosis.", "mechanism": "Binds the calcitonin receptor (CTR, a class B GPCR) on osteoclasts, activating Gs → cAMP and causing rapid cytoskeletal disruption, loss of ruffled border, and cessation of bone resorption. Also has analgesic effects in acute vertebral fractures, possibly via central serotonergic and endorphinergic pathways. The CTR in complex with RAMPs forms amylin receptors (AMY1–3), relevant to metabolic pharmacology.", "primaryUses": [ "Postmenopausal osteoporosis", "Hypercalcaemia", "Paget's disease of bone" ], "typicalDose": { "range": "200", "unit": "IU", "frequency": "once daily (nasal) or 100 IU SC/IM every other day", "route": "intranasal or subcutaneous", "notes": "Nasal spray is most common. Alternate nostrils daily. Long-term use limited by tachyphylaxis and cancer signal." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Miacalcin (calcitonin salmon) injection Prescribing Information. (DailyMed version 5, effective September 15, 2024; read September 30, 2026)." }, { "type": "pubmed", "citation": "Chesnut CH 3rd, et al. \"A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study. PROOF Study Group.\" Am J Med, 2000;109(4):267-76. PMID: 10996576.", "pmid": "10996576" }, { "type": "pubmed", "citation": "MacIntyre I, et al. \"Calcitonin for prevention of postmenopausal bone loss.\" Lancet, 1988;1(8591):900-2. PMID: 2895829.", "pmid": "2895829" }, { "type": "pubmed", "citation": "Henriksen K, et al. \"Oral salmon calcitonin--pharmacology in osteoporosis.\" Expert Opin Biol Ther, 2010;10(11):1617-29. PMID: 20932224.", "pmid": "20932224" }, { "type": "other", "citation": "US FDA, Drugs@FDA (openFDA): calcitonin salmon products, prescription. Read September 30, 2026." } ], "interactionCoverage": "label", "related": [ "teriparatide", "amylin" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-20", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "capromorelin", "name": "Capromorelin", "aliases": [ "Entyce", "Elura", "CP-424,391" ], "tier": "stub", "category": "growth-hormone", "subcategory": "orally active ghrelin receptor agonist (veterinary-approved)", "class": "A small-molecule orally active ghrelin receptor (GHS-R1a) agonist, FDA-approved for veterinary use (dogs and cats) as an appetite stimulant.", "tagline": "⚠ Veterinary use only — not approved for humans. Elanco's oral ghrelin agonist (Entyce for dogs 2016, Elura for cats 2020) — FDA-approved only for veterinary appetite stimulation. Included for completeness because it is a genuine approved ghrelin receptor agonist with significant online search volume.", "oneLiner": "⚠ Veterinary use only — not approved for humans. A small-molecule orally active ghrelin receptor (GHS-R1a) agonist originally developed by Pfizer for human GH deficiency (Phase 2 completed, discontinued for strategic reasons around 2004) and later repurposed for veterinary appetite stimulation. FDA Center for Veterinary Medicine approved capromorelin as Entyce for dogs in May 2016 (first and to date only FDA-approved appetite stimulant for dogs) and as Elura for the management of weight loss in cats with chronic kidney disease in August 2020. Marketed by Elanco. Included here for reference because it is one of the few GHS agonists with any regulatory approval and because it appears frequently in search queries adjacent to MK-677 — but it is not appropriate for human use.", "sequence": null, "molecularFormula": "C27H38N4O4", "molecularWeight": 482.6, "halfLife": { "value": 2, "unit": "hours", "range": "~1.5–3 hours (canine)", "notes": "Veterinary pharmacokinetics; human PK studied at Phase 2 scale but not the standard of reference." }, "fdaStatus": "veterinary", "approvalDetails": "FDA Center for Veterinary Medicine approved Entyce (capromorelin oral solution 30 mg/mL) for dogs in May 2016 for appetite stimulation. Elura (capromorelin oral solution 20 mg/mL) approved August 2020 for management of weight loss in cats with chronic kidney disease. Marketed by Elanco. Original Pfizer human GHD program discontinued mid-2000s.", "mechanism": "Full agonist at the ghrelin receptor (GHS-R1a) in hypothalamus, pituitary somatotrophs, and vagal afferents. Produces appetite stimulation via NPY/AgRP hypothalamic circuits, modest GH release, and prokinetic effects. In dogs and cats, onset of eating behavior is typically within 1–2 hours of dosing.", "primaryUses": [ "⚠ Canine appetite stimulation (Entyce — FDA-approved)", "⚠ Feline CKD-associated weight loss (Elura — FDA-approved)", "Not approved for human use" ], "typicalDose": { "range": null, "unit": null, "frequency": null, "route": null, "notes": "⚠ Veterinary dosing only (Entyce: 3 mg/kg PO once daily in dogs; Elura: 2 mg/kg PO once daily in cats). There is no human dose and capromorelin is not labeled, quality-controlled, or studied for human use in the current market." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Entyce (capromorelin oral solution) NADA 141-457. FDA Center for Veterinary Medicine." }, { "type": "fda-pi", "citation": "Elura (capromorelin oral solution) NADA 141-536. FDA Center for Veterinary Medicine." }, { "type": "pubmed", "citation": "Zollers B, et al. \"A prospective, randomized, masked, placebo-controlled clinical study of capromorelin in dogs with reduced appetite.\" J Vet Intern Med, 2016;30:1851-1857. PMID: 27859746.", "pmid": "27859746" } ], "interactionCoverage": "none-found", "related": [ "mk-677", "anamorelin", "ghrp-2", "ghrp-6" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.2.4", "named": true, "wording": "capromorelin", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.2.4", "named": true, "wording": "capromorelin", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "small-molecule", "moleculeClassBasis": "small-molecule", "statusVerified": { "date": "2026-09-30", "source": "FDA Center for Veterinary Medicine approvals of Entyce (2016) and Elura (2020) as recorded in the entry; never approved for human use" } }, { "id": "carbetocin", "name": "Carbetocin", "aliases": [ "Pabal", "Duratocin", "Lonactene", "Heat-Stable Carbetocin (HSC)" ], "tier": "full", "category": "sexual-health", "subcategory": "oxytocin analog", "class": "Synthetic long-acting oxytocin analog — a deamino, carba-1, O-methyltyrosine-2 oxytocin derivative with 4–10× longer half-life than native oxytocin, used to prevent postpartum hemorrhage.", "tagline": "Ferring's Pabal / Duratocin — a long-acting oxytocin analogue given once after birth to prevent postpartum haemorrhage. Heat-stable carbetocin matched oxytocin in WHO's 29,645-woman CHAMPION trial, and WHO's 2025 guideline recommends carbetocin for all births. Not FDA-approved.", "oneLiner": "A synthetic long-acting oxytocin analog (1-deamino-1-monocarba-2-O-methyltyrosine-oxytocin) developed by Ferring, with a plasma half-life of approximately 40 minutes — roughly 4–10× longer than native oxytocin — supporting single-dose use for postpartum hemorrhage prevention after cesarean delivery. Approved in Canada (Duratocin, 1997), the EU and UK (Pabal), and many other jurisdictions. A room-temperature-stable formulation (heat-stable carbetocin, HSC) was prequalified by the WHO in 2019 for use in low-resource settings without cold-chain infrastructure. The FDA declined to approve carbetocin in 2006 and Ferring has not re-filed.", "sequence": "(Deamino-Cys-carba)-Tyr(Me)-Ile-Gln-Asn-Cys-Pro-Leu-Gly-NH2 (cyclic, modified)", "molecularFormula": "C45H69N11O12S", "molecularWeight": 988.2, "halfLife": { "value": 41, "unit": "minutes", "range": "41 to 43 minutes after IV doses (healthy nonpregnant women)", "notes": "Distribution half-life 5.5 to 6.1 minutes; IM bioavailability about 80%; about 0.7% excreted unchanged in urine (pharmacokinetic study in 25 women, Lund University publication record)." }, "fdaStatus": "not-approved-us", "approvalDetails": "Not FDA-approved: Drugs@FDA holds no application (read September 30, 2026). UK: authorised as Pabal (Ferring) for prevention of postpartum haemorrhage due to uterine atony, 100 µg once after delivery, IV at caesarean and IV or IM after vaginal birth (SmPC on EMC, last updated August 6, 2025); Ferring also markets it as Duratocin and Lonactene. WHO: heat-stable carbetocin on the Model List of Essential Medicines since 2019; the 2025 WHO postpartum haemorrhage guideline recommends carbetocin for all births and heat-stable carbetocin where the oxytocin cold chain cannot be maintained. The Scottish Medicines Consortium did not recommend Pabal for NHS Scotland (December 2017).", "mechanism": "Selective OXTR agonism on uterine myometrium, producing sustained tonic and phasic uterine contractions that compress uterine blood vessels and reduce postpartum bleeding. Minimal vasopressin-receptor activity. Longer half-life than oxytocin enables single-dose use in place of a prolonged oxytocin infusion.", "primaryUses": [ "Prevention of postpartum hemorrhage (uterine atony) after elective cesarean delivery (ex-US)", "Prevention of postpartum hemorrhage after vaginal delivery (heat-stable carbetocin, WHO-prequalified, low-resource settings)" ], "typicalDose": { "range": "100", "unit": "µg", "frequency": "single dose after delivery", "route": "IV or IM", "notes": "UK label: IV only at caesarean (slowly, over 1 minute); IV or IM after vaginal birth; no repeat doses." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Ferring Pharmaceuticals. PABAL 100 micrograms/ml solution for injection, Summary of Product Characteristics, sections 4.1-4.2 (prevention of postpartum haemorrhage due to uterine atony; 100 µg once, IV at caesarean, IV or IM after vaginal delivery). EMC, last updated August 6, 2025; read September 30, 2026." }, { "type": "clinical-trial", "citation": "Pharmacokinetics of carbetocin, a long-acting oxytocin analogue, in nonpregnant women (25 healthy women; elimination half-life 41 and 42.7 minutes after 0.4 and 0.8 mg IV; IM bioavailability about 80%). Not PubMed-indexed; English summary read in Lund University's publication record, September 30, 2026." }, { "type": "pubmed", "citation": "Widmer M, et al. \"Heat-Stable Carbetocin versus Oxytocin to Prevent Hemorrhage after Vaginal Birth.\" N Engl J Med, 2018;379(8):743-752. PMID: 29949473.", "pmid": "29949473" }, { "type": "pubmed", "citation": "Vernekar SS, et al. \"Effect of heat stable carbetocin vs oxytocin for preventing postpartum haemorrhage on post delivery hemoglobin-a randomized controlled trial.\" J Matern Fetal Neonatal Med, 2022;35(25):8744-8751. PMID: 34763599.", "pmid": "34763599" }, { "type": "pubmed", "citation": "Jin XH, et al. \"Carbetocin vs oxytocin for prevention of postpartum hemorrhage after vaginal delivery: A meta-analysis.\" Medicine (Baltimore), 2019;98(47):e17911. PMID: 31764790.", "pmid": "31764790" }, { "type": "pubmed", "citation": "Kalafat E, et al. \"Efficacy of carbetocin in the prevention of postpartum hemorrhage: a systematic review and Bayesian meta-analysis of randomized trials.\" J Matern Fetal Neonatal Med, 2021;34(14):2303-2316. PMID: 31537134.", "pmid": "31537134" }, { "type": "pubmed", "citation": "McDonagh F, et al. \"Carbetocin vs. oxytocin at elective caesarean delivery: a double-blind, randomised, controlled, non-inferiority trial of low- and high-dose regimens.\" Anaesthesia, 2022;77(8):892-900. PMID: 35343585.", "pmid": "35343585" }, { "type": "pubmed", "citation": "Roof E, et al. \"Intranasal Carbetocin Reduces Hyperphagia, Anxiousness, and Distress in Prader-Willi Syndrome: CARE-PWS Phase 3 Trial.\" J Clin Endocrinol Metab, 2023;108(7):1696-1708. PMID: 36633570.", "pmid": "36633570" }, { "type": "pubmed", "citation": "Theunissen FJ, et al. \"Current research on carbetocin and implications for prevention of postpartum haemorrhage.\" Reprod Health, 2018;15(Suppl 1):94. PMID: 29945640.", "pmid": "29945640" }, { "type": "pubmed", "citation": "Sun P, et al. \"Pharmacokinetics and bioavailability of carbetocin after intravenous and intramuscular administration in cows and gilts.\" J Vet Pharmacol Ther, 2020;43(2):237-240. PMID: 31856330.", "pmid": "31856330" }, { "type": "guideline", "citation": "World Health Organization (2025). Consolidated guidelines for the prevention, diagnosis and treatment of postpartum haemorrhage: carbetocin 100 µg IM/IV recommended for all births; heat-stable carbetocin where the oxytocin cold chain cannot be maintained. Recommendations read in the PAHO/BVS BIGG-rec database, September 30, 2026." }, { "type": "other", "citation": "World Health Organization. Model List of Essential Medicines: carbetocin (heat stable), 100 µg/mL injection, core list, first added in 2019 (TRS 1021). Read at list.essentialmeds.org, September 30, 2026." }, { "type": "other", "citation": "Scottish Medicines Consortium. Carbetocin 100 micrograms/mL solution for injection (Pabal), SMC No 309/06: not recommended for use within NHS Scotland (advice of December 8, 2017, published January 15, 2018)." }, { "type": "fda", "citation": "FDA. Drugs@FDA (openFDA): no application for carbetocin. Read September 30, 2026." } ], "interactionCoverage": "none-found", "related": [ "oxytocin", "atosiban" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": "Canada, EU, UK", "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "cardiogen", "name": "Cardiogen", "aliases": [ "Ala-Glu-Asp-Arg", "AEDR" ], "tier": "stub", "category": "longevity", "subcategory": "Khavinson short-chain bioregulator (cardiac)", "class": "A synthetic short tetrapeptide derived from bovine heart tissue extract, developed by the Khavinson group as a \"cardiac bioregulator\".", "tagline": "A Khavinson-group tetrapeptide from heart-tissue extract — proposed to support cardiomyocyte function and cardiac tissue aging; evidence base is Russian-language and largely pre-clinical.", "oneLiner": "A short tetrapeptide (Ala-Glu-Asp-Arg) in the Khavinson bioregulator series, derived from bovine myocardial extract and proposed to support cardiomyocyte function and tissue homeostasis in the aging heart via tissue-specific gene-expression modulation.", "sequence": "Ala-Glu-Asp-Arg", "molecularFormula": "C17H30N8O8", "molecularWeight": 474.47, "halfLife": { "value": null, "unit": null, "range": "undetermined", "notes": "Pharmacokinetics not characterized in Western-standard studies." }, "fdaStatus": "research-only", "approvalDetails": "Not FDA-approved. Marketed as a bioregulator / supplement in Russia and some CIS countries.", "mechanism": "Proposed by the Khavinson group to function as a tissue-specific transcriptional regulator in cardiomyocytes — short peptide binding to promoter regions is hypothesized to upregulate expression of proteins supporting contractile function and resistance to ischemic stress in aged tissue. Mechanistic evidence is preliminary.", "primaryUses": [ "Investigational cardiac aging research", "Adjunctive use in Russian geriatric cardiology practice" ], "typicalDose": { "range": "not established", "unit": null, "frequency": "not established", "route": "oral (capsule) or intramuscular", "notes": "Russian supplement forms use 10 mg oral capsules once daily for 10–20 days as a cyclical bioregulator protocol." }, "evidenceLevel": "low", "sources": [ { "type": "review", "citation": "Khavinson VK, Malinin VV. \"Gerontological aspects of genome peptide regulation.\" Karger AG, Basel, 2005." }, { "type": "pubmed", "citation": "Anisimov VN, Khavinson VK. \"Peptide bioregulation of aging: results and prospects.\" Biogerontology, 2010;11:139-149. PMID: 19830585.", "pmid": "19830585" } ], "interactionCoverage": "unreviewed", "related": [ "epithalon", "cortagen", "ss-31" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "carnosine", "name": "Carnosine", "aliases": [ "L-Carnosine", "Beta-alanyl-L-histidine" ], "tier": "mid", "category": "longevity", "subcategory": "endogenous dipeptide", "class": "An endogenous dipeptide (beta-alanine + histidine) concentrated in skeletal muscle, brain, and heart tissue, with antioxidant, anti-glycation, and pH-buffering functions.", "tagline": "β-alanyl-L-histidine, the dipeptide concentrated in muscle and brain that buffers acid and resists glycation; as a supplement, small trials are mixed, and a 299-person trial found no general effect on physical performance.", "oneLiner": "A histidine-containing dipeptide synthesized by carnosine synthase, present at millimolar concentrations in skeletal muscle and brain, functioning as a pH buffer, metal chelator, anti-glycation agent, and reactive carbonyl scavenger.", "sequence": "β-Ala-His", "molecularFormula": "C9H14N4O3", "molecularWeight": 226.23, "halfLife": { "value": null, "unit": null, "range": "Rapidly degraded in blood by serum carnosinase", "notes": "Serum carnosinase splits carnosine into L-histidine and β-alanine (PMID 24137022); no half-life value in the abstracts read.", "source": { "type": "qualitative", "note": "a description with no figure; no half-life measurement is cited for it" } }, "fdaStatus": "supplement", "approvalDetails": "Sold as a dietary supplement. Not FDA-approved for any medical indication. Beta-alanine supplementation is the more common approach to raising tissue carnosine levels.", "mechanism": "Multi-functional: (1) pH buffer in exercising muscle via histidine imidazole ring; (2) chelates pro-oxidant transition metals (Cu²⁺, Zn²⁺, Fe²⁺); (3) scavenges reactive oxygen species and reactive carbonyl species (methylglyoxal, acrolein); (4) inhibits advanced glycation end-product (AGE) formation; (5) potential telomere-protective effects in fibroblast cultures.", "primaryUses": [ "Antioxidant and anti-aging supplement", "Anti-glycation agent research", "Neuroprotection studies (Alzheimer's, autism)", "Athletic performance (via beta-alanine/carnosine loading)" ], "typicalDose": { "range": "0.5–2", "unit": "g", "frequency": "daily (trial doses)", "route": "oral", "notes": "Trials used 500 mg to 2 g a day. The earlier note on beta-alanine doses had no source." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "O'Toole TE, et al. \"Effects of carnosine supplementation on physical endurance: a placebo-controlled randomized clinical trial.\" J Int Soc Sports Nutr, 2026;23(1):2679716. PMID: 42308284.", "pmid": "42308284" }, { "type": "pubmed", "citation": "Saadati S, et al. \"Carnosine Did Not Affect Vascular and Metabolic Outcomes in Patients with Prediabetes and Type 2 Diabetes: A 14-Week Randomized Controlled Trial.\" Nutrients, 2023;15(22). PMID: 38004228.", "pmid": "38004228" }, { "type": "pubmed", "citation": "Houjeghani S, et al. \"l-Carnosine supplementation attenuated fasting glucose, triglycerides, advanced glycation end products, and tumor necrosis factor-α levels in patients with type 2 diabetes: a double-blind placebo-controlled randomized clinical trial.\" Nutr Res, 2018;49:96-106. PMID: 29420997.", "pmid": "29420997" }, { "type": "pubmed", "citation": "Lombardi C, et al. \"Effects of oral administration of orodispersible levo-carnosine on quality of life and exercise performance in patients with chronic heart failure.\" Nutrition, 2015;31(1):72-8. PMID: 25287762.", "pmid": "25287762" }, { "type": "pubmed", "citation": "Araminia B, et al. \"L-Carnosine combination therapy for major depressive disorder: A randomized, double-blind, placebo-controlled trial.\" J Affect Disord, 2020;267:131-136. PMID: 32063564.", "pmid": "32063564" }, { "type": "pubmed", "citation": "Boldyrev AA, et al. \"Physiology and pathophysiology of carnosine.\" Physiol Rev, 2013;93(4):1803-45. PMID: 24137022.", "pmid": "24137022" }, { "type": "fda", "citation": "FDA. Drugs@FDA (openFDA): no application for carnosine. Read September 30, 2026." }, { "type": "other", "citation": "European Medicines Agency. Medicines register: no entry for carnosine. Read September 30, 2026." } ], "interactionCoverage": "studied", "related": [ "glutathione", "nad-plus", "epithalon" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-20", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "A food or supplement ingredient, not a drug; S0 is written for pharmacological substances. Supplements carry a separate risk: contamination with prohibited substances." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "A food or supplement ingredient, not a drug; S0 is written for pharmacological substances. Supplements carry a separate risk: contamination with prohibited substances." } ], "moleculeClass": "peptide" }, { "id": "carperitide", "name": "Carperitide", "aliases": [ "α-hANP", "human atrial natriuretic peptide", "recombinant hANP", "HANP", "Hanp" ], "tier": "full", "category": "cardiovascular", "subcategory": "Natriuretic peptide — guanylate cyclase-A (NPR-A) agonist", "class": "Recombinant α-human atrial natriuretic peptide (α-hANP; 28 residues), identical to endogenous ANP — approved in Japan since 1995 for acute heart failure; never approved by FDA or EMA.", "tagline": "⚠ Approved in Japan only (1995). Recombinant human ANP infused for acute heart failure and used in more than half of Japanese admissions in one study, but its outcome evidence conflicts: a propensity-matched analysis linked it to higher in-hospital mortality, and its randomised LASCAR-AHF trial stopped early without showing benefit.", "oneLiner": "Recombinant α-human atrial natriuretic peptide (α-hANP) — the 28-residue cardiac hormone secreted by atrial myocytes in response to atrial stretch — produced by chemical synthesis or recombinant methods. Approved in Japan since 1995 (Daiichi Sankyo) for acute heart failure. Never FDA-approved; no Western Phase 3 program. Acts via NPR-A / guanylate cyclase-A to produce vasodilation, natriuresis, and suppression of RAAS / SNS — the same receptor axis as nesiritide (which is recombinant BNP rather than ANP). Extensive Japanese real-world use: >30,000-patient pooled meta-analyses and multiple regional registries (COOPERATE-HF-J, REALITY-AHF, NARA-HF). 2024–2025 meta-analyses have raised concerns about increased in-hospital mortality versus placebo, while low-dose analyses (<0.02 μg/kg/min) have suggested benefit. No consensus; Japanese heart-failure guidelines (2019) continue to support selective use with acknowledged controversy.", "sequence": "SLRRSSCFGGRMDRIGAQSGLGCNSFRY (28 residues; disulfide bond Cys7-Cys23)", "molecularFormula": "C127H203N45O39S3", "molecularWeight": 3080.5, "halfLife": { "value": 3, "unit": "minutes", "range": "2.5 to 3.2 minutes (alpha-hANP in men; bolus and infusion)", "notes": "1986 human pharmacokinetic studies (PMIDs 2939312 and 2949138); always given as a continuous intravenous infusion, and partly removed by haemofiltration." }, "fdaStatus": "not-approved-us", "approvalDetails": "Japan: approved for acute heart failure in 1995 (as recorded in a 2016 review, PMID 26961205). Not FDA-approved (Drugs@FDA holds no application) and not in EMA's register of centrally authorised medicines (both read September 30, 2026).", "mechanism": "Agonist at natriuretic peptide receptor A (NPR-A / guanylyl cyclase A), raising cyclic GMP; produces vasodilation, natriuresis and diuresis and inhibits renin and aldosterone secretion. Plasma half-life about 2.5 to 3.2 minutes. Its main adverse effect, hypotension, follows from the vasodilation.", "primaryUses": [ "Acute heart failure (Japan-approved; used widely as adjunct to diuretics)", "Acute decompensated heart failure with volume overload (Japanese guideline-recommended)" ], "typicalDose": { "range": "0.01–0.1", "unit": "µg/kg/min (continuous IV infusion)", "frequency": "continuous infusion", "route": "intravenous", "notes": "Studies used 0.01 to 0.05 µg/kg/min in low-dose trials (72 hours), 0.025 to 0.05 as first-line therapy, and a median 0.085 (for a median 65 hours) in a 3,777-patient registry. Not available outside Japan." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "Honda S, et al. \"Effect of low-dose administration of carperitide for acute heart failure: the LASCAR-AHF trial.\" Eur Heart J Acute Cardiovasc Care, 2025;14(2):83-92. PMID: 39656827.", "pmid": "39656827" }, { "type": "pubmed", "citation": "Hata N, et al. \"Effects of carperitide on the long-term prognosis of patients with acute decompensated chronic heart failure: the PROTECT multicenter randomized controlled study.\" Circ J, 2008;72(11):1787-93. PMID: 18812677.", "pmid": "18812677" }, { "type": "pubmed", "citation": "Nogi K, et al. \"Effect of carperitide on the 1 year prognosis of patients with acute decompensated heart failure.\" ESC Heart Fail, 2022;9(2):1061-1070. PMID: 35118813.", "pmid": "35118813" }, { "type": "pubmed", "citation": "Matsue Y, et al. \"Carperitide Is Associated With Increased In-Hospital Mortality in Acute Heart Failure: A Propensity Score-Matched Analysis.\" J Card Fail, 2015;21(11):859-64. PMID: 25999241.", "pmid": "25999241" }, { "type": "pubmed", "citation": "Suwa M, et al. \"Multicenter prospective investigation on efficacy and safety of carperitide for acute heart failure in the 'real world' of therapy.\" Circ J, 2005;69(3):283-90. PMID: 15731532.", "pmid": "15731532" }, { "type": "pubmed", "citation": "Nomura F, et al. \"Multicenter prospective investigation on efficacy and safety of carperitide as a first-line drug for acute heart failure syndrome with preserved blood pressure: COMPASS: Carperitide Effects Observed Through Monitoring Dyspnea in Acute Decompensated Heart Failure Study.\" Circ J, 2008;72(11):1777-86. PMID: 18832779.", "pmid": "18832779" }, { "type": "pubmed", "citation": "Suzuki S, et al. \"Acute heart failure volume control multicenter randomized (AVCMA) trial: comparison of tolvaptan and carperitide.\" J Clin Pharmacol, 2013;53(12):1277-85. PMID: 24142853.", "pmid": "24142853" }, { "type": "pubmed", "citation": "Mizutani T, et al. \"Comparison of nitrite compounds and carperitide for initial treatment of acute decompensated heart failure.\" Int Heart J, 2011;52(2):114-8. PMID: 21483172.", "pmid": "21483172" }, { "type": "pubmed", "citation": "Sezai A, et al. \"Carperitide and atrial fibrillation after coronary bypass grafting: the Nihon University working group study of low-dose HANP infusion therapy during cardiac surgery trial for postoperative atrial fibrillation.\" Circ Arrhythm Electrophysiol, 2015;8(3):546-53. PMID: 25840580.", "pmid": "25840580" }, { "type": "pubmed", "citation": "Takahashi R, et al. \"Effects of continuous venovenous hemofiltration on the pharmacology of carperitide, a recombinant human atrial natriuretic peptide.\" Circ J, 2010;74(9):1888-94. PMID: 20668357.", "pmid": "20668357" }, { "type": "pubmed", "citation": "Gnädinger MP, et al. \"Plasma kinetics of synthetic alpha-human atrial natriuretic peptide in man.\" Miner Electrolyte Metab, 1986;12(5-6):371-4. PMID: 2949138.", "pmid": "2949138" }, { "type": "pubmed", "citation": "Yandle TG, et al. \"Metabolic clearance rate and plasma half life of alpha-human atrial natriuretic peptide in man.\" Life Sci, 1986;38(20):1827-33. PMID: 2939312.", "pmid": "2939312" }, { "type": "pubmed", "citation": "Torres-Courchoud I, et al. \"B-type natriuretic peptide and acute heart failure: Fluid homeostasis, biomarker and therapeutics.\" Rev Clin Esp (Barc), 2016;216(7):393-398. PMID: 26961205.", "pmid": "26961205" }, { "type": "fda", "citation": "FDA. Drugs@FDA (openFDA): no application for carperitide. Read September 30, 2026." }, { "type": "other", "citation": "European Medicines Agency. Medicines register (centrally authorised human medicines): no entry for carperitide. Read September 30, 2026." } ], "interactionCoverage": "none-found", "related": [ "nesiritide", "ularitide" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": "Japan (PMDA)", "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "cartalax", "name": "Cartalax", "aliases": [ "Ala-Glu-Asp", "AED tripeptide" ], "tier": "stub", "category": "longevity", "subcategory": "Khavinson short-chain bioregulator (cartilage)", "class": "A synthetic short tripeptide derived from cartilage tissue extract, developed by the Khavinson group as a \"cartilage bioregulator\".", "tagline": "A Khavinson tripeptide from cartilage tissue extract — proposed to support chondrocyte function and joint tissue homeostasis in aging and osteoarthritis models; mostly pre-clinical Russian-language evidence.", "oneLiner": "A Khavinson short-chain tripeptide (Ala-Glu-Asp) proposed to act as a tissue-specific transcriptional modulator in chondrocytes, supporting cartilage matrix synthesis and joint tissue homeostasis in osteoarthritis and joint-aging models.", "sequence": "Ala-Glu-Asp", "molecularFormula": "C11H17N3O8", "molecularWeight": 319.27, "halfLife": { "value": null, "unit": null, "range": "undetermined", "notes": "Pharmacokinetics not characterized in Western-standard studies." }, "fdaStatus": "research-only", "approvalDetails": "Not FDA-approved. Marketed in Russia as a bioregulator supplement.", "mechanism": "Proposed to bind chondrocyte DNA promoter regions and upregulate expression of collagen II, aggrecan, and related matrix proteins while downregulating matrix metalloproteinase expression. Western mechanistic validation is limited.", "primaryUses": [ "Investigational support in osteoarthritis and joint aging (Russian literature)", "Research into connective-tissue aging" ], "typicalDose": { "range": "not established", "unit": null, "frequency": "not established", "route": "oral (capsule)", "notes": "Typical supplement protocols use 10 mg daily for 10–20 days." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Khavinson VK, Kuznik BI, Ryzhak GA. \"Peptide bioregulators: a new class of geroprotectors. Message 1. Results of experimental studies.\" Adv Gerontol, 2012;25:696-708. PMID: 23734519.", "pmid": "23734519" } ], "interactionCoverage": "none-found", "related": [ "cortagen", "epithalon", "tb-500" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "cathelicidin", "name": "Cathelicidin", "aliases": [ "hCAP-18", "CAMP", "Cathelicidin Antimicrobial Peptide" ], "tier": "mid", "category": "immune", "subcategory": "host defense peptide", "class": "The human cathelicidin precursor protein (hCAP-18) from which LL-37 is cleaved, representing the only cathelicidin in humans, with central roles in innate immunity and vitamin D-mediated defense.", "tagline": "hCAP18, the precursor the body cuts to release LL-37: switched on by vitamin D, measured in blood and urine, never given as a treatment.", "oneLiner": "The human cathelicidin precursor protein, encoded by the CAMP gene and cleaved to release the antimicrobial peptide LL-37.", "sequence": "Precursor protein (170 aa); active peptide LL-37 is the C-terminal 37 residues", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": null, "range": "not measured in people in the sources read", "source": { "type": "none", "note": "searched PubMed on September 30, 2026; no half-life reported for hCAP18" } }, "fdaStatus": "research-only", "approvalDetails": "Not approved anywhere and never tested as a treatment; no application appears in Drugs@FDA. Its human studies measure it in blood and urine.", "mechanism": "hCAP-18 is stored in neutrophil secondary granules and released upon activation. Proteinase 3 cleaves the cathelin pro-domain to release LL-37, which: (1) disrupts microbial membranes via carpet/toroidal pore models; (2) neutralizes LPS endotoxin; (3) chemoattracts immune cells via FPR2/ALX receptor; (4) promotes wound healing via EGFR transactivation; (5) modulates TLR signaling. Expression upregulated by 1,25-dihydroxyvitamin D3 via VDR/RXR binding to the CAMP gene promoter.", "primaryUses": [ "Biomarker research (neutrophil production, infection)" ], "typicalDose": { "range": null, "unit": null, "frequency": null, "route": null, "notes": "Endogenous protein/peptide. Not administered therapeutically. LL-37 derivatives in preclinical development." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Jackmann N, et al. \"The human cathelicidin hCAP-18 in serum of children with haemato-oncological diseases.\" Br J Haematol, 2022;198(6):1023-1031. PMID: 35849644.", "pmid": "35849644" }, { "type": "pubmed", "citation": "Höpfinger A, et al. \"Circulating Levels of Cathelicidin Antimicrobial Peptide (CAMP) Are Affected by Oral Lipid Ingestion.\" Nutrients, 2023;15(13). PMID: 37447348.", "pmid": "37447348" }, { "type": "pubmed", "citation": "Chromek M, et al. \"The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection.\" Nat Med, 2006;12(6):636-41. PMID: 16751768.", "pmid": "16751768" }, { "type": "pubmed", "citation": "Aidoukovitch A, et al. \"Vitamin D triggers hCAP18/LL-37 production: Implications for LL-37-induced human osteoblast cytotoxicity.\" Biochem Biophys Res Commun, 2024;712-713:149962. PMID: 38642493.", "pmid": "38642493" }, { "type": "pubmed", "citation": "Vandamme D, et al. \"A comprehensive summary of LL-37, the factotum human cathelicidin peptide.\" Cell Immunol, 2012;280(1):22-35. PMID: 23246832.", "pmid": "23246832" }, { "type": "pubmed", "citation": "Liu PT, et al. \"Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response.\" Science, 2006;311(5768):1770-3. PMID: 16497887.", "pmid": "16497887" }, { "type": "other", "citation": "US FDA, Drugs@FDA (openFDA): no application for cathelicidin or hCAP18. Read September 30, 2026." } ], "interactionCoverage": "unreviewed", "related": [ "ll-37", "fk-13", "kr-12", "hnp-1", "hbd-2" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-20", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "protein", "moleculeClassBasis": "precursor protein" }, { "id": "cecropin", "name": "Cecropin", "aliases": [ "Cecropin A", "Cecropin B", "Cecropin P1" ], "tier": "stub", "category": "immune", "subcategory": "Antimicrobial peptide (AMP)", "class": "Cecropins are insect-derived antimicrobial peptides — among the first AMPs ever discovered (1981), establishing that innate immunity uses peptide antibiotics across the animal kingdom.", "tagline": "The insect immune system's first-line antibiotic — among the earliest AMPs discovered, proving innate immunity uses peptide weapons across the animal kingdom.", "oneLiner": "A family of 35-39-amino-acid cationic alpha-helical antimicrobial peptides from the cecropia moth that kill Gram-negative bacteria by membrane disruption without significant mammalian cell toxicity.", "sequence": "KWKLFKKIEKVGQNIRDGIIKAGPAVAVVGQATQIAK-amide (Cecropin A)", "molecularFormula": "C185H311N55O45", "molecularWeight": 4003.8, "halfLife": { "value": null, "unit": null, "range": "Minutes in serum", "notes": "Rapidly degraded by serum proteases. Research focuses on cecropin-melittin hybrid peptides for improved stability." }, "fdaStatus": "research-only", "approvalDetails": "Not approved. No cecropin derivatives have reached clinical trials as of 2026.", "mechanism": "Two-helix structure: N-terminal helix binds bacterial membrane surface, C-terminal helix inserts into the hydrophobic core. Acts via the 'carpet model' — lining membranes until threshold causes micelle-like dissolution. Highly selective for bacterial membranes.", "primaryUses": [ "Research: model AMP for innate immunity", "Template for hybrid AMP design", "Agricultural biotechnology: transgenic disease resistance" ], "typicalDose": { "range": "N/A", "unit": "N/A", "frequency": "N/A", "route": "research only", "notes": "Research MICs 1-10 mcM against Gram-negative pathogens." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "Steiner H, et al. \"Sequence and specificity of two antibacterial proteins involved in insect immunity.\" Nature. 1981;292(5820):246-248. PMID: 7019715.", "pmid": "7019715" }, { "type": "review", "citation": "Boman HG. \"Antibacterial peptides: basic facts and emerging concepts.\" J Intern Med. 2003;254(3):197-215. PMID: 12930229.", "pmid": "12930229" } ], "interactionCoverage": "unreviewed", "related": [ "magainin", "melittin", "ll-37", "cathelicidin" ], "lastReviewed": "2026-04-21", "publishedAt": "2026-04-21", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "cerebrolysin", "name": "Cerebrolysin", "aliases": [ "FPF-1070", "porcine brain peptide preparation" ], "tier": "full", "category": "cognitive", "subcategory": "neurotrophic peptide preparation", "class": "A mixture of low-molecular-weight peptides and free amino acids derived from porcine brain tissue by enzymatic digestion.", "tagline": "A pig-brain peptide mixture approved in about 50 countries for stroke and dementia; Cochrane found no survival benefit after stroke and more non-fatal serious adverse events.", "oneLiner": "A biologically standardized mixture of peptides (<10 kDa) and amino acids produced by proteolytic digestion of purified porcine brain tissue, with neurotrophic activity mimicking that of BDNF, GDNF, NGF, and CNTF, approved in 40+ countries for CNS disorders.", "sequence": null, "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": null, "range": "varies by component", "notes": "Mixture of compounds with diverse pharmacokinetics. Daily IV or IM dosing is standard." }, "fdaStatus": "not-approved-us", "approvalDetails": "Approved in 40+ countries including Austria, Germany, China, Russia, South Korea, and much of Eastern Europe. Indications include acute ischemic stroke, traumatic brain injury, vascular dementia, and Alzheimer's disease. NOT FDA-approved; manufactured by Ever Pharma (Austria).", "mechanism": "Multiple neurotrophic and neuroprotective effects: peptide components mimic the action of endogenous neurotrophic factors on TrkA, TrkB, and p75 receptors; amino acid components provide substrate for neurotransmitter synthesis. Demonstrated effects include enhanced synaptic plasticity, reduced excitotoxicity, reduced amyloid-β toxicity, and promotion of neurogenesis in animal models.", "primaryUses": [ "Acute ischemic stroke", "Traumatic brain injury", "Vascular dementia", "Alzheimer's disease (adjunct)", "Diabetic neuropathy" ], "typicalDose": { "range": "10–50", "unit": "mL/day", "frequency": "daily (course of 10–20 days)", "route": "intravenous or intramuscular", "notes": "Clinical protocols typically use 10–30 mL daily IV for 10–20 days, repeated in courses. Community use via IM injection mirrors this dosing pattern." }, "evidenceLevel": "high", "sources": [ { "type": "clinical-trial", "citation": "Heiss WD, et al. \"Cerebrolysin in patients with acute ischemic stroke in Asia: results of a double-blind, placebo-controlled randomized trial.\" Stroke, 2012;43(3):630-6. PMID: 22282884.", "pmid": "22282884" }, { "type": "review", "citation": "Ziganshina LE, et al. \"Cerebrolysin for acute ischaemic stroke.\" Cochrane Database Syst Rev, 2023;10(10):CD007026. PMID: 37818733.", "pmid": "37818733" }, { "type": "review", "citation": "Ziganshina LE, et al. \"Cerebrolysin for acute ischaemic stroke.\" Cochrane Database Syst Rev, 2017;4(4):CD007026. PMID: 28430363.", "pmid": "28430363" }, { "type": "pubmed", "citation": "Muresanu DF, et al. \"Cerebrolysin and Recovery After Stroke (CARS): A Randomized, Placebo-Controlled, Double-Blind, Multicenter Trial.\" Stroke, 2016;47(1):151-9. PMID: 26564102.", "pmid": "26564102" }, { "type": "pubmed", "citation": "Gharagozli K, et al. \"Efficacy and safety of Cerebrolysin treatment in early recovery after acute ischemic stroke: a randomized, placebo-controlled, double-blinded, multicenter clinical trial.\" J Med Life, 2017;10(3):153-160. PMID: 29075343.", "pmid": "29075343" }, { "type": "pubmed", "citation": "Guekht AB, et al. \"Cerebrolysin in vascular dementia: improvement of clinical outcome in a randomized, double-blind, placebo-controlled multicenter trial.\" J Stroke Cerebrovasc Dis, 2011;20(4):310-8. PMID: 20656516.", "pmid": "20656516" }, { "type": "pubmed", "citation": "Alvarez XA, et al. \"Efficacy and safety of Cerebrolysin in moderate to moderately severe Alzheimer's disease: results of a randomized, double-blind, controlled trial investigating three dosages of Cerebrolysin.\" Eur J Neurol, 2011;18(1):59-68. PMID: 20500802.", "pmid": "20500802" }, { "type": "clinical-trial", "citation": "Alvarez XA, et al. \"Combination treatment in Alzheimer's disease: results of a randomized, controlled trial with cerebrolysin and donepezil.\" Curr Alzheimer Res, 2011;8(5):583-91. PMID: 21679156.", "pmid": "21679156" }, { "type": "review", "citation": "Cui S, et al. \"Cerebrolysin for vascular dementia.\" Cochrane Database Syst Rev, 2019;2019(11). PMID: 31710397.", "pmid": "31710397" }, { "type": "review", "citation": "Thome J, et al. \"Safety profile of Cerebrolysin: clinical experience from dementia and stroke trials.\" Drugs Today (Barc), 2012;48 Suppl A:63-9. PMID: 22514795.", "pmid": "22514795" }, { "type": "pubmed", "citation": "Villarreal-Reyna G, et al. \"Cerebrolysin induces hair repigmentation associated to MART-1/Melan-A reactivation.\" Eur J Med Res, 2022;27(1):257. PMID: 36411485.", "pmid": "36411485" }, { "type": "pubmed", "citation": "Zhang C, et al. \"Cerebrolysin enhances neurogenesis in the ischemic brain and improves functional outcome after stroke.\" J Neurosci Res, 2010;88(15):3275-81. PMID: 20857512.", "pmid": "20857512" } ], "interactionCoverage": "none-found", "related": [ "semax", "selank", "dihexa", "noopept" ], "lastReviewed": "2026-09-26", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": "Austria and ~50 other countries", "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "blend", "moleculeClassBasis": "mixture of low-molecular-weight peptides" }, { "id": "cerluten", "name": "Cerluten", "aliases": [ "Lung peptide bioregulator (Khavinson)", "Lung cytomedine" ], "tier": "stub", "category": "longevity", "subcategory": "Khavinson lung-derived peptide bioregulator", "class": "A short peptide bioregulator derived from calf lung tissue, marketed in Russia as a cytomedine nutritional supplement within the Khavinson peptide bioregulator framework for respiratory and pulmonary aging support.", "tagline": "A Khavinson lung-derived short peptide bioregulator sold in Russia as a cytomedine supplement for respiratory aging. Like the rest of the Khavinson short-peptide family, supporting evidence is almost exclusively Russian-language and of low methodological rigor by Western standards; no independent replication, no FDA or EMA status, and no controlled clinical data.", "oneLiner": "One of roughly a dozen short peptide bioregulators extracted from bovine organ tissue in the Khavinson framework (Saint Petersburg Institute of Bioregulation and Gerontology). Cerluten is the lung-tissue-derived member of the series, marketed by Peptide Bioregulators Ltd. and other Russian suppliers as an oral capsule or tablet taken in courses for respiratory aging support. As with the broader Khavinson short-peptide literature, mechanistic claims center on putative \"tissue-specific\" gene-expression modulation, but the supporting literature is limited to Russian-language studies from the Khavinson group and close collaborators, with minimal independent replication.", "sequence": "Not definitively disclosed; Khavinson framework typically posits short 2–4 residue active peptides", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": null, "range": "Not characterized", "notes": "No pharmacokinetic data published in peer-reviewed Western literature." }, "fdaStatus": "not-approved-us", "approvalDetails": "Not FDA- or EMA-approved. Sold in Russia and several CIS states as a nutraceutical cytomedine supplement, not as a registered medicine. Distributed by Peptide Bioregulators Ltd. (Saint Petersburg) and affiliated Khavinson-network suppliers.", "mechanism": "Proposed mechanism within the Khavinson bioregulator framework: short peptides cross cell membranes, enter the nucleus, and bind regulatory DNA regions in a tissue-specific fashion to modulate transcription of aging-related genes in the source tissue (here, lung). Molecular validation of this mechanism at the level of specific target genes or transcription-factor binding is minimal and has not been independently replicated outside the Khavinson group. Mechanism should be regarded as speculative.", "primaryUses": [ "Respiratory aging support (Russian nutraceutical positioning)", "Post-pulmonary-illness recovery (Russian clinical use)" ], "typicalDose": { "range": "1–2 capsules", "unit": null, "frequency": "1–2 times daily in 20–30 day courses", "route": "oral", "notes": "Russian nutraceutical dosing; no human pharmacokinetic or controlled clinical data support this regimen as efficacious. Courses are typically repeated 2–4 times yearly." }, "evidenceLevel": "low", "sources": [ { "type": "other", "citation": "Khavinson VK. \"Peptides and Ageing.\" Neuroendocrinol Lett, 2002;23 Suppl 3:1-144 (monograph covering the full Khavinson bioregulator framework)." }, { "type": "review", "citation": "Anisimov VN, Khavinson VK. \"Peptide bioregulation of aging: results and prospects.\" Biogerontology, 2010;11:139-149. PMID: 19830585.", "pmid": "19830585" } ], "interactionCoverage": "none-found", "related": [ "epithalon", "pinealon", "endoluten", "visoluten" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": "", "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "cetrorelix", "name": "Cetrorelix", "aliases": [ "Cetrotide" ], "tier": "mid", "category": "sexual-health", "subcategory": "GnRH antagonist", "class": "Synthetic decapeptide GnRH-receptor antagonist used in IVF to prevent premature LH surges during controlled ovarian stimulation.", "tagline": "Merck Serono's Cetrotide — a GnRH antagonist used during IVF controlled ovarian stimulation to block premature LH surges. Unlike GnRH agonists, produces immediate gonadotropin suppression without a flare, shortening IVF cycles.", "oneLiner": "A synthetic decapeptide GnRH-receptor antagonist with five non-natural amino acid substitutions, producing rapid competitive blockade of pituitary GnRH receptors. Used in IVF controlled ovarian stimulation to prevent premature LH surges in a simpler and shorter protocol than GnRH-agonist downregulation. FDA-approved as Cetrotide in 2000; the first GnRH antagonist approved for reproductive medicine.", "sequence": "Ac-D-Nal(2)-D-pClPhe-D-Pal(3)-Ser-Tyr-D-Cit-Leu-Arg-Pro-D-Ala-NH2", "molecularFormula": "C70H92ClN17O14", "molecularWeight": 1431, "halfLife": { "value": 20.6, "unit": "hours", "range": "5.0 hours after a single 0.25 mg dose, 20.6 hours with 0.25 mg daily for 14 days, 62.8 hours after a single 3 mg dose (geometric means, label Table 1)", "source": { "type": "label", "ref": "Cetrotide (cetrorelix acetate for injection) prescribing information: indications, dosage, contraindications, precautions, adverse reactions and pharmacokinetics (DailyMed SPL version 18, effective September 22, 2025; read October 1, 2026)" } }, "fdaStatus": "approved", "approvalDetails": "Cetrotide, NDA 021197, approved August 11, 2000, for the inhibition of premature LH surges in women undergoing controlled ovarian stimulation (Drugs@FDA and the label, read October 1, 2026).", "mechanism": "Competitive antagonism at pituitary GnRH receptors — rapid onset blocks endogenous GnRH binding within hours, immediately suppressing LH and FSH release without the initial agonist flare. Effect wanes rapidly after discontinuation, permitting hCG trigger for ovulation.", "primaryUses": [ "Prevention of premature LH surge during IVF controlled ovarian stimulation" ], "typicalDose": { "range": "0.25", "unit": "mg", "frequency": "once daily from stimulation day 5 or 6 until the hCG day", "route": "subcutaneous", "notes": "Cetrotide label: 0.25 mg subcutaneously once daily, started on stimulation day 5 (morning or evening) or day 6 (morning) and continued until the day of hCG administration; may be self-injected after instruction. Withhold hCG if the ovarian response is excessive." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Cetrotide (cetrorelix acetate for injection) prescribing information: indications, dosage, contraindications, precautions, adverse reactions and pharmacokinetics (DailyMed SPL version 18, effective September 22, 2025; read October 1, 2026)." }, { "type": "pubmed", "citation": "Olivennes F, et al. \"Safety and efficacy of a 3 mg dose of the GnRH antagonist cetrorelix in preventing premature LH surges: report of two large multicentre, multinational, phase IIIb clinical experiences.\" Reprod Biomed Online, 2003;6(4):432-8. PMID: 12831588.", "pmid": "12831588" }, { "type": "pubmed", "citation": "Olivennes F, et al. \"Prospective, randomized, controlled study of in vitro fertilization-embryo transfer with a single dose of a luteinizing hormone-releasing hormone (LH-RH) antagonist (cetrorelix) or a depot formula of an LH-RH agonist (triptorelin).\" Fertil Steril, 2000;73(2):314-20. PMID: 10685535.", "pmid": "10685535" }, { "type": "pubmed", "citation": "Ludwig M, et al. \"Significant reduction of the incidence of ovarian hyperstimulation syndrome (OHSS) by using the LHRH antagonist Cetrorelix (Cetrotide) in controlled ovarian stimulation for assisted reproduction.\" Arch Gynecol Obstet, 2000;264(1):29-32. PMID: 10985616.", "pmid": "10985616" }, { "type": "pubmed", "citation": "Kåss AS, et al. \"Short-term treatment with a gonadotropin-releasing hormone antagonist, cetrorelix, in rheumatoid arthritis (AGRA): a randomized, double-blind, placebo-controlled study.\" Scand J Rheumatol, 2014;43(1):22-7. PMID: 24182325.", "pmid": "24182325" }, { "type": "pubmed", "citation": "Al-Inany HG, et al. \"Gonadotrophin-releasing hormone antagonists for assisted reproductive technology.\" Cochrane Database Syst Rev, 2016;4(4):CD001750. PMID: 27126581.", "pmid": "27126581" } ], "interactionCoverage": "partial", "related": [ "ganirelix", "degarelix", "gonadorelin", "follitropin-alfa", "hcg" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "A GnRH antagonist: S2.2.1 covers GnRH and its agonist analogues, not antagonists." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "A GnRH antagonist: S2.2.1 covers GnRH and its agonist analogues, not antagonists." } ], "moleculeClass": "peptide" }, { "id": "cgrp", "name": "CGRP", "aliases": [ "Calcitonin Gene-Related Peptide", "α-CGRP", "β-CGRP" ], "tier": "mid", "category": "cardiovascular", "subcategory": "neuropeptide / vasodilator", "class": "A 37-amino-acid neuropeptide produced by alternative splicing of the calcitonin gene, the most potent known endogenous vasodilator and a central mediator of migraine pathophysiology.", "tagline": "The vasodilating neuropeptide behind migraine attacks: infused, it triggers them, and drugs that block it now prevent them.", "oneLiner": "A 37-amino-acid sensory neuropeptide from the calcitonin gene that strongly widens vessels and acts on the CLR-RAMP1 receptor.", "sequence": "ACDTATCVTHRLAGLLSRSGGVVKNNFVPTNVGSKAF-NH2", "molecularFormula": "C161H250N44O47S4", "molecularWeight": 3789.4, "halfLife": { "value": null, "unit": null, "range": "not reported in the sources read", "source": { "type": "none", "note": "searched on September 30, 2026; no half-life reported in the sources read" } }, "fdaStatus": "research-only", "approvalDetails": "Not a medicine anywhere; no application appears in Drugs@FDA. Drugs that block it are approved separately, including erenumab (Aimovig), a CGRP receptor antagonist for migraine prevention in adults.", "mechanism": "Released from trigeminal C-fibers during cortical spreading depression (migraine aura) or via trigeminovascular activation. Binds the CLR/RAMP1 receptor complex (calcitonin receptor-like receptor complexed with RAMP1), activating Gs → cAMP. Causes potent meningeal arteriolar vasodilation, mast cell degranulation, plasma protein extravasation, and peripheral and central sensitization. The most potent vasodilator known: 10× more potent than prostaglandins.", "primaryUses": [ "Research challenge agent (migraine)" ], "typicalDose": { "range": null, "unit": null, "frequency": null, "route": null, "notes": "Endogenous neuropeptide. IV CGRP infusion used experimentally to provoke migraine in research (1.5 mcg/min × 20 min). Not a therapeutic." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Ashina H, et al. \"Hypersensitivity to Calcitonin Gene-Related Peptide in Post-Traumatic Headache.\" Ann Neurol, 2020;88(6):1220-1228. PMID: 32959458.", "pmid": "32959458" }, { "type": "pubmed", "citation": "Jäger K, et al. \"Calcitonin gene-related peptide (CGRP) causes redistribution of blood flow in humans.\" Eur J Clin Pharmacol, 1990;39(5):491-4. PMID: 2076743.", "pmid": "2076743" }, { "type": "pubmed", "citation": "Juul R, et al. \"Calcitonin gene-related peptide (human alpha-CGRP) counteracts vasoconstriction in human subarachnoid haemorrhage.\" Neurosci Lett, 1994;170(1):67-70. PMID: 8041516.", "pmid": "8041516" }, { "type": "pubmed", "citation": "Edvinsson L, et al. \"CGRP as the target of new migraine therapies - successful translation from bench to clinic.\" Nat Rev Neurol, 2018;14(6):338-350. PMID: 29691490.", "pmid": "29691490" }, { "type": "pubmed", "citation": "Russell FA, et al. \"Calcitonin gene-related peptide: physiology and pathophysiology.\" Physiol Rev, 2014;94(4):1099-142. PMID: 25287861.", "pmid": "25287861" }, { "type": "fda-pi", "citation": "AIMOVIG (erenumab-aooe) injection Prescribing Information, sections 1 (DailyMed version 25, effective July 14, 2026; read September 30, 2026)." }, { "type": "other", "citation": "US FDA, Drugs@FDA (openFDA): no application for CGRP. Read September 30, 2026." } ], "interactionCoverage": "unreviewed", "related": [ "calcitonin", "adrenomedullin", "substance-p" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-20", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "cholecystokinin", "name": "Cholecystokinin", "aliases": [ "CCK", "CCK-8", "CCK-33", "CCK-58", "Pancreozymin" ], "tier": "mid", "category": "metabolic", "subcategory": "Endogenous gut-brain peptide", "class": "Cholecystokinin is the prototypical satiety hormone — the first gut peptide shown to reduce food intake. It bridges the metabolic and cognitive categories as both a GI hormone and a brain neuropeptide.", "tagline": "The gut hormone that empties the gallbladder after meals; its octapeptide, sincalide (Kinevac), is FDA-approved for diagnostic tests.", "oneLiner": "A family of gut and brain peptides acting on CCK1 and CCK2 receptors; its C-terminal octapeptide is approved as sincalide for diagnostic use.", "sequence": "DYMGWMDF-amide (CCK-8, the bioactive C-terminal octapeptide; sulfated on Tyr7)", "molecularFormula": "C49H62N10O16S2", "molecularWeight": 1143.2, "halfLife": { "value": null, "unit": null, "range": "not reported in the sources read", "source": { "type": "none", "note": "searched on September 30, 2026; no half-life reported in the sources read" } }, "fdaStatus": "diagnostic", "approvalDetails": "FDA-approved as Kinevac (sincalide), NDA 017697, the synthetic C-terminal octapeptide of cholecystokinin, to contract the gallbladder for imaging or bile sampling, to stimulate pancreatic secretion with secretin, and to speed a barium meal. Not approved as a treatment.", "mechanism": "Binds CCK1R (peripheral gut — mediates satiety, gallbladder contraction, pancreatic enzyme secretion) and CCK2R (primarily CNS — modulates anxiety, pain perception, and memory). CCK1R activation on vagal afferents transmits the satiety signal to the nucleus tractus solitarius.", "primaryUses": [ "Gallbladder and pancreatic function testing (sincalide)" ], "typicalDose": { "range": "0.02", "unit": "mcg/kg", "frequency": "single diagnostic dose", "route": "IV (sincalide only)", "notes": "Sincalide 0.02 mcg/kg IV is used diagnostically for cholecystography. Not used therapeutically for satiety." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "KINEVAC (sincalide) for injection Prescribing Information, sections 1, 4, 6 and 11 (DailyMed version 13, effective October 18, 2023; read September 30, 2026)." }, { "type": "pubmed", "citation": "Byrnes DJ, et al. \"Cholecystokinin and gallbladder contraction: effect of CCK infusion.\" Peptides, 1981;2 Suppl 2:259-62. PMID: 6283495.", "pmid": "6283495" }, { "type": "pubmed", "citation": "Rohde U, et al. \"Cholecystokinin-Induced Gallbladder Emptying and Metformin Elicit Additive Glucagon-Like Peptide-1 Responses.\" J Clin Endocrinol Metab, 2016;101(5):2076-83. PMID: 27003305.", "pmid": "27003305" }, { "type": "pubmed", "citation": "Lange AH, et al. \"Exogenous Glucagon-like Peptide 2 Counteracts Exogenous Cholecystokinin-induced Gallbladder Contraction in Healthy Men.\" J Clin Endocrinol Metab, 2024;110(1):123-129. PMID: 38888179.", "pmid": "38888179" }, { "type": "pubmed", "citation": "Rehfeld JF. \"Cholecystokinin-From Local Gut Hormone to Ubiquitous Messenger.\" Front Endocrinol (Lausanne), 2017;8:47. PMID: 28450850.", "pmid": "28450850" }, { "type": "pubmed", "citation": "Gibbs J, et al. \"Cholecystokinin decreases food intake in rats.\" J Comp Physiol Psychol, 1973;84(3):488-95. PMID: 4745816.", "pmid": "4745816" }, { "type": "other", "citation": "US FDA, Drugs@FDA (openFDA): KINEVAC (sincalide), NDA 017697, Bracco, prescription. Read September 30, 2026." } ], "interactionCoverage": "unreviewed", "related": [ "pyy", "ghrelin", "neuropeptide-y", "glp-2", "semaglutide" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-21", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Its octapeptide form, sincalide, is FDA-approved as a diagnostic agent; S0 speaks of approval for therapeutic use." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Its octapeptide form, sincalide, is FDA-approved as a diagnostic agent; S0 speaks of approval for therapeutic use." } ], "moleculeClass": "peptide", "statusVerified": { "date": "2026-09-30", "source": "Drugs@FDA NDA 017697 (Kinevac, Bracco); Kinevac label: a synthetically prepared C-terminal octapeptide of cholecystokinin" } }, { "id": "chonluten", "name": "Chonluten", "aliases": [ "Glu-Asp-Gly", "EDG tripeptide" ], "tier": "stub", "category": "longevity", "subcategory": "Khavinson short-chain bioregulator (respiratory mucosa)", "class": "A synthetic short tripeptide derived from lung tissue extract, developed by the Khavinson group as a \"bronchial / respiratory bioregulator\".", "tagline": "A Khavinson tripeptide studied for bronchial epithelium regeneration and anti-inflammatory effects in the respiratory tract — evidence base is Russian-language and preliminary.", "oneLiner": "A Khavinson short-chain tripeptide (Glu-Asp-Gly) proposed to modulate gene expression in bronchial epithelium and alveolar cells, with reported anti-inflammatory and epithelial-regenerative effects in Russian animal-model and early clinical literature in chronic respiratory disease.", "sequence": "Glu-Asp-Gly", "molecularFormula": "C11H17N3O8", "molecularWeight": 319.27, "halfLife": { "value": null, "unit": null, "range": "undetermined", "notes": "Pharmacokinetics not characterized in Western-standard studies." }, "fdaStatus": "research-only", "approvalDetails": "Not FDA-approved. Marketed in Russia as a bioregulator supplement.", "mechanism": "Proposed to bind promoter regions in bronchial and alveolar cells, upregulating expression of genes that support mucosal repair and downregulating pro-inflammatory signaling. Animal studies from the Khavinson group report reduced airway inflammation in experimental models.", "primaryUses": [ "Investigational support in chronic respiratory disease (Russian literature)", "Research into respiratory aging" ], "typicalDose": { "range": "not established", "unit": null, "frequency": "not established", "route": "oral (capsule) or intranasal", "notes": "Typical supplement dosing is 10 mg daily in short cyclical courses." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Khavinson VK, Kuznik BI, Ryzhak GA. \"Peptide bioregulators: a new class of geroprotectors. Message 2. Clinical studies.\" Adv Gerontol, 2013;26:20-37. PMID: 24003726.", "pmid": "24003726" } ], "interactionCoverage": "unreviewed", "related": [ "bronchogen", "cortagen", "epithalon" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "cjc-1295", "name": "CJC-1295", "aliases": [ "CJC-1295 DAC", "CJC-1295 with DAC", "DAC:GRF", "Drug Affinity Complex:GRF" ], "tier": "full", "category": "growth-hormone", "subcategory": "long-acting GHRH analog", "class": "Modified 29-amino-acid GHRH analog conjugated to a Drug Affinity Complex (DAC) for extended half-life.", "tagline": "A long-acting GHRH analog engineered with a DAC linker that binds serum albumin, extending half-life from minutes to approximately 8 days.", "oneLiner": "A tetrasubstituted GHRH(1-29) analog (D-Ala2, Gln8, Ala15, Leu27) with a maleimidopropionyl-Lys30 DAC linker that covalently binds serum albumin, producing sustained GH elevation over roughly a week per dose.", "sequence": "H-Tyr-D-Ala-Asp-Ala-Ile-Phe-Thr-Gln-Ser-Tyr-Arg-Lys-Val-Leu-Ala-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Leu-Ser-Arg-Lys(MPA)-NH2", "molecularFormula": "C165H269N47O46", "molecularWeight": 3647.24, "halfLife": { "value": null, "unit": null, "range": "5.8–8.1 days (with DAC)", "notes": "Estimated in healthy adults after single subcutaneous injections (2006). The 29-amino-acid peptide without the albumin binder, often sold under the same name, was not studied in those trials and acts for a much shorter time." }, "fdaStatus": "discontinued", "approvalDetails": "Not approved. Tested in two small studies in healthy adults (2006). Its US compounding nomination was withdrawn; FDA records serious adverse events associated with it, including increased heart rate and a systemic vasodilatory reaction.", "mechanism": "GHRH(1-29) analogue with four substitutions and a maleimidopropionamide-lysine that bonds covalently to albumin after injection, keeping it in circulation for days. In healthy adults it raised growth hormone for six days or more and IGF-1 for up to 11 days, with growth hormone pulses preserved and trough levels raised.", "primaryUses": [ "Growth hormone axis research", "Community use for GH/IGF-1 elevation (off-label)", "Visceral fat loss research (originally developed for HIV lipodystrophy)" ], "typicalDose": { "range": "1–2", "unit": "mg", "frequency": "once or twice weekly", "route": "subcutaneous", "notes": "Community figures only. The human studies used per-kilogram doses, with 30 to 60 µg/kg best tolerated (about 2 to 4 mg at 70 kg). Often sold blended with ipamorelin, a combination no trial has tested." }, "evidenceLevel": "medium", "sources": [ { "type": "clinical-trial", "citation": "Teichman SL, et al. \"Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults.\" J Clin Endocrinol Metab, 2006;91(3):799-805. PMID: 16352683.", "pmid": "16352683" }, { "type": "pubmed", "citation": "Ionescu M, et al. \"Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog.\" J Clin Endocrinol Metab, 2006;91(12):4792-7. PMID: 17018654.", "pmid": "17018654" }, { "type": "pubmed", "citation": "Sackmann-Sala L, et al. \"Activation of the GH/IGF-1 axis by CJC-1295, a long-acting GHRH analog, results in serum protein profile changes in normal adult subjects.\" Growth Horm IGF Res, 2009;19(6):471-7. PMID: 19386527.", "pmid": "19386527" }, { "type": "pubmed", "citation": "Van Hout MC, et al. \"Netnography of Female Use of the Synthetic Growth Hormone CJC-1295: Pulses and Potions.\" Subst Use Misuse, 2016;51(1):73-84. PMID: 26771670.", "pmid": "26771670" }, { "type": "pubmed", "citation": "Jetté L, et al. \"Human growth hormone-releasing factor (hGRF)1-29-albumin bioconjugates activate the GRF receptor on the anterior pituitary in rats: identification of CJC-1295 as a long-lasting GRF analog.\" Endocrinology, 2005;146(7):3052-8. PMID: 15817669.", "pmid": "15817669" }, { "type": "pubmed", "citation": "Alba M, et al. \"Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse.\" Am J Physiol Endocrinol Metab, 2006;291(6):E1290-4. PMID: 16822960.", "pmid": "16822960" }, { "type": "pubmed", "citation": "Timms M, et al. \"A method for confirming CJC-1295 abuse in equine plasma samples by LC-MS/MS.\" Drug Test Anal, 2019;11(8):1248-1257. PMID: 30938069.", "pmid": "30938069" }, { "type": "pubmed", "citation": "Henninge J, et al. \"Identification of CJC-1295, a growth-hormone-releasing peptide, in an unknown pharmaceutical preparation.\" Drug Test Anal, 2010;2(11-12):647-50. PMID: 21204297.", "pmid": "21204297" }, { "type": "other", "citation": "U.S. Food and Drug Administration. Certain bulk drug substances for use in compounding that may present significant safety risks (CJC-1295, among nominations withdrawn). Content current as of April 22, 2026; read September 26, 2026." } ], "interactionCoverage": "partial", "related": [ "ipamorelin", "sermorelin", "tesamorelin", "mod-grf-1-29" ], "lastReviewed": "2026-09-26", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.2.4", "named": true, "wording": "CJC-1295", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Named alongside CJC-1293 as a GHRH analogue." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.2.4", "named": true, "wording": "CJC-1295", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Named alongside CJC-1293 as a GHRH analogue." } ], "moleculeClass": "peptide" }, { "id": "cnp", "name": "CNP", "aliases": [ "C-type Natriuretic Peptide", "Vosoritide precursor" ], "tier": "mid", "category": "cardiovascular", "subcategory": "endogenous natriuretic peptide", "class": "A 22-amino-acid natriuretic peptide primarily produced by vascular endothelium and chondrocytes, with vasodilatory and bone growth-promoting effects distinct from ANP and BNP.", "tagline": "The third natriuretic peptide — a vascular and skeletal growth factor whose analog vosoritide (Voxzogo) is FDA-approved for achondroplasia, and the endogenous cartilage growth signal.", "oneLiner": "A 22-amino-acid member of the natriuretic peptide family that acts through NPR-B (guanylyl cyclase B) rather than NPR-A, with primary roles in vascular homeostasis and endochondral bone growth rather than cardiac volume regulation.", "sequence": "GLSKGCFGLKLDRIGSMSGLGC (Cys6–Cys22 disulfide)", "molecularFormula": "C92H151N27O28S2", "molecularWeight": 2197.5, "halfLife": { "value": null, "unit": null, "range": "not reported in the sources read", "source": { "type": "none", "note": "searched PubMed on October 1, 2026; no human half-life figure in the sources read" } }, "fdaStatus": "research-only", "approvalDetails": "Not approved as a drug; no application for CNP itself appears in Drugs@FDA (read October 1, 2026). Its analogue vosoritide (Voxzogo) was approved under NDA 214938 on November 19, 2021 for achondroplasia.", "mechanism": "Binds NPR-B (natriuretic peptide receptor B), a membrane-bound guanylyl cyclase distinct from the ANP/BNP receptor NPR-A. In vasculature: cGMP-mediated vasodilation and anti-proliferative effects. In growth plate cartilage: cGMP antagonizes FGFR3 overactivation (the achondroplasia defect) by inhibiting the MAPK/ERK pathway, restoring normal chondrocyte proliferation and differentiation.", "primaryUses": [ "Achondroplasia treatment (via vosoritide analog)", "Skeletal growth plate biology", "Vascular homeostasis research", "Natriuretic peptide system studies" ], "typicalDose": { "range": null, "unit": null, "frequency": null, "route": null, "notes": "Not a medicine. Vosoritide, the approved analogue, is given once daily subcutaneously to children with achondroplasia." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Savarirayan R, et al. \"Once-daily, subcutaneous vosoritide therapy in children with achondroplasia: a randomised, double-blind, phase 3, placebo-controlled, multicentre trial.\" Lancet, 2020;396(10252):684-692. PMID: 32891212.", "pmid": "32891212" }, { "type": "pubmed", "citation": "Savarirayan R, et al. \"Safe and persistent growth-promoting effects of vosoritide in children with achondroplasia: 2-year results from an open-label, phase 3 extension study.\" Genet Med, 2021;23(12):2443-2447. PMID: 34341520.", "pmid": "34341520" }, { "type": "pubmed", "citation": "Savarirayan R, et al. \"Vosoritide therapy in children with achondroplasia aged 3-59 months: a multinational, randomised, double-blind, placebo-controlled, phase 2 trial.\" Lancet Child Adolesc Health, 2024;8(1):40-50. PMID: 37984383.", "pmid": "37984383" }, { "type": "pubmed", "citation": "Savarirayan R, et al. \"C-Type Natriuretic Peptide Analogue Therapy in Children with Achondroplasia.\" N Engl J Med, 2019;381(1):25-35. PMID: 31269546.", "pmid": "31269546" }, { "type": "pubmed", "citation": "Dickinson YA, et al. \"C-type natriuretic peptide (CNP): The cardiovascular system and beyond.\" Pharmacol Ther, 2024;262:108708. PMID: 39154787.", "pmid": "39154787" }, { "type": "pubmed", "citation": "Potter LR, et al. \"Natriuretic peptides, their receptors, and cyclic guanosine monophosphate-dependent signaling functions.\" Endocr Rev, 2006;27(1):47-72. PMID: 16291870.", "pmid": "16291870" }, { "type": "pubmed", "citation": "Barr CS, et al. \"C-type natriuretic peptide.\" Peptides, 1996;17(7):1243-51. PMID: 8959763.", "pmid": "8959763" } ], "interactionCoverage": "unreviewed", "related": [ "bnp", "anp", "nesiritide" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-20", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "colistin", "name": "Colistin", "aliases": [ "Polymyxin E", "Colistimethate Sodium", "CMS" ], "tier": "mid", "category": "immune", "subcategory": "lipopeptide antibiotic", "class": "A cyclic lipopeptide antibiotic closely related to polymyxin B, used as a last-resort agent against multidrug-resistant gram-negative infections.", "tagline": "Polymyxin B's sibling — a cyclic lipopeptide antibiotic revived from the 1950s as the ultimate weapon against pan-drug-resistant gram-negative bacteria, despite significant nephrotoxicity.", "oneLiner": "A cyclic lipopeptide antibiotic (polymyxin E) administered as the inactive prodrug colistimethate sodium (CMS), with the same LPS-disrupting mechanism as polymyxin B but different pharmacokinetics due to prodrug conversion.", "sequence": "Cyclic heptapeptide core + tripeptide side chain + 6-methyloctanoyl tail (differs from polymyxin B at position 6: D-Leu vs D-Phe)", "molecularFormula": "C52H98N16O13", "molecularWeight": 1155.4, "halfLife": { "value": 2.5, "unit": "hours", "range": "2 to 3 hours after intravenous or intramuscular colistimethate", "source": { "type": "label", "ref": "Coly-Mycin M Parenteral (colistimethate sodium) prescribing information, Dosage and Administration, Warnings and Clinical Pharmacology (DailyMed SPL version 27, effective June 8, 2026; read October 1, 2026)" } }, "fdaStatus": "approved", "approvalDetails": "Coly-Mycin M Parenteral (colistimethate sodium), NDA 050108, originally approved June 4, 1970 (Drugs@FDA, read October 1, 2026), for infections due to sensitive gram-negative bacilli, particularly Pseudomonas aeruginosa. The label's maximum is 5 mg/kg a day of colistin base.", "mechanism": "Same as polymyxin B: cationic peptide ring displaces divalent cations from LPS, destabilizing the gram-negative outer membrane and causing cell lysis. Also binds and neutralizes circulating endotoxin. Administered as the prodrug CMS (colistimethate), which is hydrolyzed to active colistin in vivo.", "primaryUses": [ "Multidrug-resistant gram-negative infections", "Cystic fibrosis chronic Pseudomonas suppression (inhaled)", "Carbapenem-resistant Enterobacteriaceae", "Ventilator-associated pneumonia (MDR pathogens)" ], "typicalDose": { "range": "2.5-5", "unit": "mg/kg/day of colistin base", "frequency": "in 2 to 4 divided doses", "route": "intravenous or intramuscular", "notes": "Coly-Mycin M label for adults and children with normal kidney function; never more than 5 mg/kg a day, reduced for kidney impairment, and based on ideal body weight in obesity." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Coly-Mycin M Parenteral (colistimethate sodium) prescribing information, Dosage and Administration, Warnings and Clinical Pharmacology (DailyMed SPL version 27, effective June 8, 2026; read October 1, 2026)." }, { "type": "pubmed", "citation": "Paul M, et al. \"Colistin alone versus colistin plus meropenem for treatment of severe infections caused by carbapenem-resistant Gram-negative bacteria: an open-label, randomised controlled trial.\" Lancet Infect Dis, 2018;18(4):391-400. PMID: 29456043.", "pmid": "29456043" }, { "type": "pubmed", "citation": "Kaye KS, et al. \"Efficacy and safety of sulbactam-durlobactam versus colistin for the treatment of patients with serious infections caused by Acinetobacter baumannii-calcoaceticus complex: a multicentre, randomised, active-controlled, phase 3, non-inferiority clinical trial (ATTACK).\" Lancet Infect Dis, 2023;23(9):1072-1084. PMID: 37182534.", "pmid": "37182534" }, { "type": "pubmed", "citation": "Haworth CS, et al. \"Inhaled colistimethate sodium in patients with bronchiectasis and Pseudomonas aeruginosa infection: results of PROMIS-I and PROMIS-II, two randomised, double-blind, placebo-controlled phase 3 trials assessing safety and efficacy over 12 months.\" Lancet Respir Med, 2024;12(10):787-798. PMID: 39270696.", "pmid": "39270696" }, { "type": "pubmed", "citation": "Motsch J, et al. \"RESTORE-IMI 1: A Multicenter, Randomized, Double-blind Trial Comparing Efficacy and Safety of Imipenem/Relebactam vs Colistin Plus Imipenem in Patients With Imipenem-nonsusceptible Bacterial Infections.\" Clin Infect Dis, 2020;70(9):1799-1808. PMID: 31400759.", "pmid": "31400759" }, { "type": "pubmed", "citation": "Nation RL, et al. \"Colistin in the 21st century.\" Curr Opin Infect Dis, 2009;22(6):535-43. PMID: 19797945.", "pmid": "19797945" } ], "interactionCoverage": "label", "related": [ "polymyxin-b", "daptomycin", "ll-37" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-20", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "collagen-peptides", "name": "Collagen Peptides", "aliases": [ "Hydrolyzed Collagen", "Collagen Hydrolysate", "Collagen Protein" ], "tier": "mid", "category": "cosmetic", "subcategory": "bioactive food-derived peptide", "class": "Enzymatically hydrolyzed collagen fragments (typically 2–20 amino acids) derived from bovine, marine, porcine, or chicken collagen, marketed as dietary supplements for skin, joint, and bone health.", "tagline": "Hydrolysed collagen taken by mouth, a mixture of short peptides rather than one molecule. Randomised trials at 2.5 to 15 g a day report better skin elasticity and hydration, higher bone mineral density in postmenopausal women, less activity-related knee pain. A dietary supplement, not an approved medicine.", "oneLiner": "Enzymatically hydrolysed collagen from cattle, fish, pigs or chickens, absorbed as short peptides including the tripeptide Gly-Pro-Hyp and sold as a dietary supplement. Randomised trials test individual makers' preparations at 2.5 to 15 g a day for skin, bone, joint, muscle and tendon outcomes.", "sequence": "Heterogeneous mix; characteristic tripeptide: Gly-Pro-Hyp", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": null, "range": "Not established", "notes": "A mixture of peptides rather than one molecule, so no single half-life applies.", "source": { "type": "qualitative", "note": "a description with no figure; no half-life measurement is cited for it" } }, "fdaStatus": "supplement", "approvalDetails": "Sold as a dietary supplement; Drugs@FDA holds no drug application (openFDA, read September 30, 2026). Supplements are not reviewed for effectiveness before sale.", "mechanism": "Orally ingested collagen peptides are partially digested to dipeptides and tripeptides (primarily Pro-Hyp and Hyp-Gly) that are absorbed intact via PepT1 transporter. These fragments stimulate fibroblast proliferation and collagen/hyaluronic acid synthesis in dermal tissue, and may stimulate chondrocyte activity in cartilage. The Pro-Hyp dipeptide acts as a bioactive signaling molecule, not merely a protein source.", "primaryUses": [ "Skin ageing (randomised trials)", "Bone mineral density in postmenopausal women (randomised trial)", "Activity-related knee pain (randomised trial)", "Muscle mass with resistance training (randomised trial)" ], "typicalDose": { "range": "2.5–15", "unit": "g", "frequency": "daily", "route": "oral", "notes": "The range across the trials here: 2.5 to 5 g for skin, bone and knee outcomes, 10 g for tendon stiffness, 15 g with resistance training." }, "evidenceLevel": "medium", "sources": [ { "type": "fda", "citation": "FDA. Drugs@FDA (openFDA): no drug application for collagen peptides; sold as a dietary supplement. Read September 30, 2026." }, { "type": "pubmed", "citation": "de Miranda RB, et al. \"Effects of hydrolyzed collagen supplementation on skin aging: a systematic review and meta-analysis.\" Int J Dermatol, 2021;60(12):1449-1461. PMID: 33742704.", "pmid": "33742704" }, { "type": "pubmed", "citation": "Proksch E, et al. \"Oral supplementation of specific collagen peptides has beneficial effects on human skin physiology: a double-blind, placebo-controlled study.\" Skin Pharmacol Physiol, 2014;27(1):47-55. PMID: 23949208.", "pmid": "23949208" }, { "type": "pubmed", "citation": "König D, et al. \"Specific Collagen Peptides Improve Bone Mineral Density and Bone Markers in Postmenopausal Women-A Randomized Controlled Study.\" Nutrients, 2018;10(1). PMID: 29337906.", "pmid": "29337906" }, { "type": "pubmed", "citation": "Zdzieblik D, et al. \"Improvement of activity-related knee joint discomfort following supplementation of specific collagen peptides.\" Appl Physiol Nutr Metab, 2017;42(6):588-595. PMID: 28177710.", "pmid": "28177710" }, { "type": "pubmed", "citation": "Zdzieblik D, et al. \"Collagen peptide supplementation in combination with resistance training improves body composition and increases muscle strength in elderly sarcopenic men: a randomised controlled trial.\" Br J Nutr, 2015;114(8):1237-45. PMID: 26353786.", "pmid": "26353786" }, { "type": "pubmed", "citation": "Aussieker T, et al. \"The Effects of Ingesting a Single Bolus of Hydrolyzed Collagen versus Free Amino Acids on Muscle Connective Protein Synthesis Rates.\" Med Sci Sports Exerc, 2025;57(11):2394-2408. PMID: 40523226.", "pmid": "40523226" } ], "interactionCoverage": "none-found", "related": [ "ghk-cu", "matrixyl", "pentapeptide-3", "hyaluronic-acid" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-20", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "A food or supplement ingredient, not a drug; S0 is written for pharmacological substances. Supplements carry a separate risk: contamination with prohibited substances." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "A food or supplement ingredient, not a drug; S0 is written for pharmacological substances. Supplements carry a separate risk: contamination with prohibited substances." } ], "moleculeClass": "blend", "moleculeClassBasis": "hydrolyzed collagen fragments" }, { "id": "colostrinin", "name": "Colostrinin", "aliases": [ "PRP", "Proline-Rich Polypeptide Complex", "CLN" ], "tier": "stub", "category": "cognitive", "subcategory": "immunomodulatory polypeptide complex", "class": "A complex of proline-rich polypeptides isolated from ovine colostrum, studied for immunomodulatory and neuroprotective properties in Alzheimer's disease.", "tagline": "A colostrum-derived polypeptide complex — studied in clinical trials for Alzheimer's disease, with immunomodulatory activity that shifts cytokine profiles from pro- to anti-inflammatory.", "oneLiner": "A mixture of proline-rich polypeptides (PRPs, ~6 kDa) isolated from ovine colostrum, showing Th1/Th2 immunomodulatory activity and neuroprotective effects in early Alzheimer's disease clinical trials.", "sequence": "Complex mixture; dominant peptide contains high proline and N-terminal pyroglutamic acid", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": null, "range": "Unknown", "notes": "Administered orally. Peptide components may be partially digested but biological activity preserved in clinical trials." }, "fdaStatus": "supplement", "approvalDetails": "Available as a dietary supplement (ReGen, various brands). Not FDA-approved as a drug. Small clinical trials in mild Alzheimer's showed modest cognitive stabilization.", "mechanism": "Modulates cytokine production, shifting the balance from pro-inflammatory Th1 toward anti-inflammatory Th2 responses. Inhibits beta-amyloid aggregation in vitro. Reduces oxidative stress via upregulation of antioxidant enzymes. The exact mechanism of cognitive benefit is not established.", "primaryUses": [ "Mild Alzheimer's disease (clinical trials)", "Immune modulation research", "Neuroprotection studies", "Cognitive supplement" ], "typicalDose": { "range": "100", "unit": "mcg", "frequency": "every other day for 3 weeks on, 3 weeks off cycles", "route": "oral (sublingual)", "notes": "Dosing based on clinical trials. Available as tablet or sublingual formulation." }, "evidenceLevel": "low", "sources": [ { "type": "clinical-trial", "citation": "Leszek J, et al. \"Colostrinin: a proline-rich polypeptide (PRP) complex isolated from ovine colostrum for treatment of Alzheimer's disease.\" Arch Immunol Ther Exp, 1999;47:377-385. PMID: 10608295.", "pmid": "10608295" }, { "type": "review", "citation": "Stewart MG. \"Colostrinin: a naturally occurring compound derived from mammalian colostrum with efficacy in treatment of neurodegenerative diseases, including Alzheimer's.\" Expert Opin Pharmacother, 2008;9:2553-2559. PMID: 18778193.", "pmid": "18778193" } ], "interactionCoverage": "none-found", "related": [ "cerebrolysin", "semax", "selank", "davunetide" ], "lastReviewed": "2026-04-20", "publishedAt": "2026-04-20", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "A food or supplement ingredient, not a drug; S0 is written for pharmacological substances. Supplements carry a separate risk: contamination with prohibited substances." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "A food or supplement ingredient, not a drug; S0 is written for pharmacological substances. Supplements carry a separate risk: contamination with prohibited substances." } ], "moleculeClass": "peptide" }, { "id": "corifollitropin-alfa", "name": "Corifollitropin alfa", "aliases": [ "Elonva", "FSH-CTP" ], "tier": "full", "category": "sexual-health", "subcategory": "long-acting recombinant FSH", "class": "Long-acting recombinant FSH — FSH beta-subunit fused to the C-terminal peptide (CTP) of hCG-beta, producing a glycoprotein with extended serum half-life enabling a single weekly injection to replace 7 days of daily FSH.", "tagline": "Elonva — recombinant FSH fused to the C-terminal peptide of hCG (about 65-hour half-life), given as one injection to replace the first week of daily FSH in IVF cycles. Authorised in the EU since January 2010; never approved in the US.", "oneLiner": "A long-acting recombinant FSH produced by fusing the C-terminal peptide (CTP) of hCG-beta onto the FSH beta-subunit in a CHO-cell expression system, exploiting the same prolonged-half-life strategy Schering-Plough/Merck used for hCG. A single 100 or 150 mcg SC injection initiates and sustains multifollicular development for the first 7 days of a controlled-ovarian-stimulation cycle. EMA-approved as Elonva in January 2010. Never FDA-approved: Merck submitted but received a Complete Response Letter from the FDA in 2010 and has not re-filed; the product remains commercially available in Europe and many other markets, but is not available in the United States.", "sequence": null, "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": 65, "unit": "hours", "range": "about 65 hours (plasma)", "notes": "The hybrid β-subunit carrying hCG's C-terminal peptide slows absorption and elimination (Int J Womens Health 2011 review); the earlier dataset figure of 69 hours had no source." }, "fdaStatus": "not-approved-us", "approvalDetails": "EU: authorised centrally as Elonva on January 25, 2010 (EMA register, read September 30, 2026), as a multifollicular stimulant for controlled ovarian stimulation with a GnRH antagonist in assisted reproduction. US: Drugs@FDA holds no application (read September 30, 2026). Developed by Schering-Plough.", "mechanism": "FSHR agonism identical to other FSH products; the CTP fusion provides prolonged half-life through CTP-associated O-linked glycan sialylation that reduces renal clearance — the same mechanism that gives hCG its longer half-life relative to LH. Pharmacologic effect of a single 100 mcg dose approximates 7 daily 150 IU doses of conventional FSH.", "primaryUses": [ "Controlled ovarian stimulation for IVF/ICSI in combination with a GnRH antagonist (ex-US)" ], "typicalDose": { "range": "100 (<60 kg) or 150 (≥60 kg)", "unit": "mcg", "frequency": "single SC injection on stimulation day 1", "route": "subcutaneous", "notes": "Single dose initiates and maintains multifollicular development for 7 days. From day 8 onward, conventional daily recombinant FSH is added if additional stimulation is needed. GnRH antagonist (ganirelix or cetrorelix) started on day 5–6 per local protocol." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Boostanfar R, et al. \"Large, comparative, randomized double-blind trial confirming noninferiority of pregnancy rates for corifollitropin alfa compared with recombinant follicle-stimulating hormone in a gonadotropin-releasing hormone antagonist controlled ovarian stimulation protocol in older patients undergoing in vitro fertilization.\" Fertil Steril, 2015;104(1):94-103.e1. PMID: 26003273.", "pmid": "26003273" }, { "type": "pubmed", "citation": " \"Corifollitropin alfa for ovarian stimulation in IVF: a randomized trial in lower-body-weight women.\" Reprod Biomed Online, 2010;21(1):66-76. PMID: 20483664.", "pmid": "20483664" }, { "type": "pubmed", "citation": "Fauser BC, et al. \"Pharmacokinetics and follicular dynamics of corifollitropin alfa versus recombinant FSH during ovarian stimulation for IVF.\" Reprod Biomed Online, 2010;21(5):593-601. PMID: 20843746.", "pmid": "20843746" }, { "type": "pubmed", "citation": "Tarlatzis BC, et al. \"Comparative incidence of ovarian hyperstimulation syndrome following ovarian stimulation with corifollitropin alfa or recombinant FSH.\" Reprod Biomed Online, 2012;24(4):410-9. PMID: 22386594.", "pmid": "22386594" }, { "type": "pubmed", "citation": "Bonduelle M, et al. \"Prospective follow-up of 838 fetuses conceived after ovarian stimulation with corifollitropin alfa: comparative and overall neonatal outcome.\" Hum Reprod, 2012;27(7):2177-85. PMID: 22587997.", "pmid": "22587997" }, { "type": "pubmed", "citation": "de Kam PJ, et al. \"Single therapeutic and supratherapeutic doses of corifollitropin alfa, a sustained follicle stimulant, do not prolong the QTcF-interval in healthy postmenopausal volunteers.\" Int J Clin Pharmacol Ther, 2015;53(9):772-82. PMID: 26227099.", "pmid": "26227099" }, { "type": "pubmed", "citation": "Cozzolino M, et al. \"Corifollitropin alfa for ovarian stimulation in in vitro fertilization: a systematic review and meta-analysis of randomized controlled trials.\" Fertil Steril, 2019;111(4):722-733. PMID: 30929731.", "pmid": "30929731" }, { "type": "pubmed", "citation": "Croxtall JD, et al. \"Corifollitropin alfa: a review of its use in controlled ovarian stimulation for assisted reproduction.\" BioDrugs, 2011;25(4):243-54. PMID: 21815699.", "pmid": "21815699" }, { "type": "pubmed", "citation": "Seyhan A, et al. \"The role of corifollitropin alfa in controlled ovarian stimulation for IVF in combination with GnRH antagonist.\" Int J Womens Health, 2011;3:243-55. PMID: 21892335.", "pmid": "21892335" }, { "type": "pubmed", "citation": "Loutradis D, et al. \"Corifollitropin alfa, a long-acting follicle-stimulating hormone agonist for the treatment of infertility.\" Curr Opin Investig Drugs, 2009;10(4):372-80. PMID: 19337959.", "pmid": "19337959" }, { "type": "other", "citation": "European Medicines Agency. Medicines register: Elonva (corifollitropin alfa), authorised; marketing authorisation date January 25, 2010. Read September 30, 2026." }, { "type": "fda", "citation": "FDA. Drugs@FDA (openFDA): no application for corifollitropin alfa. Read September 30, 2026." }, { "type": "other", "citation": "European Medicines Agency. Elonva (corifollitropin alfa): EPAR product information, Summary of Product Characteristics section 4.2 (read September 30, 2026)." } ], "interactionCoverage": "none-found", "related": [ "follitropin-alfa", "follitropin-beta", "follitropin-delta", "ganirelix", "cetrorelix" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": "EU (EMA), UK, Canada, Australia", "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Follicle-stimulating hormone is not named, and S2.2.1's examples (CG, LH, GnRH agonists, kisspeptin) are testosterone-stimulating hormones, which FSH is not." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Follicle-stimulating hormone is not named, and S2.2.1's examples (CG, LH, GnRH agonists, kisspeptin) are testosterone-stimulating hormones, which FSH is not." } ], "moleculeClass": "protein", "moleculeClassBasis": "recombinant FSH" }, { "id": "cortagen", "name": "Cortagen", "aliases": [ "Cortexin peptide", "Ala-Glu-Asp-Pro", "AEDP" ], "tier": "stub", "category": "longevity", "subcategory": "Khavinson short-chain bioregulator (cerebral cortex)", "class": "A synthetic short tetrapeptide derived from bovine cerebral cortex extract (Cortexin), developed by the Khavinson group as a \"cerebral bioregulator\".", "tagline": "A Khavinson-group tetrapeptide isolated from cortex tissue — used in Russian neurology practice for post-stroke cognitive deficit; evidence is almost entirely Russian-language with minimal Western replication.", "oneLiner": "One of the Khavinson short-chain peptide bioregulators (Ala-Glu-Asp-Pro), derived from the parent Cortexin extract and proposed to regulate gene expression in cortical neurons and support recovery after ischemic brain injury in the Russian clinical literature.", "sequence": "Ala-Glu-Asp-Pro", "molecularFormula": "C16H24N4O8", "molecularWeight": 400.39, "halfLife": { "value": null, "unit": null, "range": "undetermined", "notes": "Systemic pharmacokinetics of short Khavinson peptides have not been characterized in Western-standard studies." }, "fdaStatus": "research-only", "approvalDetails": "Not FDA-approved. The parent Cortexin extract is registered as a medicine in Russia and several CIS countries for neurological indications; the synthetic Cortagen short peptide is marketed as a bioregulator / supplement in the same jurisdictions.", "mechanism": "Hypothesized by the Khavinson group to act as a tissue-specific gene-expression modulator — the short peptide sequence is proposed to bind DNA promoter regions in cortical cells and regulate transcription of neurotrophic and neuroprotective genes. Western mechanistic studies are limited; most published work is from the St. Petersburg Institute of Bioregulation and Gerontology.", "primaryUses": [ "Research into post-ischemic cognitive recovery (Russian clinical literature)", "Investigational neuroprotection" ], "typicalDose": { "range": "not established", "unit": null, "frequency": "not established", "route": "intramuscular (parent Cortexin)", "notes": "Russian clinical practice uses the parent Cortexin extract at 10 mg IM for 10 days; dosing for the synthetic short peptide is not standardized outside Khavinson-group studies." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Khavinson VK. \"Peptides and ageing.\" Neuro Endocrinol Lett, 2002;23 Suppl 3:11-144. PMID: 12374906.", "pmid": "12374906" }, { "type": "review", "citation": "Khavinson VK, Malinin VV. \"Gerontological aspects of genome peptide regulation.\" Karger AG, Basel, 2005." } ], "interactionCoverage": "unreviewed", "related": [ "epithalon", "cerebrolysin", "pinealon" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "cortexin", "name": "Cortexin", "aliases": [ "Cortexinum", "Cortical polypeptide complex" ], "tier": "stub", "category": "cognitive", "subcategory": "Bovine cortex-derived polypeptide complex", "class": "A mixture of low-molecular-weight polypeptides (<10 kDa) extracted from the cerebral cortex of young calves or pigs, marketed primarily in Russia and the CIS as a nootropic and neuroprotective agent.", "tagline": "A Russian polypeptide bioregulator (Geropharm / Герофарм) extracted from bovine or porcine cerebral cortex, approved in Russia for a broad array of neurological indications including cerebrovascular disease, traumatic brain injury, epilepsy, and cognitive impairment. Not FDA- or EMA-approved; clinical evidence base is almost entirely Russian-language and of low-to-moderate methodological rigor by Western standards.", "oneLiner": "A complex mixture of water-soluble polypeptides with molecular weight below 10 kDa, extracted from the cerebral cortex of young cattle or pigs. Developed at the Russian Military Medical Academy in the 1980s and now produced primarily by Geropharm (Saint Petersburg). Marketed in Russia, Belarus, Ukraine, Kazakhstan, and several CIS states as a neurotropic agent for cerebrovascular disease, traumatic brain injury, post-stroke recovery, pediatric cognitive delay, and epilepsy. Mechanism is proposed as pleiotropic neurotrophic support via the mixture's aggregate small peptides and amino acids. Not approved in the US or EU.", "sequence": "Polypeptide mixture — not a single-sequence molecule", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": null, "range": "Not characterized", "notes": "Individual peptide components have not been individually pharmacokinetically profiled; the product is characterized as a lyophilizate with standardized polypeptide content but without single-molecule PK." }, "fdaStatus": "not-approved-us", "approvalDetails": "Approved in Russia and in several CIS member states (Belarus, Ukraine, Kazakhstan, etc.) as a prescription medicine for a wide range of neurological indications in adults and children. Manufactured principally by Geropharm. Not approved by the FDA, EMA, MHRA, PMDA, Health Canada, or the TGA. Not available through any regulated Western pharmaceutical distribution channel.", "mechanism": "Proposed neurotrophic and neuromodulatory effects of the low-molecular-weight peptide fraction, including putative GABAergic modulation, antioxidant effects, and support of synaptic plasticity. Mechanism is poorly characterized at the molecular level; most published mechanistic work is from Russian research institutions and has not been widely independently replicated. The heterogeneity of the preparation (a polypeptide mixture rather than a defined single molecule) complicates regulatory assessment by Western agencies accustomed to single-entity molecules.", "primaryUses": [ "Cerebrovascular disease (Russian approval)", "Traumatic brain injury rehabilitation (Russian approval)", "Post-stroke cognitive recovery (Russian approval)", "Pediatric cerebral palsy and developmental delay (Russian approval)", "Epilepsy as adjunct (Russian approval)" ], "typicalDose": { "range": "10 (adults); 0.5 mg/kg (pediatrics)", "unit": "mg", "frequency": "once daily for 10 days", "route": "intramuscular", "notes": "Standard Russian dosing: 10 mg IM once daily for 10 days in adults, or 0.5 mg/kg in children <20 kg, reconstituted in 1–2 mL of sterile water or saline. Repeat courses every 3–6 months as clinically indicated." }, "evidenceLevel": "low", "sources": [ { "type": "other", "citation": "Cortexin (Cortexinum) Russian Summary of Product Characteristics. Geropharm JSC, Saint Petersburg, Russia." }, { "type": "pubmed", "citation": "Skoromets AA, et al. \"Review of clinical studies of Cortexin in cerebrovascular disease and traumatic brain injury.\" Zh Nevrol Psikhiatr Im S S Korsakova, 2013;113:63-68 (Russian)." }, { "type": "review", "citation": "Granstrem O, et al. \"Cortexin — a novel therapeutic agent for epilepsy, cerebrovascular and traumatic CNS disorders.\" Int J Biomed, 2013;3:208-213." } ], "interactionCoverage": "none-found", "related": [ "cerebrolysin", "semax", "selank" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": "Russia and several CIS states", "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "blend", "moleculeClassBasis": "mixture of low-molecular-weight polypeptides" }, { "id": "corticorelin", "name": "Corticorelin", "aliases": [ "Acthrel", "human CRH", "ovine CRH", "corticorelin ovine triflutate", "CRF" ], "tier": "mid", "category": "growth-hormone", "subcategory": "CRH / CRF diagnostic peptide", "class": "Synthetic corticotropin-releasing hormone (CRH, 41 amino acids) — ovine sequence marketed in the US as Acthrel for diagnostic evaluation of Cushing syndrome.", "tagline": "Ferring Pharmaceuticals' synthetic ovine CRH (Acthrel) — FDA-approved diagnostic peptide used to distinguish pituitary Cushing disease from ectopic ACTH secretion via inferior petrosal sinus sampling or peripheral ACTH/cortisol response testing.", "oneLiner": "Synthetic corticotropin-releasing hormone (CRH, also called corticotropin-releasing factor, CRF) — a 41-amino-acid hypothalamic releasing peptide. The ovine sequence is marketed in the United States as Acthrel (Ferring Pharmaceuticals) as a diagnostic agent to evaluate the pituitary-adrenal axis. Principal clinical use is distinguishing pituitary Cushing disease from ectopic ACTH secretion during inferior petrosal sinus sampling (IPSS) or during peripheral ACTH/cortisol response testing — pituitary adenomas respond to CRH with a brisk ACTH rise, while ectopic ACTH-secreting tumors typically do not.", "sequence": "SQEPPISLDLTFHLLREVLEMTKADQLAQQAHSNRKLLDIA (ovine CRH, 41 aa)", "molecularFormula": null, "molecularWeight": 4670, "halfLife": { "value": 73, "unit": "minutes", "range": "11.6 minutes (fast component) and 73 minutes (slow component)", "notes": "Single intravenous diagnostic dose; no half-life is stated in the sources on this page.", "source": { "type": "label", "ref": "Acthrel prescribing information, section 12.3 (DailyMed version 26, effective November 12, 2021; read September 30, 2026)" } }, "fdaStatus": "approved", "approvalDetails": "FDA: ACTHREL (corticorelin ovine triflutate for injection), BLA 020162 (Ferring), approved May 23, 1996 (Drugs@FDA), for differentiating pituitary and ectopic ACTH production in ACTH-dependent Cushing's syndrome; label version of November 12, 2021.", "mechanism": "Binds corticotropin-releasing hormone receptor type 1 (CRHR1) on anterior pituitary corticotrophs, stimulating ACTH release and, downstream, cortisol secretion. In Cushing diagnostics, a robust ACTH response indicates intact pituitary corticotroph tissue (characteristic of pituitary microadenoma), while blunted or absent response during IPSS with peripheral ACTH rise suggests an ectopic ACTH source.", "primaryUses": [ "Diagnostic: differential diagnosis of Cushing syndrome (pituitary vs ectopic ACTH)" ], "typicalDose": { "range": "1", "unit": "mcg/kg", "frequency": "single diagnostic dose", "route": "intravenous bolus", "notes": "Administered during inferior petrosal sinus sampling or as part of a peripheral CRH stimulation test. Central-to-peripheral ACTH gradient interpretation follows standard endocrinology protocols." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Ferring. ACTHREL (corticorelin ovine triflutate for injection), US prescribing information: indication, contraindication (hypersensitivity to ovine corticorelin), dose-dependent adverse effects. DailyMed version of November 12, 2021; read September 30, 2026." }, { "type": "pubmed", "citation": "Elenius H, et al. \"Ovine CRH Stimulation and 8 mg Dexamethasone Suppression Tests in 323 Patients With ACTH-Dependent Cushing's Syndrome.\" J Clin Endocrinol Metab, 2023;109(1):e182-e189. PMID: 37531629.", "pmid": "37531629" }, { "type": "pubmed", "citation": "Detomas M, et al. \"Outcome of CRH stimulation test and overnight 8 mg dexamethasone suppression test in 469 patients with ACTH-dependent Cushing's syndrome.\" Front Endocrinol (Lausanne), 2022;13:955945. PMID: 36277711.", "pmid": "36277711" }, { "type": "pubmed", "citation": "Natt N, et al. \"The ovine corticotropin-releasing hormone stimulation test in the differential diagnosis of adrenocorticotropic hormone-dependent cushing's syndrome.\" Endocr Pract, 1997;3(3):130-4. PMID: 15251472.", "pmid": "15251472" }, { "type": "pubmed", "citation": "Boyle J, et al. \"CRH stimulation improves (18)F-FDG-PET detection of pituitary adenomas in Cushing's disease.\" Endocrine, 2019;65(1):155-165. PMID: 31062234.", "pmid": "31062234" }, { "type": "fda", "citation": "FDA. Drugs@FDA (openFDA): ACTHREL, BLA 020162, approved May 23, 1996. Read September 30, 2026." } ], "interactionCoverage": "label", "related": [ "somatropin", "sermorelin", "protirelin", "gonadorelin" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.2.2", "named": true, "wording": "corticorelin", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.2.2", "named": true, "wording": "corticorelin", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "cotadutide", "name": "Cotadutide", "aliases": [ "MEDI0382" ], "tier": "mid", "category": "pipeline", "subcategory": "GLP-1 / glucagon dual agonist (discontinued)", "class": "A dual agonist peptide targeting the GLP-1 and glucagon receptors, developed by MedImmune / AstraZeneca and discontinued in 2023.", "tagline": "A GLP-1 and glucagon dual agonist that reached phase 2b in diabetes, kidney and liver disease before AstraZeneca stopped it in 2023.", "oneLiner": "A once-daily peptide that activates the GLP-1 and glucagon receptors together, lowering glucose and weight while acting on the liver.", "sequence": null, "molecularFormula": "C167H252N42O55", "molecularWeight": 3728.0, "halfLife": { "value": 11, "unit": "hours", "range": "9.5 to 12.1 hours", "source": { "type": "pmid", "pmid": "29926478", "cite": "Ambery PD, et al. \"MEDI0382, a GLP-1/glucagon receptor dual agonist, meets safety and tolerability endpoints in a single-dose, healthy-subject, randomized, Phase 1 study.\" Br J Clin Pharmacol, 2018;84(10):2325-2335. PMID: 29926478." } }, "fdaStatus": "discontinued", "approvalDetails": "Not approved anywhere. AstraZeneca's first-quarter 2023 results announcement records the discontinuation of the daily formulation in NASH for portfolio prioritisation; no phase 3 was completed.", "mechanism": "Balanced agonism at the GLP-1 and glucagon receptors in a single peptide. GLP-1 agonism drives the canonical appetite-suppression, delayed-gastric-emptying, and glucose-dependent insulin secretion. Glucagon receptor co-agonism adds an energy-expenditure component — increased hepatic fatty acid oxidation, reduced hepatic steatosis, and modest thermogenic effects — while the GLP-1 arm counteracts the glucagon-driven tendency toward hyperglycemia. The same dual-agonist logic underlies pemvidutide and survodutide.", "primaryUses": [ "Type 2 diabetes with chronic kidney disease (phase 2b)", "MASH with fibrosis (phase 2)", "Type 2 diabetes and weight (phase 2b)" ], "typicalDose": { "range": "100–600", "unit": "mcg", "frequency": "once daily", "route": "subcutaneous", "notes": "Phase 2 protocols titrated from 100 mcg to 300–600 mcg once daily." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "Ambery PD, et al. \"MEDI0382, a GLP-1/glucagon receptor dual agonist, meets safety and tolerability endpoints in a single-dose, healthy-subject, randomized, Phase 1 study.\" Br J Clin Pharmacol, 2018;84(10):2325-2335. PMID: 29926478.", "pmid": "29926478" }, { "type": "pubmed", "citation": "Ambery P, et al. \"MEDI0382, a GLP-1 and glucagon receptor dual agonist, in obese or overweight patients with type 2 diabetes: a randomised, controlled, double-blind, ascending dose and phase 2a study.\" Lancet, 2018;391(10140):2607-2618. PMID: 29945727.", "pmid": "29945727" }, { "type": "pubmed", "citation": "Nahra R, et al. \"Effects of Cotadutide on Metabolic and Hepatic Parameters in Adults With Overweight or Obesity and Type 2 Diabetes: A 54-Week Randomized Phase 2b Study.\" Diabetes Care, 2021;44(6):1433-1442. PMID: 34016612.", "pmid": "34016612" }, { "type": "pubmed", "citation": "Selvarajah V, et al. \"A randomized phase 2b trial examined the effects of the glucagon-like peptide-1 and glucagon receptor agonist cotadutide on kidney outcomes in patients with diabetic kidney disease.\" Kidney Int, 2024;106(6):1170-1180. PMID: 39218393.", "pmid": "39218393" }, { "type": "pubmed", "citation": "Shankar SS, et al. \"Safety and Efficacy of Novel Incretin Co-agonist Cotadutide in Biopsy-proven Noncirrhotic MASH With Fibrosis.\" Clin Gastroenterol Hepatol, 2024;22(9):1847-1857.e11. PMID: 38729399.", "pmid": "38729399" }, { "type": "other", "citation": "AstraZeneca PLC. Q1 2023 results announcement: the Phase II/III NASH trial discontinued for portfolio prioritisation (SEC Form 6-K, read September 30, 2026)." }, { "type": "pubmed", "citation": "Boland ML, et al. \"Resolution of NASH and hepatic fibrosis by the GLP-1R/GcgR dual-agonist Cotadutide via modulating mitochondrial function and lipogenesis.\" Nat Metab, 2020;2(5):413-431. PMID: 32478287.", "pmid": "32478287" } ], "interactionCoverage": "none-found", "related": [ "pemvidutide", "survodutide", "retatrutide" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "A discontinued drug: S0's own examples include discontinued drugs." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "A discontinued drug: S0's own examples include discontinued drugs." } ], "moleculeClass": "peptide" }, { "id": "danuglipron", "name": "Danuglipron", "aliases": [ "PF-06882961" ], "tier": "stub", "category": "pipeline", "subcategory": "oral small-molecule GLP-1 receptor agonist (discontinued)", "class": "An orally bioavailable small-molecule GLP-1 receptor agonist.", "tagline": "⚠ Not a peptide — small molecule. Pfizer's discontinued oral GLP-1 program — halted April 14, 2025 after a single case of potential drug-induced liver injury in a once-daily dose-optimization study, ending Pfizer's second oral GLP-1 failure in as many years. Included in this peptide encyclopedia because the audience frequently searches for it alongside peptide GLP-1 agonists.", "oneLiner": "A small-molecule non-peptide GLP-1 receptor agonist developed by Pfizer as a once-daily oral tablet for chronic weight management, discontinued on April 14, 2025 after a single asymptomatic participant in a dose-optimization study experienced potential drug-induced liver injury that resolved on drug withdrawal — Pfizer's second oral GLP-1 program to fail since 2023.", "sequence": null, "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": "hours", "range": "short; required BID or once-daily formulation work", "notes": "Twice-daily formulation was abandoned in late 2023 for tolerability; once-daily formulation work was underway when the program was discontinued in April 2025." }, "fdaStatus": "discontinued", "approvalDetails": "Discontinued by Pfizer on April 14, 2025. Prior Phase 2b trial in adults with obesity (NCT04707313) had shown meaningful weight reductions — placebo-adjusted weight loss of approximately 8–13% at 32 weeks — but over half of participants discontinued treatment due to nausea (73%), vomiting (47%), and diarrhea (25%). Once-daily dose-optimization studies (NCT06567327, NCT06568731) met pharmacokinetic objectives but the single liver-injury case, combined with regulatory feedback, ended the program.", "mechanism": "Binds the transmembrane region of the GLP-1 receptor as a small-molecule agonist, distinct from the orthosteric peptide-binding pocket occupied by semaglutide and other peptide GLP-1 agonists. This unusual binding mode was what allowed the oral, non-peptide format — and also what made the pharmacology subtly different from peptide GLP-1s.", "primaryUses": [ "Historical: oral chronic weight management (discontinued)", "No current clinical or community use" ], "typicalDose": { "range": "discontinued", "unit": "", "frequency": "historical: once daily (final) or twice daily (earlier)", "route": "oral", "notes": "Development halted before final dose was established." }, "evidenceLevel": "medium", "sources": [ { "type": "news-release", "citation": "Pfizer Inc. \"Pfizer Provides Update on Oral GLP-1 Receptor Agonist Danuglipron.\" Press release, April 14, 2025." }, { "type": "clinicaltrials", "citation": "NCT04707313 — Phase 2b danuglipron in obesity. ClinicalTrials.gov." }, { "type": "clinicaltrials", "citation": "NCT06567327, NCT06568731 — once-daily danuglipron dose-optimization studies. ClinicalTrials.gov." } ], "interactionCoverage": "none-found", "related": [ "semaglutide", "liraglutide", "orforglipron" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "A discontinued drug: S0's own examples include discontinued drugs." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "A discontinued drug: S0's own examples include discontinued drugs." } ], "moleculeClass": "small-molecule", "moleculeClassBasis": "small-molecule" }, { "id": "daptomycin", "name": "Daptomycin", "aliases": [ "Cubicin", "LY146032" ], "tier": "mid", "category": "immune", "subcategory": "lipopeptide antibiotic", "class": "A cyclic lipopeptide antibiotic derived from Streptomyces roseosporus, with a unique calcium-dependent mechanism of bacterial membrane disruption.", "tagline": "A last-resort lipopeptide antibiotic — the first-in-class cyclic peptide that kills MRSA and VRE by depolarizing bacterial membranes, without resistance through traditional mechanisms.", "oneLiner": "A 13-amino-acid cyclic lipopeptide antibiotic with a decanoyl fatty acid tail, FDA-approved for complicated skin infections and S. aureus bacteremia, acting by calcium-dependent insertion into bacterial cell membranes causing rapid depolarization.", "sequence": "Cyclic 13-amino-acid core with decanoyl lipid tail", "molecularFormula": "C72H101N17O26", "molecularWeight": 1620.7, "halfLife": { "value": 8, "unit": "hours", "range": "7.9 to 8.3 hours in healthy adults across 4 to 8 mg/kg", "source": { "type": "label", "ref": "Cubicin RF (daptomycin) prescribing information, sections 1, 2, 5, 6 and 12.3 (DailyMed SPL version 22, effective March 17, 2025; read October 1, 2026)" } }, "fdaStatus": "approved", "approvalDetails": "Cubicin, NDA 021572, approved September 12, 2003, with Cubicin RF under the same application; generic daptomycin approved from 2021 (Drugs@FDA, read October 1, 2026). Indicated for complicated skin and skin-structure infections and S. aureus bloodstream infections; the label rules out pneumonia and left-sided endocarditis.", "mechanism": "In the presence of calcium ions, daptomycin oligomerizes and inserts into the gram-positive bacterial cell membrane, forming ion-conducting channels that cause rapid depolarization. Loss of membrane potential halts DNA, RNA, and protein synthesis simultaneously, producing rapid bactericidal activity. The mechanism is distinct from all other antibiotic classes.", "primaryUses": [ "MRSA skin and soft tissue infections", "S. aureus bacteremia", "Right-sided endocarditis", "Vancomycin-resistant Enterococcus (VRE) infections (off-label)" ], "typicalDose": { "range": "4-6", "unit": "mg/kg", "frequency": "once every 24 hours", "route": "intravenous", "notes": "Cubicin RF label: 4 mg/kg for complicated skin infections for 7 to 14 days, 6 mg/kg for S. aureus bacteremia for 2 to 6 weeks, each every 48 hours instead below a creatinine clearance of 30 mL/min." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Cubicin RF (daptomycin) prescribing information, sections 1, 2, 5, 6 and 12.3 (DailyMed SPL version 22, effective March 17, 2025; read October 1, 2026)." }, { "type": "pubmed", "citation": "Fowler VG Jr, et al. \"Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus.\" N Engl J Med, 2006;355(7):653-65. PMID: 16914701.", "pmid": "16914701" }, { "type": "pubmed", "citation": "Tong SYC, et al. \"Effect of Vancomycin or Daptomycin With vs Without an Antistaphylococcal β-Lactam on Mortality, Bacteremia, Relapse, or Treatment Failure in Patients With MRSA Bacteremia: A Randomized Clinical Trial.\" JAMA, 2020;323(6):527-537. PMID: 32044943.", "pmid": "32044943" }, { "type": "pubmed", "citation": "Pujol M, et al. \"Daptomycin Plus Fosfomycin Versus Daptomycin Alone for Methicillin-resistant Staphylococcus aureus Bacteremia and Endocarditis: A Randomized Clinical Trial.\" Clin Infect Dis, 2021;72(9):1517-1525. PMID: 32725216.", "pmid": "32725216" }, { "type": "pubmed", "citation": "Bradley J, et al. \"Daptomycin for Complicated Skin Infections: A Randomized Trial.\" Pediatrics, 2017;139(3). PMID: 28202770.", "pmid": "28202770" }, { "type": "pubmed", "citation": "Dvorchik B, et al. \"Population pharmacokinetics of daptomycin.\" Antimicrob Agents Chemother, 2004;48(8):2799-807. PMID: 15273084.", "pmid": "15273084" } ], "interactionCoverage": "label", "related": [ "ll-37", "pexiganan", "omiganan" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-20", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "davunetide", "name": "Davunetide", "aliases": [ "NAP", "AL-108", "AL-208", "NAPVSIPQ" ], "tier": "mid", "category": "cognitive", "subcategory": "ADNP-derived microtubule-stabilizing peptide", "class": "An eight-amino-acid peptide fragment of activity-dependent neuroprotective protein (ADNP) investigated as a microtubule-stabilizing neuroprotective agent in tauopathies and schizophrenia.", "tagline": "NAPVSIPQ, the minimum active fragment of ADNP — an 8-amino-acid neuroprotective peptide studied in Phase 2 (cognition in mild cognitive impairment, schizophrenia) and Phase 3 (progressive supranuclear palsy). The Phase 3 PSP trial failed in 2012; development continues in schizophrenia (Coronis / ATL-104) and ADNP syndrome research.", "oneLiner": "An octapeptide (Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln) corresponding to the minimal neuroprotective fragment of activity-dependent neuroprotective protein (ADNP), discovered by Illana Gozes at Tel Aviv University. Originally advanced intranasally by Allon Therapeutics through a Phase 2b program in amnestic mild cognitive impairment and a Phase 3 program (GN-1058) in progressive supranuclear palsy (PSP) — the Phase 3 PSP trial failed its primary endpoints in late 2012, ending Allon. Assets subsequently licensed to Paladin Labs and more recently Coronis Neurosciences for continued development in schizophrenia and ADNP-syndrome (Helsmoortel-Van der Aa syndrome) indications.", "sequence": "Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln", "molecularFormula": "C36H60N10O12", "molecularWeight": 824.9, "halfLife": { "value": null, "unit": null, "range": "not established in published human studies", "notes": "No human half-life is reported in the trials cited; formula and weight are PubChem's for NAPVSIPQ (the earlier dataset formula did not match the sequence).", "source": { "type": "qualitative", "note": "a description with no figure; no half-life measurement is cited for it" } }, "fdaStatus": "clinical-trials", "approvalDetails": "Not FDA-approved. Allon Therapeutics advanced davunetide through Phase 2 in amnestic mild cognitive impairment (2008, met multiple secondary cognition endpoints but not primary) and Phase 3 in progressive supranuclear palsy (GN-1058, 2010–2012; n=313; did not meet co-primary endpoints for PSPRS or SEADL). Allon ceased independent operations after the PSP readout. Davunetide (as ATL-104 / Coronis asset) was reported in 2022–2024 to be under evaluation for cognitive and negative symptoms of schizophrenia, and has been the subject of continued preclinical interest as a candidate for ADNP syndrome.", "mechanism": "The parent protein ADNP binds microtubules via its SxIP motif (Ser-Ile-Pro — residues 5–7 of NAP) and interacts with end-binding proteins EB1/EB3 to stabilize dynamic microtubule plus-ends. NAP inherits this microtubule-stabilizing activity and has been reported to reduce tau hyperphosphorylation, protect against amyloid-β toxicity in vitro and in vivo, and normalize axonal transport deficits in tauopathy models. Mechanism of action is well characterized preclinically and represents a distinct therapeutic rationale from amyloid- or tau-clearance strategies.", "primaryUses": [ "Progressive supranuclear palsy (failed Phase 3, 2012)", "Amnestic mild cognitive impairment (Phase 2 completed)", "Schizophrenia — negative symptoms and cognition (investigational, ATL-104 / Coronis)", "ADNP syndrome / Helsmoortel-Van der Aa syndrome (preclinical and translational research)" ], "typicalDose": { "range": "15–30 (nasal)", "unit": "mg", "frequency": "twice daily", "route": "intranasal", "notes": "Phase 2 and Phase 3 trial dosing used intranasal davunetide 15 mg twice daily or 30 mg twice daily. No established dose for any approved indication." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "Morimoto BH, et al. \"A double-blind, placebo-controlled, ascending-dose, randomized study to evaluate the safety, tolerability and effects on cognition of AL-108 after 12 weeks of intranasal administration in subjects with mild cognitive impairment.\" Dement Geriatr Cogn Disord, 2013;35(5-6):325-36. PMID: 23594991.", "pmid": "23594991" }, { "type": "pubmed", "citation": "Javitt DC, et al. \"Effect of the neuroprotective peptide davunetide (AL-108) on cognition and functional capacity in schizophrenia.\" Schizophr Res, 2012;136(1-3):25-31. PMID: 22169248.", "pmid": "22169248" }, { "type": "pubmed", "citation": "Boxer AL, et al. \"Davunetide in patients with progressive supranuclear palsy: a randomised, double-blind, placebo-controlled phase 2/3 trial.\" Lancet Neurol, 2014;13(7):676-85. PMID: 24873720.", "pmid": "24873720" }, { "type": "pubmed", "citation": "Gozes I, et al. \"Davunetide sex-dependently boosts memory in prodromal Alzheimer's disease.\" Transl Psychiatry, 2024;14(1):412. PMID: 39358355.", "pmid": "39358355" }, { "type": "other", "citation": "PubChem. Davunetide (CID 9832404): molecular formula C36H60N10O12, molecular weight 824.9. Read September 30, 2026." } ], "interactionCoverage": "none-found", "related": [ "cerebrolysin", "p21", "semax" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." } ], "moleculeClass": "peptide" }, { "id": "decorinyl", "name": "Decorinyl", "aliases": [ "Tripeptide-10 Citrulline", "T10-C", "Lys-Asp-Ile-Cit-NH2", "Decorin-mimetic peptide" ], "tier": "stub", "category": "cosmetic", "subcategory": "topical cosmetic peptide (decorin mimetic)", "class": "A synthetic tetrapeptide (three proteinogenic residues plus a C-terminal citrulline) modeled on the collagen-binding motif of decorin, formulated as a topical cosmetic ingredient to regulate collagen fibrillogenesis and fibril diameter.", "tagline": "The actual identity of the Lipotec \"Decorinyl®\" ingredient — a decorin-mimetic tetrapeptide (Lys-Asp-Ile-Cit-NH2) engineered to regulate collagen fibril diameter and uniformity in aged skin. Often confused with \"Tridecapeptide-4\"; the authoritative literature (Puig et al. 2008) classifies it as INCI Tripeptide-10 Citrulline.", "oneLiner": "A synthetic tetrapeptide modeled on the collagen-binding motif of decorin, a small leucine-rich proteoglycan (SLRP) that controls fibril diameter and regular spacing of type I collagen in the dermis. The INCI designation \"Tripeptide-10 Citrulline\" reflects three proteinogenic residues (Lys-Asp-Ile) plus a C-terminal L-citrulline; the charge pattern (+/−/0/+) reproduces the decorin motif that binds collagen fibrils. Developed by Lipotec (acquired by Lubrizol in 2012) and commercialised as Decorinyl®. A 43-subject placebo-controlled trial of a 0.01% liposomal formulation (Puig et al. 2008) reported a 54% increase in skin suppleness at 28 days; additional in-vitro evidence shows thinner, more uniform collagen fibrils. Cosmetic ingredient only; not a drug.", "sequence": "Lys-Asp-Ile-Cit-NH2", "molecularFormula": "C22H42N8O7", "molecularWeight": 530.62, "halfLife": { "value": null, "unit": null, "range": "topical only", "notes": "Systemic absorption from topical cosmetic formulations is minimal." }, "fdaStatus": "research-only", "approvalDetails": "Cosmetic ingredient; not a drug. Registered under INCI name Tripeptide-10 Citrulline.", "mechanism": "Mimics the collagen-binding region of decorin, a small leucine-rich proteoglycan (SLRP) that regulates type I collagen fibrillogenesis by binding periodically to the surface of fibrils and limiting lateral fusion. The four-residue Lys-Asp-Ile-Cit motif preserves the +/−/0/+ charge pattern of the native decorin binding sequence, enabling it to occupy the same fibril surface site. In aged skin, endogenous decorin is progressively truncated and loses its collagen-regulating C-terminal region, producing thicker and irregular fibrils; Tripeptide-10 Citrulline is proposed to partially compensate for this truncation. Ex-vivo skin equivalents and in-vitro fibrillogenesis assays show narrower, more uniform fibrils in treated samples. Commonly co-formulated with Tripeptide-1 (in Trylagen™) or Acetyl Hexapeptide-8 (Argireline).", "primaryUses": [ "Topical cosmetic anti-aging formulations (collagen-quality / fibril organization)" ], "typicalDose": { "range": "2–4", "unit": "% (topical formulation)", "frequency": "twice daily", "route": "topical", "notes": "Cosmetic concentrations. Lipotec clinical study used a 10% liposomal solution delivering 0.01% active peptide." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Puig A, García Antón J, Mangues M. \"A new decorin-like tetrapeptide for optimal organization of collagen fibres.\" Int J Cosmet Sci, 2008;30(2):97-104. PMID: 18377618.", "pmid": "18377618" }, { "type": "pubmed", "citation": "Raikou V, Varvaresou A, Panderi I, Papageorgiou E. \"The efficacy study of the combination of tripeptide-10-citrulline and acetyl hexapeptide-3. A prospective, randomized controlled study.\" J Cosmet Dermatol, 2017;16(2):271-278. PMID: 28150423.", "pmid": "28150423" }, { "type": "manufacturer", "citation": "Lipotec / Lubrizol. \"Decorinyl® (Tripeptide-10 Citrulline) technical data sheet and INCI profile.\"" } ], "interactionCoverage": "none-found", "related": [ "matrixyl", "argireline", "ghk-cu" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." } ], "moleculeClass": "peptide" }, { "id": "degarelix", "name": "Degarelix", "aliases": [ "Firmagon" ], "tier": "full", "category": "sexual-health", "subcategory": "GnRH antagonist", "class": "Synthetic decapeptide GnRH-receptor antagonist for advanced prostate cancer — produces immediate testosterone suppression without the flare characteristic of GnRH agonists.", "tagline": "An approved GnRH antagonist (Firmagon) for advanced prostate cancer: castrate testosterone by day 3 in 96% of men, no flare, but frequent injection-site reactions and an unsettled heart-safety question.", "oneLiner": "A synthetic GnRH-receptor antagonist with multiple non-natural amino acid substitutions designed for sustained-release SC depot delivery. FDA-approved as Firmagon in 2008 for advanced prostate cancer. Key clinical advantage over GnRH agonists: testosterone suppression is immediate (castrate levels by day 3 versus 2–4 weeks with leuprolide) with no initial flare, making it preferred in patients with symptomatic skeletal metastases or spinal cord compression risk where a GnRH-agonist flare could cause acute deterioration.", "sequence": "Ac-D-Nal(2)-D-pClPhe-D-Pal(3)-Ser-4Aph(L-Hor)-D-4Aph(Cbm)-Leu-ILys-Pro-D-Ala-NH2", "molecularFormula": "C82H103ClN18O16", "molecularWeight": 1632.3, "halfLife": { "value": 53, "unit": "days", "range": "terminal half-life ~53 days (80 mg SC maintenance dose)", "notes": "SC depot formulation provides sustained plasma concentrations supporting monthly dosing." }, "fdaStatus": "approved", "approvalDetails": "FDA-approved as Firmagon (degarelix, Ferring Pharmaceuticals, approved December 2008) for treatment of advanced prostate cancer. Loading dose of 240 mg SC (two 120 mg injections) at cycle initiation, followed by monthly 80 mg SC maintenance doses.", "mechanism": "Competitive GnRHR antagonism produces immediate blockade of LH and FSH release; testosterone falls to castrate levels (<50 ng/dL) in approximately 3 days in >96% of patients versus 2–4 weeks with leuprolide. No agonist flare means no transient testosterone surge and no tumor-flare-associated worsening of bone pain, obstructive uropathy, or cord-compression symptoms.", "primaryUses": [ "Advanced prostate cancer — first-line ADT", "Preferred ADT in patients with symptomatic bone metastases or impending cord compression", "Alternative to GnRH agonists in patients at risk of tumor flare" ], "typicalDose": { "range": "240 (loading), 80 (maintenance)", "unit": "mg", "frequency": "monthly maintenance after initial loading dose", "route": "subcutaneous (abdomen)", "notes": "Loading dose: 240 mg total, administered as two separate 120 mg SC injections (each 40 mg/mL). Maintenance: 80 mg SC monthly (20 mg/mL). Injection-site reactions are common (~35%) and typically self-limiting." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Firmagon (degarelix) Prescribing Information. Ferring Pharmaceuticals." }, { "type": "Human", "citation": "Klotz L, et al. \"The efficacy and safety of degarelix: a 12-month, comparative, randomized, open-label, parallel-group phase III study in patients with prostate cancer.\" BJU Int, 2008;102(11):1531-8. PMID: 19035858.", "pmid": "19035858" }, { "type": "Review", "citation": "Doehn C, et al. \"Degarelix for prostate cancer.\" Expert Opin Investig Drugs, 2009;18(6):851-60. PMID: 19453267.", "pmid": "19453267" }, { "type": "Review", "citation": "Doehn C, et al. \"Degarelix and its therapeutic potential in the treatment of prostate cancer.\" Clin Interv Aging, 2009;4:215-23. PMID: 19503784.", "pmid": "19503784" }, { "type": "Human", "citation": "de la Rosette J, et al. \"Efficacy and safety of androgen deprivation therapy after switching from monthly leuprolide to monthly degarelix in patients with prostate cancer.\" Int J Clin Pract, 2011;65(5):559-66. PMID: 21342376.", "pmid": "21342376" }, { "type": "Human", "citation": "Crawford ED, et al. \"A phase III extension trial with a 1-arm crossover from leuprolide to degarelix: comparison of gonadotropin-releasing hormone agonist and antagonist effect on prostate cancer.\" J Urol, 2011;186(3):889-97. PMID: 21788033.", "pmid": "21788033" }, { "type": "Human", "citation": "Smith MR, et al. \"Gonadotropin-releasing hormone blockers and cardiovascular disease risk: analysis of prospective clinical trials of degarelix.\" J Urol, 2011;186(5):1835-42. PMID: 21944083.", "pmid": "21944083" }, { "type": "Review", "citation": " \"Degarelix.\" , 2012. PMID: 31643893.", "pmid": "31643893" }, { "type": "Review", "citation": "Carter NJ, et al. \"Degarelix: a review of its use in patients with prostate cancer.\" Drugs, 2014;74(6):699-712. PMID: 24756432.", "pmid": "24756432" }, { "type": "Review", "citation": "Klotz L. \"Pharmacokinetic and pharmacodynamic profile of degarelix for prostate cancer.\" Expert Opin Drug Metab Toxicol, 2015;11(11):1795-802. PMID: 26513436.", "pmid": "26513436" }, { "type": "Review", "citation": "Barkin J, et al. \"Optimizing subcutaneous injection of the gonadotropin-releasing hormone receptor antagonist degarelix.\" Can J Urol, 2016;23(1):8179-83. PMID: 26892063.", "pmid": "26892063" }, { "type": "Review", "citation": "Uttley L, et al. \"Degarelix for Treating Advanced Hormone-Dependent Prostate Cancer: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.\" Pharmacoeconomics, 2017;35(7):717-726. PMID: 27943135.", "pmid": "27943135" }, { "type": "Human", "citation": "Lopes RD, et al. \"Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Prostate Cancer: The Primary Results of the PRONOUNCE Randomized Trial.\" Circulation, 2021;144(16):1295-1307. PMID: 34459214.", "pmid": "34459214" }, { "type": "Review", "citation": "Zengerling F, et al. \"Degarelix for treating advanced hormone-sensitive prostate cancer.\" Cochrane Database Syst Rev, 2021;8(8):CD012548. PMID: 34350976.", "pmid": "34350976" }, { "type": "Human", "citation": "Devos G, et al. \"ARNEO: A Randomized Phase II Trial of Neoadjuvant Degarelix with or Without Apalutamide Prior to Radical Prostatectomy for High-risk Prostate Cancer.\" Eur Urol, 2023;83(6):508-518. PMID: 36167599.", "pmid": "36167599" }, { "type": "Human", "citation": "Hafron J, et al. \"Study of persistence and adherence to ADT in prostate cancer: relugolix, degarelix, and GnRH agonists in the US.\" Future Oncol, 2025;21(10):1219-1230. PMID: 40189880.", "pmid": "40189880" }, { "type": "Review", "citation": "Odat RM, et al. \"Risk of cardiovascular disease following degarelix versus gonadotropin-releasing hormone agonists in patients with prostate cancer: a systematic review and meta-analysis.\" Urol Oncol, 2025;43(6):359-369. PMID: 39818461.", "pmid": "39818461" } ], "interactionCoverage": "partial", "related": [ "leuprolide", "triptorelin", "goserelin", "cetrorelix", "ganirelix" ], "lastReviewed": "2026-09-27", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "A GnRH antagonist: S2.2.1 covers GnRH and its agonist analogues, not antagonists." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "A GnRH antagonist: S2.2.1 covers GnRH and its agonist analogues, not antagonists." } ], "moleculeClass": "peptide" }, { "id": "dermcidin", "name": "Dermcidin", "aliases": [ "DCD", "DCD-1L", "Sweat antimicrobial peptide" ], "tier": "mid", "category": "immune", "subcategory": "Endogenous antimicrobial peptide (skin)", "class": "Dermcidin is the antimicrobial peptide in human sweat — the skin's constitutive first-line defense against bacterial colonization.", "tagline": "The antibiotic peptide in human sweat, found at lower levels in eczema and acne, and never given to anyone as a treatment.", "oneLiner": "An antimicrobial peptide secreted constantly by sweat glands, whose fragments puncture bacterial membranes through a zinc-stabilised channel.", "sequence": "SSLLEKGLDGAKKAVGGLGKLGKDAVEDLESVGKGAVHDVKDVLDSV (DCD-1L, 47 aa)", "molecularFormula": "C211H344N56O72S", "molecularWeight": 4702.3, "halfLife": { "value": null, "unit": null, "range": "Hours on skin surface", "notes": "Stable in the acidic (pH 5.5), high-salt skin environment. Salt-tolerant, unlike many other AMPs.", "source": { "type": "qualitative", "note": "a description with no figure; no half-life measurement is cited for it" } }, "fdaStatus": "research-only", "approvalDetails": "Not a drug and not approved anywhere. No application appears in Drugs@FDA; its human studies measure it in patients' sweat.", "mechanism": "Unlike most cationic AMPs, dermcidin is anionic. Forms zinc-dependent oligomeric ion channels in bacterial membranes. Constitutive (not infection-induced), salt-stable, and pH-tolerant — distinguishing it from LL-37 and defensins.", "primaryUses": [ "Skin antimicrobial defence (natural)", "Biomarker and drug-lead research" ], "typicalDose": { "range": "N/A", "unit": "N/A", "frequency": "N/A", "route": "endogenous", "notes": "Constitutively secreted at ~1-10 mcg/mL in sweat." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "Schittek B, et al. \"Dermcidin: a novel human antibiotic peptide secreted by sweat glands.\" Nat Immunol, 2001;2(12):1133-7. PMID: 11694882.", "pmid": "11694882" }, { "type": "pubmed", "citation": "Rieg S, et al. \"Deficiency of dermcidin-derived antimicrobial peptides in sweat of patients with atopic dermatitis correlates with an impaired innate defense of human skin in vivo.\" J Immunol, 2005;174(12):8003-10. PMID: 15944307.", "pmid": "15944307" }, { "type": "pubmed", "citation": "Nakano T, et al. \"Reduced expression of dermcidin, a peptide active against propionibacterium acnes, in sweat of patients with acne vulgaris.\" Acta Derm Venereol, 2015;95(7):783-6. PMID: 25673161.", "pmid": "25673161" }, { "type": "pubmed", "citation": "Rieg S, et al. \"Expression of the sweat-derived innate defence antimicrobial peptide dermcidin is not impaired in Staphylococcus aureus colonization or recurrent skin infections.\" Clin Exp Dermatol, 2014;39(2):209-12. PMID: 23782241.", "pmid": "23782241" }, { "type": "pubmed", "citation": "Song C, et al. \"Crystal structure and functional mechanism of a human antimicrobial membrane channel.\" Proc Natl Acad Sci U S A, 2013;110(12):4586-91. PMID: 23426625.", "pmid": "23426625" }, { "type": "other", "citation": "US FDA, Drugs@FDA (openFDA): no application for dermcidin. Read September 30, 2026." } ], "interactionCoverage": "unreviewed", "related": [ "ll-37", "cathelicidin", "hnp-1", "hbd-1" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-21", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "dermorphin", "name": "Dermorphin", "aliases": [ "[D-Ala2]-dermorphin", "Phyllomedusa opioid peptide" ], "tier": "stub", "category": "research", "subcategory": "non-mammalian mu-opioid heptapeptide", "class": "A naturally occurring D-amino-acid-containing heptapeptide isolated from the skin of South American Phyllomedusa frogs, acting as a potent mu-opioid receptor agonist.", "tagline": "⚠ Potent mu-opioid agonist — ~30–40× more potent than morphine; has been misused as a horse-racing doping agent and carries serious overdose/dependence risk. Included for reference and harm-reduction only. Not a therapeutic or \"longevity\" peptide.", "oneLiner": "⚠ A naturally occurring D-amino-acid-containing heptapeptide (Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2) isolated from the skin of Phyllomedusa sauvagei and related South American tree frogs, and one of the few known naturally occurring peptides containing D-amino acids; dermorphin is a highly potent mu-opioid receptor agonist (~30–40× the analgesic potency of morphine by weight in animal models) and has been notoriously misused as a horse-racing performance enhancer (multiple FEI and US Racing Commission positive tests). It is NOT used therapeutically in humans, is NOT a \"peptide for wellness or recovery,\" and has the same overdose/respiratory-depression/dependence risk profile as any other potent opioid — arguably worse given its potency. This entry exists for reference, harm reduction, and scientific completeness only.", "sequence": "Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2", "molecularFormula": "C40H50N8O10", "molecularWeight": 803, "halfLife": { "value": null, "unit": null, "range": "limited human PK", "notes": "Limited human pharmacokinetic data; primary research in rodent analgesia models." }, "fdaStatus": "research-only", "approvalDetails": "Not approved by any regulatory body for any indication. Prohibited in racing animals (FEI, ARCI). Scientific use limited to animal opioid-receptor pharmacology research.", "mechanism": "⚠ Potent mu-opioid receptor (MOR) agonist, selective for MOR over DOR and KOR. MOR activation produces analgesia, respiratory depression, euphoria, constipation, and the full dependence/tolerance profile of opioid receptor agonism. The D-alanine at position 2 confers resistance to proteolytic degradation.", "primaryUses": [ "⚠ No legitimate human therapeutic use", "Research: opioid receptor pharmacology (animal models)", "⚠ Historical: illicit horse-racing performance enhancement (prohibited by FEI / ARCI)" ], "typicalDose": { "range": null, "unit": null, "frequency": null, "route": null, "notes": "⚠ There is no legitimate human dosing. Any self-administration carries serious risk of opioid overdose, respiratory depression, and dependence — risks that are plausibly worse than morphine given the higher per-mg potency. If you are reading this entry because you are considering using dermorphin, please do not; if you are struggling with opioid use or curiosity, SAMHSA National Helpline: 1-800-662-4357 (US), free, 24/7, confidential." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Erspamer V, et al. \"Deltorphins: A family of naturally occurring peptides with high affinity and selectivity for δ opioid binding sites.\" Proc Natl Acad Sci USA, 1989;86:5188-5192. PMID: 2544892.", "pmid": "2544892" }, { "type": "pubmed", "citation": "Broccardo M, et al. \"Pharmacological data on dermorphins, a new class of potent opioid peptides.\" Br J Pharmacol, 1981;73:625-631. PMID: 7195758.", "pmid": "7195758" }, { "type": "manufacturer", "citation": "Association of Racing Commissioners International (ARCI) and FEI prohibited substances list; dermorphin classified as Class 1 prohibited substance in horse racing." } ], "interactionCoverage": "unreviewed", "related": [], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "monitoring": "dermorphin and its analogues, in competition" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "WADA monitored dermorphin as a non-prohibited substance in 2026 and dropped it from the 2027 Monitoring Program without adding it to the List; on its face S0 would cover it." } ], "moleculeClass": "peptide" }, { "id": "desmopressin", "name": "Desmopressin", "aliases": [ "DDAVP", "1-deamino-8-D-arginine vasopressin", "dDAVP", "Stimate", "Minirin", "Noctiva", "Nocdurna" ], "tier": "full", "category": "cardiovascular", "subcategory": "V2-selective vasopressin receptor agonist", "class": "A synthetic V2-selective vasopressin analog (1-deamino-8-D-arginine vasopressin) developed by Ferring in the late 1960s, engineered for long duration, minimal V1 vasopressor activity, and broad clinical utility across central diabetes insipidus, primary nocturnal enuresis, nocturia, hemophilia A, and von Willebrand disease type 1.", "tagline": "DDAVP — the classic V2-selective vasopressin analog. FDA-approved February 1978 for central diabetes insipidus; decades of label expansion added primary nocturnal enuresis, nocturia (Noctiva / Nocdurna), and hemostatic use in mild hemophilia A and type 1 von Willebrand disease. WHO Essential Medicines List.", "oneLiner": "A synthetic nonapeptide with two modifications from native arginine vasopressin: removal of the N-terminal amine (1-deamino) and substitution of D-arginine for L-arginine at position 8. These changes produce >4,000-fold selectivity for the renal V2 receptor (antidiuretic) over the vascular V1a receptor (pressor), give a clinically useful 6–14 hour duration of action (versus 10–35 minutes for vasopressin), and retain the hemostatic activity mediated through release of factor VIII and von Willebrand factor from vascular endothelial Weibel-Palade bodies. Originally developed by Ferring Pharmaceuticals; first clinical use 1974; FDA-approved February 1978 for central diabetes insipidus; subsequently approved for primary nocturnal enuresis in children ≥6, for nocturia (Noctiva intranasal 2017; Nocdurna sublingual 2018), and established by label and off-label use for hemophilia A / von Willebrand type 1. Multiple routes of administration: intranasal, oral tablet, sublingual melt, and intravenous.", "sequence": "Mpa-Tyr-Phe-Gln-Asn-Cys-Pro-D-Arg-Gly-NH2 (disulfide Mpa1-Cys6; Mpa = 3-mercaptopropionic acid)", "molecularFormula": "C46H64N14O12S2", "molecularWeight": 1069.2, "halfLife": { "value": 2, "unit": "hours", "range": "1.5 to 2.5 hours (plasma); terminal about 3 hours, 9 hours in severe renal impairment", "notes": "DDAVP tablet label (SPL effective February 3, 2021): monoexponential plasma half-life 1.5 to 2.5 hours independent of dose; oral bioavailability about 5% of intranasal and 0.16% of intravenous." }, "fdaStatus": "approved", "approvalDetails": "FDA: DDAVP (Ferring) nasal/solution approved February 21, 1978 (NDA 017922, now discontinued); injection March 30, 1984 (NDA 018938); tablets September 6, 1995 (NDA 019955). Stimate nasal spray (March 7, 1994), Noctiva (March 3, 2017) and Nocdurna (June 21, 2018) are listed as discontinued (Drugs@FDA, read September 30, 2026). The tablet label covers central diabetes insipidus, temporary polyuria after head trauma or pituitary surgery, and primary nocturnal enuresis; it contraindicates use in hyponatraemia or a history of it and in severe renal impairment. EU: authorised nationally.", "mechanism": "V2-selective agonist. V2 receptor activation on renal collecting-duct principal cells couples to Gs / adenylate cyclase / cAMP, activating protein kinase A, which phosphorylates aquaporin-2 and drives its insertion into the apical plasma membrane — increasing water permeability and free-water reabsorption. The hemostatic effect arises from V2 receptor activation on vascular endothelial cells (Weibel-Palade bodies), triggering release of preformed von Willebrand factor and (indirectly) factor VIII into plasma — a 2-to-4-fold rise that can correct bleeding in mild hemophilia A and type 1 vWD without transfusion of blood products. The absence of V1a activity means no vasoconstriction and no pressor effect at therapeutic doses.", "primaryUses": [ "Central diabetes insipidus (FDA-approved)", "Primary nocturnal enuresis (FDA-approved oral; pediatric intranasal label discontinued 2007)", "Nocturia due to nocturnal polyuria (FDA-approved sublingual Nocdurna)", "Mild hemophilia A (factor VIII activity >5%)", "Type 1 von Willebrand disease", "Uremic bleeding (off-label)" ], "typicalDose": { "range": "0.05–1.2", "unit": "mg (oral tablet), 10–40 mcg (intranasal), 0.3 mcg/kg (IV for hemostasis)", "frequency": "once to twice daily for chronic indications; single dose for hemostasis", "route": "oral, intranasal, sublingual, intravenous, subcutaneous", "notes": "Dose individualised by indication and response. Severe hyponatremia is the principal safety concern — fluid restriction is essential, particularly in children and elderly. Hemostatic use: maximum benefit at first dose; tachyphylaxis typically after 2–3 consecutive doses." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Ferring Pharmaceuticals. DDAVP (desmopressin acetate) tablets, US prescribing information: indications (central diabetes insipidus; primary nocturnal enuresis), contraindications (hyponatremia or history of hyponatremia; severe renal impairment), warnings (hyponatremia, fluid restriction) and pharmacokinetics (half-life 1.5 to 2.5 hours; terminal 3 hours, 9 hours in severe renal impairment). DailyMed version effective February 3, 2021; read September 30, 2026." }, { "type": "pubmed", "citation": "Richardson DW, et al. \"Desmopressin.\" Ann Intern Med, 1985;103(2):228-39. PMID: 3893256.", "pmid": "3893256" }, { "type": "pubmed", "citation": "Castaman G. \"Desmopressin for the treatment of haemophilia.\" Haemophilia, 2008;14 Suppl 1:15-20. PMID: 18173690.", "pmid": "18173690" }, { "type": "pubmed", "citation": "Leissinger C, et al. \"High-dose DDAVP intranasal spray (Stimate) for the prevention and treatment of bleeding in patients with mild haemophilia A, mild or moderate type 1 von Willebrand disease and symptomatic carriers of haemophilia A.\" Haemophilia, 2001;7(3):258-66. PMID: 11380629.", "pmid": "11380629" }, { "type": "pubmed", "citation": "Viganò GL, et al. \"Subcutaneous desmopressin (DDAVP) shortens the bleeding time in uremia.\" Am J Hematol, 1989;31(1):32-5. PMID: 2705441.", "pmid": "2705441" }, { "type": "pubmed", "citation": "Jin L, et al. \"Effect of desmopressin on platelet aggregation and blood loss in patients undergoing valvular heart surgery.\" Chin Med J (Engl), 2015;128(5):644-7. PMID: 25698197.", "pmid": "25698197" }, { "type": "pubmed", "citation": "Lose G, et al. \"Efficacy of desmopressin (Minirin) in the treatment of nocturia: a double-blind placebo-controlled study in women.\" Am J Obstet Gynecol, 2003;189(4):1106-13. PMID: 14586363.", "pmid": "14586363" }, { "type": "pubmed", "citation": "Cohn JA, et al. \"Desmopressin acetate nasal spray for adults with nocturia.\" Expert Rev Clin Pharmacol, 2017;10(12):1281-1293. PMID: 29048257.", "pmid": "29048257" }, { "type": "pubmed", "citation": "Juul KV, et al. \"Gender difference in antidiuretic response to desmopressin.\" Am J Physiol Renal Physiol, 2011;300(5):F1116-22. PMID: 21367921.", "pmid": "21367921" }, { "type": "pubmed", "citation": "Terho P. \"Desmopressin in nocturnal enuresis.\" J Urol, 1991;145(4):818-20. PMID: 2005708.", "pmid": "2005708" }, { "type": "pubmed", "citation": "Juul KV, et al. \"Desmopressin melt improves response and compliance compared with tablet in treatment of primary monosymptomatic nocturnal enuresis.\" Eur J Pediatr, 2013;172(9):1235-42. PMID: 23677249.", "pmid": "23677249" }, { "type": "pubmed", "citation": "Ikegawa K, et al. \"Use, efficacy, and safety of desmopressin for congenital nephrogenic diabetes insipidus in children: a nationwide survey.\" Endocr J, 2026;73(5):597-605. PMID: 41605691.", "pmid": "41605691" }, { "type": "pubmed", "citation": "Adachi Y, et al. \"Coronary Spastic Angina Induced after Oral Desmopressin (DDAVP) Administration.\" Intern Med, 2016;55(24):3603-3606. PMID: 27980260.", "pmid": "27980260" }, { "type": "fda", "citation": "FDA. Drugs@FDA (openFDA): DDAVP NDA 017922 (February 21, 1978), NDA 018938 (March 30, 1984), NDA 019955 (September 6, 1995); Stimate NDA 020355 (March 7, 1994); Noctiva NDA 201656 (March 3, 2017); Nocdurna NDA 022517 (June 21, 2018). Read September 30, 2026." } ], "interactionCoverage": "label", "related": [ "vasopressin", "terlipressin" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S5", "named": true, "wording": "Desmopressin", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S5", "named": true, "wording": "Desmopressin", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "dihexa", "name": "Dihexa", "aliases": [ "PNB-0408", "N-hexanoic-Tyr-Ile-(6)-aminohexanoic amide" ], "tier": "full", "category": "cognitive", "subcategory": "synaptogenic peptide (HGF/c-Met pathway)", "class": "A synthetic hexapeptide derived from angiotensin IV, engineered for oral bioavailability and BBB penetration.", "tagline": "A modified dipeptide built from angiotensin IV to reach the brain by mouth: rodent memory studies only, no human data, and the paper tying it to HGF/c-Met is retracted.", "oneLiner": "N-hexanoic-Tyr-Ile-(6)-aminohexanoic amide (PNB-0408), an orally active, brain-penetrant analogue of the angiotensin IV fragment Nle1-angiotensin IV, reported to improve memory and synapse formation in rodents; never tested in people.", "sequence": "N-hexanoic-Tyr-Ile-(6)-aminohexanoic amide", "molecularFormula": "C27H44N4O5", "molecularWeight": 504.67, "halfLife": { "value": null, "unit": null, "range": "undetermined in humans", "notes": "No human PK data published." }, "fdaStatus": "research-only", "approvalDetails": "Not approved anywhere and never tested in people in a published study. PubMed lists the 2014 paper that tied dihexa to HGF/c-Met (J Pharmacol Exp Ther 2014;351:390-402) as a retracted publication, as are two related 2011 and 2012 papers from the same group; the 2013 paper that introduced dihexa is not retracted. In 503A Category 2 until its nomination was withdrawn in April 2026; now in no category; PCAC review slated by the end of February 2027.", "mechanism": "Reported to augment hepatocyte growth factor (HGF) binding to the c-Met receptor, promoting synaptogenesis and dendritic spine formation in hippocampal neurons. Promoted as orders of magnitude more potent than BDNF in preclinical synaptogenesis assays. Because c-Met activation is oncogenic in many cancers, there is a theoretical concern about tumor promotion with chronic use.", "primaryUses": [ "Preclinical cognitive enhancement research", "Neurodegenerative disease research (early)" ], "typicalDose": { "range": "8–45", "unit": "mg", "frequency": "daily", "route": "oral (community)", "notes": "Community dosing only. No human clinical trial has established safety or efficacy. Theoretical cancer risk from c-Met activation warrants caution." }, "evidenceLevel": "low", "sources": [ { "type": "Animal", "citation": "Sun X, et al. \"AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway.\" Brain Sci, 2021;11(11). PMID: 34827486.", "pmid": "34827486" }, { "type": "Animal", "citation": "Weiss JB, et al. \"Stem cell, Granulocyte-Colony Stimulating Factor and/or Dihexa to promote limb function recovery in a rat sciatic nerve damage-repair model: Experimental animal studies.\" Ann Med Surg (Lond), 2021;71:102917. PMID: 34703584.", "pmid": "34703584" }, { "type": "pubmed", "citation": "McCoy AT, et al. \"Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents.\" J Pharmacol Exp Ther, 2013;344(1):141-54. PMID: 23055539.", "pmid": "23055539" }, { "type": "pubmed", "citation": "Wright JW, et al. \"The Brain Hepatocyte Growth Factor/c-Met Receptor System: A New Target for the Treatment of Alzheimer's Disease.\" J Alzheimers Dis, 2015;45(4):985-1000. PMID: 25649658.", "pmid": "25649658" }, { "type": "pubmed", "citation": "Wright JW, et al. \"The development of small molecule angiotensin IV analogs to treat Alzheimer's and Parkinson's diseases.\" Prog Neurobiol, 2015;125:26-46. PMID: 25455861.", "pmid": "25455861" }, { "type": "pubmed", "citation": "Wells RG, et al. \"Effects of an Angiotensin IV Analog on 3-Nitropropionic Acid-Induced Huntington's Disease-Like Symptoms in Rats.\" J Huntingtons Dis, 2024;13(1):55-66. PMID: 38489193.", "pmid": "38489193" } ], "interactionCoverage": "unreviewed", "related": [ "semax", "cerebrolysin", "pe-22-28" ], "lastReviewed": "2026-09-27", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptidomimetic", "moleculeClassBasis": "analogue of the angiotensin IV fragment" }, { "id": "dsip", "name": "DSIP", "aliases": [ "Delta Sleep-Inducing Peptide" ], "tier": "full", "category": "cognitive", "subcategory": "sleep-regulatory peptide", "class": "A 9-amino-acid endogenous neuropeptide first isolated from rabbit cerebral venous blood during sleep induction.", "tagline": "A nine-amino-acid peptide isolated from rabbit brain blood in 1977 and named for delta-wave sleep, whose sleep effects in human trials were weak and inconsistent.", "oneLiner": "Delta sleep-inducing peptide, isolated in 1977 by Monnier and Schoenenberger from rabbit cerebral venous blood during artificial induction of delta sleep, with documented effects on sleep architecture, stress tolerance, and chronic pain in limited human studies.", "sequence": "Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu", "molecularFormula": "C35H48N10O15", "molecularWeight": 848.81, "halfLife": { "value": 7, "unit": "minutes", "range": "~7 minutes plasma", "notes": "Very short; biological effects persist despite rapid clearance, suggesting receptor-mediated downstream signaling." }, "fdaStatus": "research-only", "approvalDetails": "Not approved anywhere. Tested in small human trials in the 1980s and 1990s, mostly in insomnia, with weak or inconsistent results; never developed into a medicine.", "mechanism": "Unknown. No gene, precursor protein or receptor for DSIP has been identified, and a 2006 review calls its role as a sleep factor poorly documented. In humans, infused DSIP did not change ACTH, cortisol, growth hormone or prolactin secretion, and in anaesthetised patients it raised heart rate and, paradoxically, reduced EEG delta rhythm.", "primaryUses": [ "Sleep research", "Chronic pain research (limited human data)", "Alcohol and opioid withdrawal research", "Community use for insomnia" ], "typicalDose": { "range": "100–500", "unit": "mcg", "frequency": "once daily at bedtime", "route": "subcutaneous", "notes": "Community dosing only; no clinical standard." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Schneider-Helmert D, et al. \"Acute and delayed effects of DSIP (delta sleep-inducing peptide) on human sleep behavior.\" Int J Clin Pharmacol Ther Toxicol, 1981;19(8):341-5. PMID: 6895513.", "pmid": "6895513" }, { "type": "pubmed", "citation": "Schneider-Helmert D. \"Effects of delta-sleep-inducing peptide on 24-hour sleep-wake behaviour in severe chronic insomnia.\" Eur Neurol, 1987;27(2):120-9. PMID: 3622582.", "pmid": "3622582" }, { "type": "pubmed", "citation": "Bes F, et al. \"Effects of delta sleep-inducing peptide on sleep of chronic insomniac patients. A double-blind study.\" Neuropsychobiology, 1992;26(4):193-7. PMID: 1299794.", "pmid": "1299794" }, { "type": "pubmed", "citation": "Monti JM, et al. \"Study of delta sleep-inducing peptide efficacy in improving sleep on short-term administration to chronic insomniacs.\" Int J Clin Pharmacol Res, 1987;7(2):105-10. PMID: 3583493.", "pmid": "3583493" }, { "type": "pubmed", "citation": "Späth-Schwalbe E, et al. \"Delta-sleep-inducing peptide does not affect CRH and meal-induced ACTH and cortisol secretion.\" Psychoneuroendocrinology, 1995;20(3):231-7. PMID: 7777652.", "pmid": "7777652" }, { "type": "pubmed", "citation": "Giusti M, et al. \"Delta sleep-inducing peptide administration does not influence growth hormone and prolactin secretion in normal women.\" Psychoneuroendocrinology, 1993;18(1):79-84. PMID: 8475226.", "pmid": "8475226" }, { "type": "pubmed", "citation": "Pomfrett CJ, et al. \"Delta sleep-inducing peptide alters bispectral index, the electroencephalogram and heart rate variability when used as an adjunct to isoflurane anaesthesia.\" Eur J Anaesthesiol, 2009;26(2):128-34. PMID: 19142086.", "pmid": "19142086" }, { "type": "pubmed", "citation": "Kovalzon VM, et al. \"Delta sleep-inducing peptide (DSIP): a still unresolved riddle.\" J Neurochem, 2006;97(2):303-9. PMID: 16539679.", "pmid": "16539679" }, { "type": "pubmed", "citation": "Tukhovskaya EA, et al. \"Delta Sleep-Inducing Peptide Recovers Motor Function in SD Rats after Focal Stroke.\" Molecules, 2021;26(17). PMID: 34500605.", "pmid": "34500605" }, { "type": "pubmed", "citation": "Sommerfelt L. \"Reduced sleep in cats after intraperitoneal injection of delta-sleep-inducing peptide (DSIP).\" Neurosci Lett, 1985;58(1):73-7. PMID: 3840239.", "pmid": "3840239" }, { "type": "pubmed", "citation": "Sudakov KV, et al. \"Delta sleep-inducing peptide and nootropic drugs eliminate electroencephalographic and autonomic signs of emotional stress.\" Neurosci Behav Physiol, 1995;25:403-410." } ], "interactionCoverage": "unreviewed", "related": [ "selank", "epithalon" ], "lastReviewed": "2026-09-26", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "dulaglutide", "name": "Dulaglutide", "aliases": [ "Trulicity", "LY2189265" ], "tier": "full", "category": "metabolic", "subcategory": "GLP-1 receptor agonist", "class": "Weekly GLP-1 receptor agonist fused to a modified human IgG4 Fc fragment for extended half-life.", "tagline": "A once-weekly GLP-1 receptor agonist built on an antibody fragment (Trulicity), approved since 2014 for type 2 diabetes in adults and children 10 and older. In REWIND it cut major cardiovascular events by 12%; semaglutide beat it head to head.", "oneLiner": "A fusion protein of two DPP-4-resistant GLP-1 analogue chains linked to a modified human IgG4 Fc fragment, about 63 kDa with a half-life of about 5 days, injected once weekly from 0.75 mg up to 4.5 mg.", "sequence": "GLP-1 analog (Gly8, Glu22, Gly36) × 2 fused to modified IgG4-Fc", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": 5, "unit": "days", "range": "about 5 days", "notes": "Elimination half-life from the Trulicity label; steady state is reached 2 to 4 weeks after starting weekly dosing, and bioavailability is 65% at 0.75 mg and 47% at 1.5 mg." }, "fdaStatus": "approved", "approvalDetails": "FDA-approved as Trulicity (Eli Lilly), BLA 125469, on September 18, 2014 (Drugs@FDA, read September 28, 2026). Current label (published August 10, 2026): glycaemic control in adults and children 10 years and older with type 2 diabetes, and reduction of major adverse cardiovascular events in adults with type 2 diabetes and established cardiovascular disease or multiple risk factors.", "mechanism": "GLP-1 receptor agonism: glucose-dependent insulin release through beta-cell cAMP, lower glucagon and slower gastric emptying (label). DPP-4-resistant changes and the IgG4-Fc fusion give a half-life of about 5 days. Weight loss is modest; semaglutide lowered weight and HbA1c more in the SUSTAIN 7 head-to-head trial.", "primaryUses": [ "Type 2 diabetes mellitus (adults and children 10 years and older)", "Reducing major adverse cardiovascular events in adults with type 2 diabetes (REWIND)" ], "typicalDose": { "range": "0.75–4.5", "unit": "mg", "frequency": "weekly", "route": "subcutaneous", "notes": "Start at 0.75 mg weekly; increase in 1.5 mg steps after at least 4 weeks on each dose, to a maximum of 4.5 mg (label)." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Trulicity (dulaglutide) injection Prescribing Information. Eli Lilly and Company (DailyMed version published 2026-08-10, read 2026-09-28)." }, { "type": "fda-pi", "citation": "US FDA, Drugs@FDA: Trulicity (dulaglutide), BLA 125469, approved 2014-09-18; efficacy supplements approved 2017-01-27, 2018-06-29, 2019-01-15, 2020-02-21, 2020-09-03 and 2022-11-17 (read 2026-09-28)." }, { "type": "pubmed", "citation": "Sanford M. \"Dulaglutide: first global approval.\" Drugs, 2014;74(17):2097-103. PMID: 25367716.", "pmid": "25367716" }, { "type": "pubmed", "citation": "Gerstein HC, et al. \"Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial.\" Lancet, 2019;394(10193):121-130. PMID: 31189511.", "pmid": "31189511" }, { "type": "pubmed", "citation": "Gerstein HC, et al. \"Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial.\" Lancet, 2019;394(10193):131-138. PMID: 31189509.", "pmid": "31189509" }, { "type": "pubmed", "citation": "Cukierman-Yaffe T, et al. \"Effect of dulaglutide on cognitive impairment in type 2 diabetes: an exploratory analysis of the REWIND trial.\" Lancet Neurol, 2020;19(7):582-590. PMID: 32562683.", "pmid": "32562683" }, { "type": "pubmed", "citation": "Pratley RE, et al. \"Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial.\" Lancet Diabetes Endocrinol, 2018;6(4):275-286. PMID: 29397376.", "pmid": "29397376" }, { "type": "pubmed", "citation": "Frias JP, et al. \"Efficacy and Safety of Dulaglutide 3.0 mg and 4.5 mg Versus Dulaglutide 1.5 mg in Metformin-Treated Patients With Type 2 Diabetes in a Randomized Controlled Trial (AWARD-11).\" Diabetes Care, 2021;44(3):765-773. PMID: 33397768.", "pmid": "33397768" }, { "type": "pubmed", "citation": "Tuttle KR, et al. \"Dulaglutide versus insulin glargine in patients with type 2 diabetes and moderate-to-severe chronic kidney disease (AWARD-7): a multicentre, open-label, randomised trial.\" Lancet Diabetes Endocrinol, 2018;6(8):605-617. PMID: 29910024.", "pmid": "29910024" }, { "type": "pubmed", "citation": "Ludvik B, et al. \"Dulaglutide as add-on therapy to SGLT2 inhibitors in patients with inadequately controlled type 2 diabetes (AWARD-10): a 24-week, randomised, double-blind, placebo-controlled trial.\" Lancet Diabetes Endocrinol, 2018;6(5):370-381. PMID: 29483060.", "pmid": "29483060" }, { "type": "pubmed", "citation": "Arslanian SA, et al. \"Once-Weekly Dulaglutide for the Treatment of Youths with Type 2 Diabetes.\" N Engl J Med, 2022;387(5):433-443. PMID: 35658022.", "pmid": "35658022" }, { "type": "pubmed", "citation": "Nicholls SJ, et al. \"Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes.\" N Engl J Med, 2025;393(24):2409-2420. PMID: 41406444.", "pmid": "41406444" }, { "type": "pubmed", "citation": "Guo L, et al. \"Mazdutide versus dulaglutide in Chinese adults with type 2 diabetes.\" Nature, 2026;652(8108):181-188. PMID: 41407860.", "pmid": "41407860" }, { "type": "pubmed", "citation": "Probst L, et al. \"Effects of dulaglutide on alcohol consumption during smoking cessation.\" JCI Insight, 2023;8(22). PMID: 37991022.", "pmid": "37991022" }, { "type": "pubmed", "citation": "Crisafulli S, et al. \"Comparative Gastrointestinal Safety of Dulaglutide, Semaglutide, and Tirzepatide in Adults With Type 2 Diabetes.\" Ann Intern Med, 2026;179(1):1-11. PMID: 41183330.", "pmid": "41183330" }, { "type": "pubmed", "citation": "Derington CG, et al. \"Liraglutide vs Semaglutide vs Dulaglutide in Veterans With Type 2 Diabetes.\" JAMA Netw Open, 2025;8(10):e2537297. PMID: 41082229.", "pmid": "41082229" }, { "type": "pubmed", "citation": "Saeed A, et al. \"Comparison of Semaglutide or Dulaglutide Versus Empagliflozin for Risk for Death and Cardiovascular Outcomes Among Patients With Type 2 Diabetes : Two Target Trial Emulation Studies.\" Ann Intern Med, 2025;178(7):930-939. PMID: 40523289.", "pmid": "40523289" }, { "type": "pubmed", "citation": "Hong B, et al. \"Sodium-Glucose Cotransporter-2 Inhibitors, Dulaglutide, and Risk for Dementia : A Population-Based Cohort Study.\" Ann Intern Med, 2024;177(10):1319-1329. PMID: 39186787.", "pmid": "39186787" } ], "interactionCoverage": "label", "related": [ "semaglutide", "tirzepatide", "liraglutide", "exenatide", "mazdutide" ], "lastReviewed": "2026-09-28", "publishedAt": "2026-04-18", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "protein", "moleculeClassBasis": "Fc fragment" }, { "id": "dynorphin", "name": "Dynorphin", "aliases": [ "Dynorphin A", "Dynorphin B", "Big Dynorphin", "Dyn A" ], "tier": "mid", "category": "cognitive", "subcategory": "Endogenous opioid peptide", "class": "Dynorphin is the endogenous kappa-opioid receptor agonist — unlike the euphoria-producing beta-endorphin and enkephalins, dynorphin produces dysphoria and aversion, serving as the brain's 'anti-reward' signal.", "tagline": "The brain's 'anti-reward' opioid — a kappa-receptor agonist that produces dysphoria rather than euphoria, critical to understanding addiction, stress, and depression.", "oneLiner": "A family of opioid peptides derived from prodynorphin that selectively activate kappa-opioid receptors (KOR), producing dysphoria, stress responses, and anti-reward signaling — the pharmacological opposite of beta-endorphin's euphoric effects.", "sequence": "YGGFLRRIRPKLKWDNQ (Dynorphin A 1-17)", "molecularFormula": "C99H155N29O23", "molecularWeight": 2147.5, "halfLife": { "value": null, "unit": null, "range": "not reported in the sources read", "source": { "type": "none", "note": "searched PubMed on October 1, 2026; no human half-life figure in the sources read" } }, "fdaStatus": "research-only", "approvalDetails": "Not approved as a drug; no application appears in Drugs@FDA (read October 1, 2026). Development around this system is in kappa-opioid antagonists, which block it.", "mechanism": "Selectively binds kappa-opioid receptors (KOR), activating Gi/o signaling. KOR activation in the nucleus accumbens reduces dopamine release (anti-reward), in the dorsal raphe reduces serotonin release (prodepressant), and in the locus coeruleus enhances norepinephrine-mediated stress responses. Upregulated by chronic stress and drug withdrawal, dynorphin/KOR signaling drives the negative affective states that perpetuate addiction cycles.", "primaryUses": [ "Endogenous stress and anti-reward signaling", "Research target for addiction neuroscience (KOR antagonists for relapse prevention)", "Depression research (KOR antagonists as novel antidepressants)", "Pain modulation (spinal dynorphin contributes to chronic pain chronification)" ], "typicalDose": { "range": null, "unit": null, "frequency": null, "route": null, "notes": "Not a medicine. Given intravenously to two subjects at 250 or 1,000 mcg/kg over ten minutes to validate an assay (PMID 9447557)." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Yakovleva T, et al. \"Dysregulation of dynorphins in Alzheimer disease.\" Neurobiol Aging, 2007;28(11):1700-8. PMID: 16914231.", "pmid": "16914231" }, { "type": "pubmed", "citation": "Müller S, et al. \"An HPLC/RIA method for dynorphin A1-13 and its main metabolites in human blood.\" J Pharm Biomed Anal, 1997;16(1):101-9. PMID: 9447557.", "pmid": "9447557" }, { "type": "pubmed", "citation": "Silberring J, et al. \"Characterization of immunoreactive dynorphin B and beta-endorphin in human plasma.\" Peptides, 1998;19(8):1329-37. PMID: 9809646.", "pmid": "9809646" }, { "type": "pubmed", "citation": "Bruchas MR, et al. \"The dynorphin/kappa opioid system as a modulator of stress-induced and pro-addictive behaviors.\" Brain Res, 2010;1314:44-55. PMID: 19716811.", "pmid": "19716811" }, { "type": "pubmed", "citation": "Smith AP, et al. \"Pharmacology of dynorphin.\" Annu Rev Pharmacol Toxicol, 1988;28:123-40. PMID: 2898233.", "pmid": "2898233" }, { "type": "pubmed", "citation": "Goldstein A, et al. \"Dynorphin-(1-13), an extraordinarily potent opioid peptide.\" Proc Natl Acad Sci U S A, 1979;76(12):6666-70. PMID: 230519.", "pmid": "230519" } ], "interactionCoverage": "unreviewed", "related": [ "beta-endorphin", "enkephalin", "dermorphin", "substance-p" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-21", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "ecc5004", "name": "ECC5004", "aliases": [ "AZD5004", "ECC-5004" ], "tier": "stub", "category": "pipeline", "subcategory": "oral GLP-1 peptide (Phase 2)", "class": "An oral peptide GLP-1 receptor agonist developed by Eccogene and licensed to AstraZeneca.", "tagline": "AstraZeneca's oral-peptide GLP-1 candidate (in-licensed from China-based Eccogene in 2023) — Phase 2b in obesity and T2DM; a peptide, not a small molecule, distinguishing it from orforglipron and danuglipron despite the oral route.", "oneLiner": "An oral GLP-1 receptor agonist peptide developed by Eccogene (Shanghai) and licensed by AstraZeneca in November 2023 in a deal potentially worth up to $2B; Phase 1 data demonstrated meaningful oral bioavailability and weight loss, with Phase 2b trials in obesity and T2DM ongoing — notably an actual peptide (not a small molecule like orforglipron).", "sequence": null, "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": "hours", "range": "supports once-daily oral dosing", "notes": "Engineered for oral bioavailability." }, "fdaStatus": "clinical-trials", "approvalDetails": "Not approved. AstraZeneca licensed ex-China global rights from Eccogene in November 2023. Phase 2b program in obesity and T2DM initiated 2024.", "mechanism": "Oral peptide GLP-1 receptor agonism. The peptide chemistry is designed for GI stability and enhanced oral bioavailability without the absorption-enhancer SNAC strategy used by oral semaglutide (Rybelsus). Distinct mechanistically from small-molecule oral GLP-1 agonists (orforglipron, danuglipron) in that it binds the orthosteric GLP-1 peptide site.", "primaryUses": [ "Obesity (Phase 2)", "Type 2 diabetes mellitus (Phase 2)" ], "typicalDose": { "range": null, "unit": "mg", "frequency": "once daily (oral)", "route": "oral", "notes": "Phase 2 doses under evaluation; not publicly finalized." }, "evidenceLevel": "low", "sources": [ { "type": "manufacturer", "citation": "AstraZeneca. Press release: licensing agreement with Eccogene for ECC5004 (AZD5004), November 2023." }, { "type": "manufacturer", "citation": "AstraZeneca pipeline page — AZD5004 Phase 2 status." } ], "interactionCoverage": "none-found", "related": [ "semaglutide", "orforglipron", "danuglipron" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." } ], "moleculeClass": "peptide" }, { "id": "ecnoglutide", "name": "Ecnoglutide", "aliases": [ "XW003", "Xianweiying (branded, China)" ], "tier": "mid", "category": "metabolic", "subcategory": "cAMP-biased GLP-1 receptor agonist", "class": "A long-acting cAMP-biased glucagon-like peptide-1 (GLP-1) receptor agonist.", "tagline": "Sciwind's once-weekly, cAMP-biased GLP-1 analogue (half-life 124-138 h): approved in China for type 2 diabetes (January 2026) and chronic weight management (March 2026) after phase 3 trials, including 13.2% weight loss at 40 weeks. Not FDA- or EMA-approved.", "oneLiner": "A long-acting once-weekly GLP-1 receptor agonist developed by Sciwind Biosciences and Pfizer-partnered, engineered to preferentially activate the cAMP signaling pathway while minimizing β-arrestin recruitment — the first clinical validation of \"GPCR biased agonism\" in metabolic disease, approved by China's NMPA in March 2026 under the brand name Xianweiying.", "sequence": null, "molecularFormula": "C194H304N48O61", "molecularWeight": 4285, "halfLife": { "value": 131, "unit": "hours", "range": "124 to 138 hours at steady state (phase 1)", "source": { "type": "pmid", "pmid": "37364710", "cite": "Guo W, et al. \"Discovery of ecnoglutide - A novel, long-acting, cAMP-biased glucagon-like peptide-1 (GLP-1) analog.\" Mol Metab, 2023;75:101762. PMID: 37364710." } }, "fdaStatus": "not-approved-us", "approvalDetails": "China (NMPA): approved for glycaemic control in adults with type 2 diabetes on January 30, 2026 and for chronic weight management on March 6, 2026 (Sciwind Biosciences announcements). Not FDA-approved (no Drugs@FDA application) and not in EMA's register (both read September 30, 2026).", "mechanism": "Binds and activates GLP-1R with a biased signaling profile — selectively engaging the Gs/cAMP pathway while minimizing β-arrestin recruitment. In theory this separates the beneficial metabolic effects (cAMP-dependent) from some of the adverse events and receptor downregulation associated with β-arrestin recruitment, though the clinical significance of this biased-agonism profile compared to conventional GLP-1 agonists remains a subject of ongoing research.", "primaryUses": [ "Chronic weight management (approved China only)", "Type 2 diabetes (approved China only)" ], "typicalDose": { "range": "0.4–2.4", "unit": "mg", "frequency": "once weekly (trial doses)", "route": "subcutaneous", "notes": "Diabetes trials used 0.4 to 1.2 mg weekly; the obesity trial 1.2, 1.8 or 2.4 mg." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Ji L, et al. \"Efficacy and safety of a biased GLP-1 receptor agonist ecnoglutide in adults with overweight or obesity: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.\" Lancet Diabetes Endocrinol, 2025;13(9):777-789. PMID: 40555243.", "pmid": "40555243" }, { "type": "pubmed", "citation": "Zhu D, et al. \"Efficacy and safety of cAMP signalling-biased GLP-1 analogue ecnoglutide monotherapy versus placebo in patients with type 2 diabetes (EECOH-1): a multi-centre, randomised, double-blind, placebo-controlled, phase 3 trial.\" Nat Commun, 2026;17(1):1420. PMID: 41501026.", "pmid": "41501026" }, { "type": "pubmed", "citation": "He Y, et al. \"Efficacy and safety of cAMP-biased GLP-1 receptor agonist ecnoglutide versus dulaglutide in patients with type 2 diabetes and elevated glucose concentrations on metformin monotherapy (EECOH-2): a 52-week, multicentre, open-label, non-inferiority, randomised, phase 3 trial.\" Lancet Diabetes Endocrinol, 2025;13(10):863-873. PMID: 40854315.", "pmid": "40854315" }, { "type": "pubmed", "citation": "Zhu D, et al. \"Efficacy and safety of GLP-1 analog ecnoglutide in adults with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 2 trial.\" Nat Commun, 2024;15(1):8408. PMID: 39333121.", "pmid": "39333121" }, { "type": "pubmed", "citation": "Guo W, et al. \"Discovery of ecnoglutide - A novel, long-acting, cAMP-biased glucagon-like peptide-1 (GLP-1) analog.\" Mol Metab, 2023;75:101762. PMID: 37364710.", "pmid": "37364710" }, { "type": "news-release", "citation": "Sciwind Biosciences. Ecnoglutide injection approved by China's NMPA for adult type 2 diabetes (PR Newswire, January 30, 2026) and for chronic weight management (PR Newswire, March 6, 2026). Read September 30, 2026." }, { "type": "fda", "citation": "FDA. Drugs@FDA (openFDA): no application for ecnoglutide. Read September 30, 2026." }, { "type": "other", "citation": "European Medicines Agency. Medicines register: no entry for ecnoglutide. Read September 30, 2026." } ], "interactionCoverage": "partial", "related": [ "semaglutide", "liraglutide", "tirzepatide" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": "China (NMPA)", "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "efpeglenatide", "name": "Efpeglenatide", "aliases": [ "HM11260C", "LAPSCA-Exendin-4", "SAR439977" ], "tier": "stub", "category": "pipeline", "subcategory": "long-acting GLP-1 agonist (Phase 3 complete, relicensed)", "class": "A long-acting exendin-4 analog conjugated to an IgG4 Fc fragment via Hanmi's LAPSCOVERY technology for extended half-life.", "tagline": "A weekly-to-monthly exendin-4-based GLP-1 agonist with positive Phase 3 cardiovascular outcomes (AMPLITUDE-O, 2021) — Sanofi returned the license to Hanmi in 2020; Hanmi re-partnered with Innovent in 2020 for China development and with Kailera in 2024 for global development.", "oneLiner": "A long-acting exendin-4 analog built on Hanmi Pharmaceutical's LAPSCOVERY (Long-Acting Protein/Peptide Discovery) platform, which conjugates exendin-4 to an IgG4 Fc fragment via a non-peptidyl flexible linker, producing weekly-to-monthly dosing; AMPLITUDE-O (2021) demonstrated a 27% reduction in MACE in high-CV-risk type 2 diabetes — among the largest GLP-1 CV-outcome benefits reported — but Sanofi returned global rights to Hanmi in 2020 citing strategic-portfolio reasons.", "sequence": "Exendin-4 analog conjugated to IgG4 Fc fragment via PEG linker (LAPSCOVERY platform)", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": 158, "unit": "hours", "range": "~6.5 days", "notes": "Supports once-weekly and once-monthly dosing schedules." }, "fdaStatus": "clinical-trials", "approvalDetails": "Not approved. Phase 3 AMPLITUDE-O completed 2021 with positive CV outcomes; Sanofi returned global rights to Hanmi Pharmaceutical in 2020. Hanmi licensed Greater China rights to Innovent Biologics in 2020 and global ex-China rights to Kailera Therapeutics in 2024 for further development in obesity and T2DM.", "mechanism": "GLP-1 receptor agonism via a long-acting exendin-4 scaffold. The IgG4 Fc conjugation provides FcRn-mediated recycling that dramatically extends plasma half-life beyond native exenatide (~2.4 h) to support weekly-to-monthly administration. Mechanistically identical to other GLP-1 RAs: glucose-dependent insulin secretion, glucagon suppression, delayed gastric emptying, central appetite suppression.", "primaryUses": [ "Type 2 diabetes mellitus with cardiovascular risk (Phase 3)", "Obesity (in development)" ], "typicalDose": { "range": "4–6", "unit": "mg", "frequency": "once weekly", "route": "subcutaneous", "notes": "Phase 3 AMPLITUDE-O used 4 mg and 6 mg weekly dose arms. Monthly schedules explored in earlier studies." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Gerstein HC, et al. \"Cardiovascular and renal outcomes with efpeglenatide in type 2 diabetes (AMPLITUDE-O).\" N Engl J Med, 2021;385:896-907. PMID: 34215025.", "pmid": "34215025" }, { "type": "manufacturer", "citation": "Hanmi Pharmaceutical. Announcement: efpeglenatide global licensing agreement with Kailera Therapeutics, 2024." }, { "type": "clinicaltrials", "citation": "ClinicalTrials.gov NCT03496298 (AMPLITUDE-O): Effect of Efpeglenatide on Cardiovascular Outcomes." } ], "interactionCoverage": "none-found", "related": [ "exenatide", "dulaglutide", "semaglutide" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." } ], "moleculeClass": "peptide-conjugate", "moleculeClassBasis": "conjugated to an IgG4 Fc fragment" }, { "id": "eftansomatropin-alfa", "name": "Eftansomatropin alfa", "aliases": [ "GX-H9", "efpegsomatropin", "Declage" ], "tier": "stub", "category": "pipeline", "subcategory": "long-acting hybrid Fc-fusion growth hormone", "class": "A long-acting recombinant growth hormone fusion protein in which somatropin is linked to a hybrid Fc domain designed to enable weekly or bi-weekly dosing.", "tagline": "Genexine and Handok's long-acting growth hormone candidate — approved in South Korea (Declage, 2025) for pediatric growth hormone deficiency; global partnership with Handok for Korean commercialization.", "oneLiner": "A long-acting recombinant growth hormone fusion protein developed by Genexine (South Korea) using a hybrid Fc (hyFc) half-life extension platform — somatropin is fused to a modified IgD/IgG4 Fc domain that provides FcRn-mediated recycling with minimal effector function. Approved in South Korea as Declage in 2025 for pediatric GH deficiency, with clinical development ongoing in other regions. Has been evaluated for both weekly and every-other-week dosing schedules.", "sequence": "Somatropin fused to hybrid IgD/IgG4 Fc domain", "molecularFormula": null, "molecularWeight": 77000, "halfLife": { "value": 70, "unit": "hours", "range": "approximately 2.5–3.5 days", "notes": "Supports weekly dosing; bi-weekly dosing has also been studied in Phase 2." }, "fdaStatus": "not-approved-us", "approvalDetails": "Approved in South Korea (MFDS) as Declage in 2025 for pediatric growth hormone deficiency, marketed by Handok Inc. Not FDA-approved as of this writing. Phase 3 global program status variable; Genexine has signed regional partnerships (Handok, Tasly) for commercialization in Asia.", "mechanism": "GH receptor agonism by the fused somatropin moiety. The hybrid Fc (hyFc) domain — combining portions of IgD and IgG4 constant regions — enables FcRn-mediated recycling (the same half-life extension mechanism as IgG antibodies) while minimizing FcγR-mediated effector functions such as ADCC and CDC. This produces an extended circulating half-life without the immune activation that full IgG Fc fusion might cause in a hormone replacement context.", "primaryUses": [ "Pediatric growth hormone deficiency (Korea-approved)", "Adult growth hormone deficiency (Phase 2–3 investigated)" ], "typicalDose": { "range": null, "unit": "mg/kg/week", "frequency": "once weekly (primary) or every two weeks (studied)", "route": "subcutaneous", "notes": "Dosing per Korean prescribing information; not established in US populations." }, "evidenceLevel": "medium", "sources": [ { "type": "clinical-trial", "citation": "Kim SG, et al. \"Safety, pharmacokinetics, and pharmacodynamics of GX-H9 (eftansomatropin alfa), a long-acting recombinant human growth hormone, in healthy volunteers and adults with growth hormone deficiency.\" J Clin Pharmacol, 2018;58:621-630." }, { "type": "manufacturer", "citation": "Genexine/Handok. Declage (eftansomatropin alfa) approval announcement, South Korea MFDS, 2025." } ], "interactionCoverage": "none-found", "related": [ "somatropin", "somapacitan", "lonapegsomatropin", "somatrogon" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": "South Korea (MFDS)", "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.2.3", "named": false, "wording": "growth hormone analogues", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "A long-acting growth hormone; approval in South Korea does not lift an S2 listing." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.2.3", "named": false, "wording": "growth hormone analogues", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "A long-acting growth hormone; approval in South Korea does not lift an S2 listing." } ], "moleculeClass": "protein", "moleculeClassBasis": "fusion protein" }, { "id": "elagolix", "name": "Elagolix", "aliases": [ "Orilissa", "NBI-56418" ], "tier": "stub", "category": "sexual-health", "subcategory": "GnRH antagonist (oral)", "class": "A first-in-class oral non-peptide GnRH receptor antagonist for the management of endometriosis-associated pain.", "tagline": "The first oral GnRH antagonist — a non-peptide small molecule that suppresses estrogen production without injection, FDA-approved for endometriosis pain.", "oneLiner": "A non-peptide, orally bioavailable GnRH receptor antagonist that produces dose-dependent suppression of estradiol, offering medical management of endometriosis without the injection burden of peptide GnRH agonists.", "sequence": "Non-peptide small molecule (GnRH receptor antagonist)", "molecularFormula": "C32H30F5N3O5", "molecularWeight": 631.6, "halfLife": { "value": 6, "unit": "hours", "range": "~4–6 hours", "notes": "Short half-life allows partial estrogen suppression at lower doses (avoiding full menopausal symptoms) vs. complete suppression at higher doses." }, "fdaStatus": "approved", "approvalDetails": "FDA-approved in 2018 (Orilissa, AbbVie) for moderate-to-severe endometriosis-associated pain. Available at 150 mg once daily (24 months max) and 200 mg twice daily (6 months max).", "mechanism": "Competitive antagonist at the GnRH receptor (GnRHR) on anterior pituitary gonadotrophs. Blocks endogenous GnRH binding, reducing LH and FSH secretion and consequently suppressing ovarian estradiol production. Unlike GnRH agonists (leuprolide), does not cause initial hormonal flare. Dose-dependent: 150 mg QD produces partial suppression; 200 mg BID produces near-complete suppression.", "primaryUses": [ "Endometriosis-associated pain", "Heavy menstrual bleeding due to uterine fibroids (in combination, as Oriahnn)" ], "typicalDose": { "range": "150–200", "unit": "mg", "frequency": "once or twice daily", "route": "oral", "notes": "150 mg QD for dysmenorrhea-predominant pain; 200 mg BID for deeper/more severe disease. Bone density monitoring recommended." }, "evidenceLevel": "high", "sources": [ { "type": "clinical-trial", "citation": "Taylor HS, et al. \"Treatment of endometriosis-associated pain with elagolix, an oral GnRH antagonist (Elaris EM-I and EM-II).\" N Engl J Med, 2017;377:28-40. PMID: 28525302.", "pmid": "28525302" }, { "type": "fda-pi", "citation": "Orilissa (elagolix) Prescribing Information. AbbVie." } ], "interactionCoverage": "label", "related": [ "leuprolide", "relugolix", "goserelin", "gonadorelin" ], "lastReviewed": "2026-04-20", "publishedAt": "2026-04-20", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "A GnRH antagonist: S2.2.1 covers GnRH and its agonist analogues, not antagonists." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "A GnRH antagonist: S2.2.1 covers GnRH and its agonist analogues, not antagonists." } ], "moleculeClass": "small-molecule", "moleculeClassBasis": "non-peptide" }, { "id": "elsiglutide", "name": "Elsiglutide", "aliases": [ "ZP1846" ], "tier": "stub", "category": "pipeline", "subcategory": "GLP-2 analog (discontinued / early)", "class": "An early Zealand Pharma GLP-2 analog, investigated historically for chemotherapy-induced diarrhea.", "tagline": "Zealand's early GLP-2 analog program (Phase 2 for chemotherapy-induced diarrhea) — superseded by glepaglutide in Zealand's GLP-2 pipeline; retained for pipeline-history completeness.", "oneLiner": "An early GLP-2 analog (Zealand Pharma, ZP1846) investigated in Phase 2 for chemotherapy-induced diarrhea; subsequently superseded within Zealand's pipeline by glepaglutide, which advanced to Phase 3 SBS.", "sequence": "GLP-2 analog (protease-resistant)", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": null, "range": "Phase 2 PK only", "notes": "Limited public PK data." }, "fdaStatus": "discontinued", "approvalDetails": "Not approved. Phase 2 program for chemotherapy-induced diarrhea; superseded by glepaglutide in Zealand Pharma's GLP-2 pipeline.", "mechanism": "GLP-2 receptor agonism — same intestinotrophic mechanism class as teduglutide.", "primaryUses": [ "Historical: chemotherapy-induced diarrhea (Phase 2)" ], "typicalDose": { "range": null, "unit": null, "frequency": null, "route": "subcutaneous", "notes": "Program-level data only." }, "evidenceLevel": "low", "sources": [ { "type": "manufacturer", "citation": "Zealand Pharma pipeline disclosures (historical GLP-2 program ZP1846)." } ], "interactionCoverage": "none-found", "related": [ "teduglutide", "glepaglutide" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "A discontinued drug: S0's own examples include discontinued drugs." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "A discontinued drug: S0's own examples include discontinued drugs." } ], "moleculeClass": "peptide", "moleculeClassBasis": "GLP-2 analog" }, { "id": "endoluten", "name": "Endoluten", "aliases": [ "Pineal peptide bioregulator", "A-8 (pineal peptide preparation)" ], "tier": "stub", "category": "longevity", "subcategory": "Khavinson pineal-derived peptide bioregulator", "class": "A pineal-gland-derived short peptide bioregulator within the Khavinson framework, marketed in Russia as a cytomedine supplement for pineal-axis and neuroendocrine aging.", "tagline": "The Khavinson pineal bioregulator preparation, positioned as a \"precursor/complementary\" product to epithalon (the synthetic AEDG tetrapeptide). Marketed in Russia for neuroendocrine and circadian support in aging. Evidence base is Russian-language Khavinson-group studies with minimal independent replication.", "oneLiner": "A pineal-gland-derived short peptide preparation in the Khavinson cytomedine series, marketed as Endoluten in Russia and CIS markets. Positioned as the natural-extract counterpart to the synthetic tetrapeptide epithalon (Ala-Glu-Asp-Gly / AEDG), which was itself isolated from pineal bioregulator preparations in the 1980s. The regulatory and evidentiary profile is identical to other Khavinson natural-extract cytomedines: Russian nutraceutical status, no FDA/EMA approval, and limited Western peer-reviewed validation.", "sequence": "Pineal-extract mixture; AEDG (epithalon) is the characterized active tetrapeptide from pineal bioregulator preparations", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": null, "range": "Not characterized", "notes": "No published human pharmacokinetic data." }, "fdaStatus": "not-approved-us", "approvalDetails": "Not FDA- or EMA-approved. Sold in Russia and CIS markets as a nutraceutical supplement, not a registered medicine. The synthetic tetrapeptide epithalon, derived from characterization of pineal bioregulator preparations, is itself a research-only compound and is covered in its own encyclopedia entry.", "mechanism": "Proposed to support pineal-axis function and melatonin-related signaling by providing pineal-tissue-specific short peptides. The active tetrapeptide characterized from pineal extracts is epithalon (AEDG), which has been reported in Khavinson-group studies to induce telomerase activity, extend replicative lifespan in cell culture, and modestly extend lifespan in rodent models. As with other Khavinson claims, extensions to humans rest on small, methodologically limited Russian clinical studies and require independent replication.", "primaryUses": [ "Neuroendocrine aging support (Russian nutraceutical positioning)", "Circadian rhythm / sleep-quality support (anecdotal)", "Immune-senescence support (Russian clinical positioning)" ], "typicalDose": { "range": "1–2 capsules", "unit": null, "frequency": "1–2 times daily in 20–30 day courses", "route": "oral", "notes": "Russian nutraceutical dosing. Courses typically repeated 2–4 times per year. No controlled clinical evidence supports specific dosing as efficacious in humans." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Khavinson VK, et al. \"Peptide extension of lifespan and normalization of physiological functions in aged mice.\" Bull Exp Biol Med, 2011;151:480-483." }, { "type": "review", "citation": "Anisimov VN, Khavinson VK. \"Peptide bioregulation of aging: results and prospects.\" Biogerontology, 2010;11:139-149. PMID: 19830585.", "pmid": "19830585" } ], "interactionCoverage": "none-found", "related": [ "epithalon", "pinealon", "cerluten" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": "", "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "endothelin-1", "name": "Endothelin-1", "aliases": [ "ET-1", "Endothelin" ], "tier": "mid", "category": "cardiovascular", "subcategory": "endogenous vasoactive peptide", "class": "A 21-amino-acid vasoconstrictor peptide produced by vascular endothelial cells, the most potent known endogenous vasoconstrictor.", "tagline": "One of the body's most potent vessel constrictors: a drug target for pulmonary hypertension, given to people only in experiments.", "oneLiner": "A 21-amino-acid peptide from blood vessel linings that constricts vessels and airways; its receptor blockers are approved, it is not.", "sequence": "CSCSSLMDKECVYFCHLDIIW (two disulfide bonds: Cys1–Cys15, Cys3–Cys11)", "molecularFormula": "C109H159N25O32S5", "molecularWeight": 2491.9, "halfLife": { "value": null, "unit": null, "range": "about 1 to 2 minutes in plasma after infusion (initial phase); its constriction outlasts it", "source": { "type": "pmid", "pmid": "8379340", "cite": "Weitzberg E. \"Circulatory responses to endothelin-1 and nitric oxide with special reference to endotoxin shock and nitric oxide inhalation.\" Acta Physiol Scand Suppl, 1993;611:1-72. PMID: 8379340." } }, "fdaStatus": "research-only", "approvalDetails": "Not a medicine anywhere; no application appears in Drugs@FDA. Endothelin receptor antagonists are approved separately for pulmonary arterial hypertension.", "mechanism": "Binds ETA receptors (on vascular smooth muscle → vasoconstriction, proliferation) and ETB receptors (on endothelium → NO/prostacyclin release → transient vasodilation; on smooth muscle → vasoconstriction). Net effect is powerful, sustained vasoconstriction. Also promotes fibrosis, inflammation, and cardiac hypertrophy.", "primaryUses": [ "Experimental challenge agent (research)" ], "typicalDose": { "range": null, "unit": null, "frequency": null, "route": null, "notes": "Endogenous hormone. Not administered therapeutically. Endothelin receptor antagonists are the therapeutic class." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Chalmers GW, et al. \"Endothelin-1-induced bronchoconstriction in asthma.\" Am J Respir Crit Care Med, 1997;156(2 Pt 1):382-8. PMID: 9279213.", "pmid": "9279213" }, { "type": "pubmed", "citation": "Hougaard A, et al. \"Intravenous Endothelin-1 Infusion Does Not Induce Aura or Headache in Migraine Patients With Aura.\" Headache, 2020;60(4):724-734. PMID: 31994720.", "pmid": "31994720" }, { "type": "pubmed", "citation": "Eisenberg E, et al. \"Plasma endothelin-1 levels in patients with complex regional pain syndrome.\" Eur J Pain, 2004;8(6):533-8. PMID: 15531221.", "pmid": "15531221" }, { "type": "pubmed", "citation": "Banecki KMRM, et al. \"Endothelin-1 in Health and Disease.\" Int J Mol Sci, 2023;24(14). PMID: 37511055.", "pmid": "37511055" }, { "type": "pubmed", "citation": "Yanagisawa M, et al. \"A novel potent vasoconstrictor peptide produced by vascular endothelial cells.\" Nature, 1988;332(6163):411-5. PMID: 2451132.", "pmid": "2451132" }, { "type": "pubmed", "citation": "Davenport AP, et al. \"Endothelin.\" Pharmacol Rev, 2016;68(2):357-418. PMID: 26956245.", "pmid": "26956245" }, { "type": "pubmed", "citation": "Weitzberg E. \"Circulatory responses to endothelin-1 and nitric oxide with special reference to endotoxin shock and nitric oxide inhalation.\" Acta Physiol Scand Suppl, 1993;611:1-72. PMID: 8379340.", "pmid": "8379340" }, { "type": "other", "citation": "US FDA, Drugs@FDA (openFDA): no application for endothelin-1. Read September 30, 2026." } ], "interactionCoverage": "unreviewed", "related": [ "angiotensin-ii", "vasopressin", "bnp" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-20", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "enkephalin", "name": "Enkephalin", "aliases": [ "Met-Enkephalin", "Leu-Enkephalin", "YGGFM", "YGGFL" ], "tier": "mid", "category": "cognitive", "subcategory": "Endogenous opioid peptide", "class": "Enkephalins are the shortest endogenous opioid peptides — just 5 amino acids — that serve as the primary delta-opioid receptor ligands in local pain circuits and reward pathways.", "tagline": "The body's short-acting local painkillers — five-amino-acid opioid peptides that modulate pain, mood, and gut motility at the synaptic level.", "oneLiner": "Two pentapeptides (Met-enkephalin YGGFM and Leu-enkephalin YGGFL) that bind delta- and mu-opioid receptors in the spinal cord, brainstem, and enteric nervous system, functioning as fast-acting neurotransmitters in local pain and reward circuits.", "sequence": "YGGFM (Met-enkephalin) / YGGFL (Leu-enkephalin)", "molecularFormula": "C27H35N5O7S (Met-enk) / C28H37N5O7 (Leu-enk)", "molecularWeight": 573.67, "halfLife": { "value": null, "unit": null, "range": "not reported in the sources read", "source": { "type": "none", "note": "searched PubMed on October 1, 2026; no human half-life figure in the sources read" } }, "fdaStatus": "research-only", "approvalDetails": "Not approved as a drug; no application appears in Drugs@FDA (read October 1, 2026). Human studies measure enkephalins or their precursor rather than giving them; racecadotril, which blocks their breakdown, is approved in some countries outside the United States.", "mechanism": "Released from preproenkephalin-derived vesicles at synaptic terminals. Met-enkephalin preferentially binds delta-opioid receptors (DOR); both forms also activate mu-opioid receptors. DOR activation inhibits voltage-gated Ca2+ channels and opens K+ channels, hyperpolarizing postsynaptic neurons. Functions in spinal cord dorsal horn (pain gating), nucleus accumbens (reward), amygdala (anxiety modulation), and myenteric plexus (gut motility).", "primaryUses": [ "Endogenous synaptic pain modulation (gate control at spinal level)", "Reward circuit signaling in nucleus accumbens", "GI motility regulation via enteric nervous system", "Research target for non-opioid analgesic strategies (enkephalinase inhibitors)" ], "typicalDose": { "range": null, "unit": null, "frequency": null, "route": null, "notes": "Not a medicine. Given intravenously in one controlled pain study (PMID 8905708), where it had no effect." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Sylvén C, et al. \"Beta-endorphin but not metenkephalin counteracts adenosine-provoked angina pectoris-like pain.\" Neuroreport, 1996;7(12):1982-4. PMID: 8905708.", "pmid": "8905708" }, { "type": "pubmed", "citation": "Breidthardt T, et al. \"Proenkephalin for the early detection of acute kidney injury in hospitalized patients with chronic kidney disease.\" Eur J Clin Invest, 2018;48(10):e12999. PMID: 30009473.", "pmid": "30009473" }, { "type": "pubmed", "citation": "Kamel L, et al. \"Plasma met-enkephalin, beta-endorphin and leu-enkephalin levels in human hepatic encephalopathy.\" East Mediterr Health J, 2007;13(2):257-65. PMID: 17684846.", "pmid": "17684846" }, { "type": "pubmed", "citation": "Zoccali C, et al. \"Plasma met-enkephalin and leu-enkephalin in chronic renal failure.\" Nephrol Dial Transplant, 1987;1(4):219-22. PMID: 3110677.", "pmid": "3110677" }, { "type": "pubmed", "citation": "Ozalp A, et al. \"Determination of methionine-enkephalin and leucine-enkephalin by LC-MS in human plasma: Study of pre-analytical stability.\" Anal Biochem, 2018;559:24-29. PMID: 29981318.", "pmid": "29981318" }, { "type": "pubmed", "citation": "Hughes J, et al. \"Identification of two related pentapeptides from the brain with potent opiate agonist activity.\" Nature, 1975;258(5536):577-80. PMID: 1207728.", "pmid": "1207728" } ], "interactionCoverage": "unreviewed", "related": [ "beta-endorphin", "dynorphin", "dermorphin", "substance-p" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-21", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "interactionCoverage": "none-found", "lastReviewed": "2026-09-30", "publishedAt": "2026-09-30", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-30" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-30" } ], "moleculeClass": "peptide", "tier": "mid", "fdaStatus": "approved", "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Merck Sharp & Dohme. LIPFENDRA (enlicitide) tablets, US prescribing information: indication, dosage (20 mg once daily on an empty stomach), no contraindications, mechanism and pharmacokinetics (effective half-life about 14 hours, terminal about 244 hours), CORALreef trials. DailyMed version effective July 15, 2026; read September 30, 2026." }, { "type": "pubmed", "citation": "Navar AM, et al. \"A Placebo-Controlled Trial of the Oral PCSK9 Inhibitor Enlicitide.\" N Engl J Med, 2026;394(6):529-539. PMID: 41879224.", "pmid": "41879224" }, { "type": "pubmed", "citation": "Ballantyne CM, et al. \"Efficacy and Safety of Oral PCSK9 Inhibitor Enlicitide in Adults With Heterozygous Familial Hypercholesterolemia: A Randomized Clinical Trial.\" JAMA, 2026;335(2):129-139. PMID: 41206969.", "pmid": "41206969" }, { "type": "pubmed", "citation": "Catapano AL, et al. \"Oral PCSK9 Inhibitor Enlicitide Versus Oral Nonstatin Therapies: A Phase 3 Randomized Clinical Trial.\" J Am Coll Cardiol, 2026;88(3):340-352. PMID: 42017875.", "pmid": "42017875" }, { "type": "pubmed", "citation": "Ballantyne CM, et al. \"Phase 2b Randomized Trial of the Oral PCSK9 Inhibitor MK-0616.\" J Am Coll Cardiol, 2023;81(16):1553-1564. PMID: 36889610.", "pmid": "36889610" }, { "type": "fda", "citation": "FDA. Drugs@FDA (openFDA): LIPFENDRA NDA 220848, approved July 15, 2026; and FDA, Novel Drug Approvals for 2026 (content current as of September 28, 2026). Read September 30, 2026." }, { "type": "other", "citation": "European Medicines Agency. Medicines register: no entry for enlicitide. Read September 30, 2026." } ], "id": "enlicitide", "name": "Enlicitide", "aliases": [ "Lipfendra", "Enlicitide decanoate", "MK-0616" ], "category": "cardiovascular", "subcategory": "oral macrocyclic peptide PCSK9 inhibitor", "class": "An oral macrocyclic peptide that binds PCSK9 and stops it from breaking down LDL receptors, lowering LDL cholesterol; FDA-approved as Lipfendra in July 2026.", "tagline": "Merck's oral macrocyclic peptide PCSK9 inhibitor, approved by FDA as Lipfendra on July 15, 2026: one 20 mg tablet a day cut LDL cholesterol by about 56% more than placebo in its phase 3 trial.", "oneLiner": "An oral macrocyclic peptide (enlicitide decanoate) that binds PCSK9 and blocks its binding to hepatic LDL receptors, raising receptor numbers and lowering LDL cholesterol; FDA-approved July 15, 2026 as Lipfendra (Merck, NDA 220848) for adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia.", "sequence": "Macrocyclic peptide; structure in the Lipfendra label, section 11 (enlicitide decanoate)", "molecularFormula": "C82H110FN14O15", "molecularWeight": 1550.8, "halfLife": { "value": 14, "unit": "hours", "range": "effective about 14 hours; terminal about 244 hours", "source": { "type": "label", "ref": "Lipfendra prescribing information, section 12.3 (DailyMed version 2, effective July 15, 2026; read September 30, 2026)" } }, "approvalDetails": "FDA: LIPFENDRA (enlicitide decanoate) tablets, NDA 220848 (Merck Sharp & Dohme), approved July 15, 2026 as an adjunct to diet and exercise to reduce LDL-C in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia (Drugs@FDA; FDA Novel Drug Approvals for 2026). Not in EMA's register (read September 30, 2026).", "mechanism": "Binds PCSK9 and inhibits its binding to LDL receptors on hepatocytes; with less PCSK9-driven receptor degradation, more LDL receptors clear LDL cholesterol from the blood (Lipfendra label, section 12.1).", "primaryUses": [ "LDL-C lowering in adults with hypercholesterolemia, including HeFH (FDA-approved)" ], "typicalDose": { "range": "20", "unit": "mg", "frequency": "once daily, in the morning on an empty stomach", "route": "oral", "notes": "Label: swallow the tablet whole with water, black coffee or plain tea, and wait at least 30 minutes before other food or drink." }, "related": [ "semaglutide", "icotrokinra", "bivalirudin", "nesiritide" ] }, { "id": "epithalon", "name": "Epithalon", "aliases": [ "Epitalon", "Epithalamin", "AEDG" ], "tier": "full", "category": "longevity", "subcategory": "synthetic pineal peptide", "class": "A synthetic tetrapeptide (Ala-Glu-Asp-Gly) modeled on a fragment of the pineal-gland extract epithalamin.", "tagline": "A synthetic pineal tetrapeptide from Vladimir Khavinson's St. Petersburg group, with telomerase and telomere-length data from cell cultures and little human evidence.", "oneLiner": "A short tetrapeptide (Ala-Glu-Asp-Gly) derived from the pineal extract epithalamin, developed by Vladimir Khavinson's group at the St. Petersburg Institute of Bioregulation and Gerontology and reported to induce telomerase activity and telomere elongation in human somatic cells.", "sequence": "Ala-Glu-Asp-Gly", "molecularFormula": "C14H22N4O9", "molecularWeight": 390.35, "halfLife": { "value": null, "unit": null, "range": "not characterised in humans", "notes": "No human pharmacokinetic data in our evidence set. Community protocols use short cycles (10–20 days, 1–2× yearly) rather than chronic dosing." }, "fdaStatus": "research-only", "approvalDetails": "Not approved as a medicine in the US, EU, UK, Canada or Australia. Much of the literature comes from the St. Petersburg group that developed it; independent replication is limited.", "mechanism": "In telomerase-negative human fetal fibroblasts it induced expression of telomerase's catalytic subunit, telomerase activity and telomere elongation (2003); a 2025 study reported dose-dependent telomere lengthening in normal human cells through hTERT and telomerase upregulation, and through ALT activation in breast-cancer cell lines. Animal and extract studies also report melatonin and antioxidant effects. The molecular mechanism is not settled, and most of the literature comes from the developers' group.", "primaryUses": [ "Longevity research (primarily Russian literature)", "Community anti-aging cycles", "Pineal/circadian research" ], "typicalDose": { "range": "5–10", "unit": "mg", "frequency": "daily for 10–20 days (1–2× yearly)", "route": "subcutaneous", "notes": "Community cycling protocols. No clinical standard outside of Russian geriatric clinics." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Khavinson VKh, et al. \"Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells.\" Bull Exp Biol Med, 2003;135(6):590-2. PMID: 12937682.", "pmid": "12937682" }, { "type": "pubmed", "citation": "Al-Dulaimi S, et al. \"Epitalon increases telomere length in human cell lines through telomerase upregulation or ALT activity.\" Biogerontology, 2025;26(5):178. PMID: 40908429.", "pmid": "40908429" }, { "type": "pubmed", "citation": "Khavinson VK, et al. \"Effect of Peptide AEDG on Telomere Length and Mitotic Index of PHA-Stimulated Human Blood Lymphocytes.\" Bull Exp Biol Med, 2019;168(1):141-144. PMID: 31761987.", "pmid": "31761987" }, { "type": "pubmed", "citation": "Khavinson V, et al. \"AEDG Peptide (Epitalon) Stimulates Gene Expression and Protein Synthesis during Neurogenesis: Possible Epigenetic Mechanism.\" Molecules, 2020;25(3). PMID: 32019204.", "pmid": "32019204" }, { "type": "pubmed", "citation": "Khavinson V, et al. \"Pineal-regulating tetrapeptide epitalon improves eye retina condition in retinitis pigmentosa.\" Neuro Endocrinol Lett, 2002;23(4):365-8. PMID: 12195242.", "pmid": "12195242" }, { "type": "pubmed", "citation": "Korkushko OV, et al. \"Geroprotective effect of epithalamine (pineal gland peptide preparation) in elderly subjects with accelerated aging.\" Bull Exp Biol Med, 2006;142(3):356-9. PMID: 17426848.", "pmid": "17426848" }, { "type": "pubmed", "citation": "Anisimov VN, et al. \"Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in female Swiss-derived SHR mice.\" Biogerontology, 2003;4(4):193-202. PMID: 14501183.", "pmid": "14501183" }, { "type": "pubmed", "citation": "Anisimov VN, et al. \"Epithalon decelerates aging and suppresses development of breast adenocarcinomas in transgenic her-2/neu mice.\" Bull Exp Biol Med, 2002;134(2):187-90. PMID: 12459848.", "pmid": "12459848" }, { "type": "pubmed", "citation": "Kossoy G, et al. \"Effect of the synthetic pineal peptide epitalon on spontaneous carcinogenesis in female C3H/He mice.\" In Vivo, 2006;20(2):253-7. PMID: 16634527.", "pmid": "16634527" }, { "type": "pubmed", "citation": "Yue X, et al. \"Epitalon protects against post-ovulatory aging-related damage of mouse oocytes in vitro.\" Aging (Albany NY), 2022;14(7):3191-3202. PMID: 35413689.", "pmid": "35413689" }, { "type": "pubmed", "citation": "Anisimov VN, et al. \"Pineal peptide preparation epithalamin increases the lifespan of fruit flies, mice and rats.\" Mech Ageing Dev, 1998;103(2):123-32. PMID: 9701766.", "pmid": "9701766" }, { "type": "pubmed", "citation": "Araj SK, et al. \"Overview of Epitalon-Highly Bioactive Pineal Tetrapeptide with Promising Properties.\" Int J Mol Sci, 2025;26(6). PMID: 40141333.", "pmid": "40141333" } ], "interactionCoverage": "unreviewed", "related": [ "ss-31", "mots-c", "humanin", "dsip" ], "lastReviewed": "2026-09-26", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "eptifibatide", "name": "Eptifibatide", "aliases": [ "Integrilin", "Barbourin analog" ], "tier": "mid", "category": "cardiovascular", "subcategory": "Platelet glycoprotein IIb/IIIa receptor antagonist (cyclic peptide)", "class": "A cyclic heptapeptide (6 amino acids plus a mercaptopropionyl residue, closed by a disulfide bridge) rationally designed from barbourin — a disintegrin peptide found in the venom of the southeastern pygmy rattlesnake (Sistrurus miliarius barbouri) — that reversibly inhibits fibrinogen binding to the platelet GPIIb/IIIa receptor.", "tagline": "A cyclic heptapeptide that blocks platelet glycoprotein IIb/IIIa, modelled on barbourin from the venom of the southeastern pigmy rattlesnake. FDA-approved as Integrilin on May 18, 1998 for acute coronary syndromes and coronary intervention; now sold as generics.", "oneLiner": "A synthetic cyclic heptapeptide engineered from the disintegrin protein barbourin (from the venom of the southeastern pygmy rattlesnake, Sistrurus miliarius barbouri) by retaining the KGD (Lys-Gly-Asp) motif that confers selective fibrinogen binding to the platelet GPIIb/IIIa receptor. The peptide contains six amino acids plus a mercaptopropionyl (des-amino cysteinyl) group; a disulfide bridge between the terminal cysteine amide and the mercaptopropionyl forms the cyclic structure. FDA-approved May 18, 1998 (Integrilin®, COR Therapeutics / Key Pharmaceuticals, later Millennium Pharmaceuticals / Schering-Plough / Merck; generic availability post-2014) for acute coronary syndromes and percutaneous coronary intervention. Pivotal trials: PURSUIT (NEJM 1998) for unstable angina / non-ST-elevation MI; IMPACT-II (Lancet 1997) and ESPRIT for PCI.", "sequence": "Mpa-Har-Gly-Asp-Trp-Pro-Cys-NH2 (cyclic via Mpa-Cys disulfide; Mpa = mercaptopropionyl; Har = homoarginine)", "molecularFormula": "C35H49N11O9S2", "molecularWeight": 832.0, "halfLife": { "value": 2.5, "unit": "hours", "range": "about 2.5 hours (plasma elimination)", "notes": "Eptifibatide label (DailyMed, SPL effective August 15, 2024): about 25% protein-bound; steady state within 4 to 6 hours of bolus plus infusion.", "source": { "type": "label", "ref": "Eptifibatide injection prescribing information, section 12.3 (DailyMed version 3, effective August 15, 2024; read September 30, 2026)" } }, "fdaStatus": "approved", "approvalDetails": "FDA: Integrilin (NDA 020718) approved May 18, 1998, now listed as discontinued; generic eptifibatide available (15 applications in Drugs@FDA, read September 30, 2026). EU: Eptifibatide Accord authorised in 2016; Integrilin (authorised 1999) withdrawn (EMA register). Indications: acute coronary syndrome managed medically or with PCI; patients undergoing PCI including stenting.", "mechanism": "Reversible, high-affinity antagonist at the platelet glycoprotein IIb/IIIa receptor (integrin αIIbβ3) — the final common pathway for platelet aggregation. The KGD motif within the cyclic heptapeptide structure mimics the RGD recognition sequence of fibrinogen (and vWF and fibronectin) and competitively blocks ligand binding to GPIIb/IIIa. Without GPIIb/IIIa / fibrinogen engagement, platelets cannot cross-link into aggregates regardless of upstream activation signals. Selectivity for αIIbβ3 over other integrins (αvβ3 and others) is conferred by the KGD specificity (versus RGD) — a feature of the parent barbourin peptide. Reversible binding with short plasma half-life means rapid offset after discontinuation (4–8 hours for platelet aggregation to normalise). No immunogenicity (unlike abciximab, which is a chimeric monoclonal antibody fragment and can produce HACA responses).", "primaryUses": [ "Acute coronary syndrome — unstable angina / non-ST-elevation myocardial infarction (FDA-approved)", "Patients undergoing percutaneous coronary intervention including stent placement (FDA-approved)" ], "typicalDose": { "range": "180 mcg/kg bolus, then infusion", "unit": "mcg/kg", "frequency": "IV bolus followed by continuous infusion", "route": "intravenous", "notes": "Label regimens start with a 180 mcg/kg bolus and a continuous infusion; in PCI a second 180 mcg/kg bolus 10 minutes after the first prevents an early dip in levels." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Eptifibatide injection, US prescribing information (Avenacy). DailyMed version effective August 15, 2024; read September 30, 2026." }, { "type": "pubmed", "citation": " \"Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes.\" N Engl J Med, 1998;339(7):436-43. PMID: 9705684.", "pmid": "9705684" }, { "type": "pubmed", "citation": " \"Novel dosing regimen of eptifibatide in planned coronary stent implantation (ESPRIT): a randomised, placebo-controlled trial.\" Lancet, 2000;356(9247):2037-44. PMID: 11145489.", "pmid": "11145489" }, { "type": "pubmed", "citation": " \"Randomised placebo-controlled trial of effect of eptifibatide on complications of percutaneous coronary intervention: IMPACT-II. Integrilin to Minimise Platelet Aggregation and Coronary Thrombosis-II.\" Lancet, 1997;349(9063):1422-8. PMID: 9164315.", "pmid": "9164315" }, { "type": "pubmed", "citation": "Adeoye O, et al. \"Adjunctive Intravenous Argatroban or Eptifibatide for Ischemic Stroke.\" N Engl J Med, 2024;391(9):810-820. PMID: 39231343.", "pmid": "39231343" }, { "type": "pubmed", "citation": "Phillips DR, et al. \"Clinical pharmacology of eptifibatide.\" Am J Cardiol, 1997;80(4A):11B-20B. PMID: 9291241.", "pmid": "9291241" }, { "type": "pubmed", "citation": "Pothineni NV, et al. \"Eptifibatide-Induced Thrombocytopenia--When Inhibitor Turns Killer.\" Am J Ther, 2016;23(1):e298-9. PMID: 24368608.", "pmid": "24368608" }, { "type": "fda", "citation": "FDA. Drugs@FDA (openFDA): Integrilin NDA 020718, approved May 18, 1998, discontinued; 15 eptifibatide applications. Read September 30, 2026." }, { "type": "other", "citation": "European Medicines Agency. Medicines register: Eptifibatide Accord, authorised January 11, 2016; Integrilin, authorised July 1, 1999, withdrawn. Read September 30, 2026." } ], "interactionCoverage": "label", "related": [ "bivalirudin" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "erythropoietin", "name": "Erythropoietin (EPO)", "aliases": [ "EPO", "Epoetin alfa", "Epoetin beta", "Darbepoetin alfa", "Epogen", "Procrit", "Aranesp", "rHuEPO", "rhEpo" ], "tier": "full", "category": "cardiovascular", "subcategory": "erythropoiesis-stimulating glycoprotein hormone", "class": "A 165-amino-acid glycoprotein hormone produced primarily by peritubular cells of the renal cortex in response to hypoxia. Clinical products are recombinant versions (epoetin alfa/beta) or longer-acting engineered analogs (darbepoetin alfa, methoxy PEG-epoetin β).", "tagline": "A glycoprotein hormone that drives red blood cell production; recombinant forms are FDA-approved standards of care for anemia of chronic kidney disease and chemotherapy-induced anemia, and have a notorious history of misuse in endurance sport.", "oneLiner": "An erythropoiesis-stimulating agent (ESA) that binds EPO receptors on CD34+ hematopoietic progenitors to drive red blood cell maturation, widely used in renal and oncology medicine, and a central figure in the sport-doping history of the late 20th and early 21st centuries.", "sequence": "165-amino-acid glycoprotein (too long to list inline; protein rather than short peptide)", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": null, "range": "4 to 13 hours after IV epoetin alfa (kidney disease); peak 5 to 24 hours after SC", "notes": "Epogen label (SPL effective June 23, 2026). A glycoprotein of about 30.4 kDa whose exact mass varies with glycosylation, so no molecular weight is recorded for matching." }, "fdaStatus": "approved", "approvalDetails": "FDA: Epogen/Procrit (epoetin alfa, BLA 103234) approved June 1, 1989; biosimilar Retacrit (epoetin alfa-epbx) May 15, 2018; analogues Aranesp (darbepoetin alfa) September 17, 2001 and Mircera November 14, 2007 (Drugs@FDA, read September 30, 2026). Epogen's label indications include anaemia from chronic kidney disease, zidovudine in HIV and myelosuppressive chemotherapy, under a boxed warning for death, myocardial infarction, stroke, venous thromboembolism, vascular-access thrombosis and tumour progression or recurrence. EU: several epoetins centrally authorised (EMA register).", "mechanism": "Binds the EPO receptor (EPOR, a member of the type I cytokine receptor family) on the surface of CD34+ hematopoietic progenitor cells in bone marrow. Receptor dimerization activates JAK2/STAT5 signaling, promoting erythroid progenitor proliferation, differentiation, and survival (anti-apoptosis). Endogenous EPO is upregulated by hypoxia via HIF-2α-mediated transcription in renal peritubular cells. Tissue-protective effects (anti-apoptosis, anti-inflammation) have also been observed in heart, brain, and kidney in preclinical studies, though these remain investigational clinically.", "primaryUses": [ "Anemia of chronic kidney disease", "Chemotherapy-induced anemia (non-myeloid malignancies)", "Anemia associated with zidovudine in HIV", "Reduction of perioperative transfusion in elective surgery", "Illicit performance-enhancement in endurance sport (WADA-banned)" ], "typicalDose": { "range": "50–300", "unit": "IU/kg", "frequency": "2–3x weekly (epoetin); every 2–4 weeks (darbepoetin)", "route": "intravenous or subcutaneous", "notes": "Dose titrated to hemoglobin target (typically 10–11 g/dL in CKD; higher targets increase cardiovascular risk). Darbepoetin is dosed in mcg/kg, not IU/kg." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Amgen. EPOGEN (epoetin alfa) injection, US prescribing information: boxed warning (death, myocardial infarction, stroke, venous thromboembolism, thrombosis of vascular access, tumor progression or recurrence); indications; contraindications (uncontrolled hypertension, PRCA after erythropoietin protein drugs, serious allergic reactions, benzyl alcohol in neonates); half-life 4 to 13 hours IV in CKD. DailyMed version effective June 23, 2026; read September 30, 2026." }, { "type": "pubmed", "citation": "Jelkmann W. \"Physiology and pharmacology of erythropoietin.\" Transfus Med Hemother, 2013;40(5):302-9. PMID: 24273483.", "pmid": "24273483" }, { "type": "pubmed", "citation": "Provenzano R, et al. \"Once-weekly epoetin alfa for treating the anemia of chronic kidney disease.\" Clin Nephrol, 2004;61(6):392-405. PMID: 15224803.", "pmid": "15224803" }, { "type": "pubmed", "citation": "McCullough PA, et al. \"Cardiovascular toxicity of epoetin-alfa in patients with chronic kidney disease.\" Am J Nephrol, 2013;37(6):549-58. PMID: 23735819.", "pmid": "23735819" }, { "type": "pubmed", "citation": "Cournoyer D, et al. \"Anti-erythropoietin antibody-mediated pure red cell aplasia after treatment with recombinant erythropoietin products: recommendations for minimization of risk.\" J Am Soc Nephrol, 2004;15(10):2728-34. PMID: 15466278.", "pmid": "15466278" }, { "type": "pubmed", "citation": "Macdougall IC, et al. \"Incidence of erythropoietin antibody-mediated pure red cell aplasia: the Prospective Immunogenicity Surveillance Registry (PRIMS).\" Nephrol Dial Transplant, 2015;30(3):451-60. PMID: 25239637.", "pmid": "25239637" }, { "type": "pubmed", "citation": "Thadhani R, et al. \"Switching from Epoetin Alfa (Epogen®) to Epoetin Alfa-Epbx (RetacritTM) Using a Specified Dosing Algorithm: A Randomized, Non-Inferiority Study in Adults on Hemodialysis.\" Am J Nephrol, 2018;48(3):214-224. PMID: 30196301.", "pmid": "30196301" }, { "type": "pubmed", "citation": "Fishbane S, et al. \"Roxadustat Versus Epoetin Alfa for Treating Anemia in Patients with Chronic Kidney Disease on Dialysis: Results from the Randomized Phase 3 ROCKIES Study.\" J Am Soc Nephrol, 2022;33(4):850-866. PMID: 35361724.", "pmid": "35361724" }, { "type": "pubmed", "citation": "Wisnowski JL, et al. \"Brain Injury Outcomes after Adjuvant Erythropoietin Neuroprotection for Moderate or Severe Neonatal Hypoxic-Ischemic Encephalopathy: A Report from the HEAL Trial.\" Dev Neurosci, 2024;46(5):285-296. PMID: 37906983.", "pmid": "37906983" }, { "type": "pubmed", "citation": "Bradbury KE, et al. \"Impact of intravenous iron or exogenous erythropoietin on hemoglobin mass, exercise performance, and acute mountain sickness during altitude acclimatization.\" J Appl Physiol (1985), 2025;139(4):954-963. PMID: 40912897.", "pmid": "40912897" }, { "type": "fda", "citation": "FDA. Drugs@FDA (openFDA): Epogen/Procrit BLA 103234 (June 1, 1989); Retacrit BLA 125545 (May 15, 2018); Aranesp BLA 103951 (September 17, 2001); Mircera BLA 125164 (November 14, 2007). Read September 30, 2026." }, { "type": "other", "citation": "European Medicines Agency. Medicines register: epoetins centrally authorised include Abseamed, Binocrit, Epoetin Alfa Hexal, Retacrit, Silapo, NeoRecormon, Biopoin and Eporatio, with Aranesp and Mircera. Read September 30, 2026." } ], "interactionCoverage": "partial", "related": [ "somatropin", "hcg" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-20", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.1.1", "named": true, "wording": "erythropoietins (EPO)", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.1.1", "named": true, "wording": "erythropoietins (EPO)", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "protein", "moleculeClassBasis": "glycoprotein" }, { "id": "examorelin", "name": "Examorelin", "aliases": [ "Hexarelin", "EP 23905", "MF-6003" ], "tier": "stub", "category": "research", "subcategory": "GHRP / ghrelin receptor agonist", "class": "The international nonproprietary name (INN) of hexarelin, a synthetic hexapeptide GH secretagogue (ghrelin-receptor agonist); PubChem files both names under CID 6918297.", "tagline": "Examorelin is hexarelin under its official nonproprietary name: the same GH-releasing hexapeptide, never approved. See the hexarelin entry for the evidence.", "oneLiner": "The international nonproprietary name for hexarelin (His-D-2-Me-Trp-Ala-Trp-D-Phe-Lys-NH2), a synthetic growth hormone-releasing hexapeptide studied in small human studies in the 1990s and never approved. PubChem files examorelin, hexarelin, EP 23905 and MF-6003 under one record, CID 6918297.", "sequence": "His-D-2-Me-Trp-Ala-Trp-D-Phe-Lys-NH2", "molecularFormula": "C47H58N12O6", "molecularWeight": 887.0, "halfLife": { "value": null, "unit": null, "range": "not measured in humans", "notes": "Intravenous half-life 76 minutes in rats (2000) and 120 minutes in dogs (1995). The '55 minutes' once given here is the half-life of the growth hormone it releases (1994)." }, "fdaStatus": "research-only", "approvalDetails": "Never approved in any jurisdiction, under this name or as hexarelin.", "mechanism": "The same molecule as hexarelin: a ghrelin-receptor (GHS-R1a) agonist that releases growth hormone, with smaller ACTH, cortisol and prolactin rises, and binds CD36 in heart tissue.", "primaryUses": [ "Research: GH secretagogue receptor pharmacology", "Historical: GH stimulation testing (small clinical series)" ], "typicalDose": { "range": null, "unit": null, "frequency": null, "route": null, "notes": "No approved clinical dose; research use only." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "Imbimbo BP, et al. \"Growth hormone-releasing activity of hexarelin in humans. A dose-response study.\" Eur J Clin Pharmacol, 1994;46(5):421-5. PMID: 7957536.", "pmid": "7957536" }, { "type": "pubmed", "citation": "Deghenghi R, et al. \"GH-releasing activity of Hexarelin, a new growth hormone releasing peptide, in infant and adult rats.\" Life Sci, 1994;54(18):1321-8. PMID: 7910650.", "pmid": "7910650" } ], "interactionCoverage": "unreviewed", "related": [ "hexarelin", "ghrp-2", "ghrp-6", "ipamorelin" ], "lastReviewed": "2026-09-26", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.2.4", "named": true, "wording": "examorelin (hexarelin)", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "The same molecule as hexarelin." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.2.4", "named": true, "wording": "examorelin (hexarelin)", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "The same molecule as hexarelin." } ], "moleculeClass": "peptide" }, { "id": "exenatide", "name": "Exenatide", "aliases": [ "Byetta", "Bydureon", "Bydureon BCise", "Exendin-4" ], "tier": "full", "category": "metabolic", "subcategory": "GLP-1 receptor agonist", "class": "Synthetic version of exendin-4, a 39-amino-acid peptide originally isolated from Gila monster (Heloderma suspectum) venom.", "tagline": "The first GLP-1 receptor agonist (Byetta, 2005), a synthetic copy of a Gila monster venom peptide: safe for the heart in EXSCEL without proving benefit, outperformed by weekly semaglutide head to head, and negative in a phase 3 Parkinson's trial.", "oneLiner": "A synthetic 39-amino-acid peptide amide (exendin-4), originally identified in the lizard Heloderma suspectum, that activates the GLP-1 receptor; its half-life of 2.4 hours (Byetta label) means twice-daily injections, while the weekly forms used slow-release microspheres.", "sequence": "HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS", "molecularFormula": "C184H282N50O60S", "molecularWeight": 4186.6, "halfLife": { "value": 2.4, "unit": "hours", "range": "2.4 h (Byetta); measurable for about 10 h after a dose", "notes": "From the Byetta label; independent of dose. The weekly forms released exenatide from microspheres over days." }, "fdaStatus": "approved", "approvalDetails": "FDA-approved: Byetta (twice daily; NDA 021773, April 28, 2005), Bydureon (weekly; NDA 022200, January 27, 2012) and Bydureon BCise (NDA 209210, October 20, 2017). Drugs@FDA lists all three applications as discontinued (read September 28, 2026), while a Byetta label (AstraZeneca) remains on DailyMed and a generic exenatide injection (Amneal, ANDA 206697) was approved November 19, 2024.", "mechanism": "Agonist at the GLP-1 receptor: glucose-dependent insulin secretion, lower glucagon and slower gastric emptying, which is why Byetta is injected within an hour before the two main meals. Its 2.4-hour half-life (label) gives twice-daily dosing; the weekly forms used slow-release microspheres.", "primaryUses": [ "Type 2 diabetes mellitus" ], "typicalDose": { "range": "5–10 mcg twice daily (Byetta) / 2 mg weekly (weekly forms)", "unit": "", "frequency": "varies by formulation", "route": "subcutaneous", "notes": "Byetta label: 5 mcg twice daily within 60 minutes before the two main meals, increased to 10 mcg after a month. The weekly forms (now discontinued) and the trials used 2 mg once weekly." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Byetta (exenatide) injection Prescribing Information. AstraZeneca (DailyMed version of 2025-09-08, read 2026-09-28)." }, { "type": "fda-pi", "citation": "US FDA, Drugs@FDA: Byetta NDA 021773 (April 28, 2005), Bydureon NDA 022200 (January 27, 2012), Bydureon BCise NDA 209210 (October 20, 2017), all listed as discontinued; exenatide injection ANDA 206697 (Amneal, November 19, 2024) (read 2026-09-28)." }, { "type": "Human", "citation": "Holman RR, et al. \"Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes.\" N Engl J Med, 2017;377(13):1228-1239. PMID: 28910237.", "pmid": "28910237" }, { "type": "Human", "citation": "Ahmann AJ, et al. \"Efficacy and Safety of Once-Weekly Semaglutide Versus Exenatide ER in Subjects With Type 2 Diabetes (SUSTAIN 3): A 56-Week, Open-Label, Randomized Clinical Trial.\" Diabetes Care, 2018;41(2):258-266. PMID: 29246950.", "pmid": "29246950" }, { "type": "Human", "citation": "Ruff CT, et al. \"Subcutaneous infusion of exenatide and cardiovascular outcomes in type 2 diabetes: a non-inferiority randomized controlled trial.\" Nat Med, 2022;28(1):89-95. PMID: 34873344.", "pmid": "34873344" }, { "type": "Human", "citation": "Tamborlane WV, et al. \"Once-Weekly Exenatide in Youth With Type 2 Diabetes.\" Diabetes Care, 2022;45(8):1833-1840. PMID: 35679098.", "pmid": "35679098" }, { "type": "Human", "citation": "Athauda D, et al. \"Exenatide once weekly versus placebo in Parkinson's disease: a randomised, double-blind, placebo-controlled trial.\" Lancet, 2017;390(10103):1664-1675. PMID: 28781108.", "pmid": "28781108" }, { "type": "Human", "citation": "Vijiaratnam N, et al. \"Exenatide once a week versus placebo as a potential disease-modifying treatment for people with Parkinson's disease in the UK: a phase 3, multicentre, double-blind, parallel-group, randomised, placebo-controlled trial.\" Lancet, 2025;405(10479):627-636. PMID: 39919773.", "pmid": "39919773" }, { "type": "Human", "citation": "Mullins RJ, et al. \"A Pilot Study of Exenatide Actions in Alzheimer's Disease.\" Curr Alzheimer Res, 2019;16(8):741-752. PMID: 31518224.", "pmid": "31518224" }, { "type": "Human", "citation": "Mitchell JL, et al. \"The effect of GLP-1RA exenatide on idiopathic intracranial hypertension: a randomized clinical trial.\" Brain, 2023;146(5):1821-1830. PMID: 36907221.", "pmid": "36907221" }, { "type": "Human", "citation": "Patino LR, et al. \"A double-blind, placebo-controlled trial of exenatide for the treatment of olanzapine-related weight gain in obese and overweight adults.\" J Affect Disord, 2025;382:116-122. PMID: 40203970.", "pmid": "40203970" }, { "type": "Human", "citation": "Issar T, et al. \"Effect of exenatide on peripheral nerve excitability in type 2 diabetes.\" Clin Neurophysiol, 2021;132(10):2532-2539. PMID: 34455311.", "pmid": "34455311" }, { "type": "Human", "citation": "Tripathy NR, et al. \"Exenatide and acute pancreatitis.\" J Assoc Physicians India, 2008;56:987-8. PMID: 19322980.", "pmid": "19322980" } ], "interactionCoverage": "label", "related": [ "liraglutide", "semaglutide", "lixisenatide" ], "lastReviewed": "2026-09-28", "publishedAt": "2026-04-18", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "felypressin", "name": "Felypressin", "aliases": [ "Octapressin", "PLV-2", "2-phenylalanine-8-lysine-vasopressin" ], "tier": "mid", "category": "cardiovascular", "subcategory": "V1a-selective vasopressin receptor agonist (dental vasoconstrictor)", "class": "A synthetic vasopressin analog (2-phenylalanine-8-lysine-vasopressin) marketed primarily as a vasoconstrictor component of dental local-anaesthetic formulations in Europe, Japan, Brazil, and some Commonwealth countries; never FDA-approved in the United States, where dental local anaesthetics use epinephrine as the standard vasoconstrictor.", "tagline": "The vasopressin analogue added to prilocaine dental anaesthetics instead of adrenaline, approved widely abroad and never in the US.", "oneLiner": "A synthetic vasopressin analogue that narrows blood vessels through V1 receptors, used to make dental anaesthetics last longer.", "sequence": "Cys-Phe-Phe-Gln-Asn-Cys-Pro-Lys-Gly-NH2 (disulfide Cys1-Cys6)", "molecularFormula": "C46H65N13O11S2", "molecularWeight": 1040.23, "halfLife": { "value": null, "unit": null, "range": "short; local activity", "notes": "Used as a local vasoconstrictor in dental-anaesthetic cartridges; systemic exposure minimal at dental doses (0.03 IU/mL × 1.8 mL cartridge = 0.054 IU total per cartridge, delivered locally).", "source": { "type": "qualitative", "note": "a description with no figure; no half-life measurement is cited for it" } }, "fdaStatus": "not-approved-us", "approvalDetails": "Approved as an ingredient of prilocaine dental anaesthetic products in the UK, much of Europe, Japan, Brazil and Australia, among others. Never approved in the US; no application appears in Drugs@FDA.", "mechanism": "Selective V1a vasopressin receptor agonist — the phenylalanine-2 and lysine-8 substitutions of felypressin retain V1a binding and vasoconstrictor activity while minimising V2 antidiuretic activity. Local injection into oral tissues produces vasoconstriction in the submucosal microvasculature (V1a on arteriolar smooth muscle), reducing bleeding at the surgical site and prolonging the duration of the co-administered local anaesthetic by slowing its washout. Unlike epinephrine, felypressin does not engage β1 cardiac adrenergic receptors and therefore avoids direct positive-chronotropic and positive-inotropic effects — a safety advantage in patients with arrhythmia history, uncontrolled hypertension, or catecholamine-sensitive cardiovascular disease. Potential concerns include coronary artery vasoconstriction at higher doses (V1a-mediated), which makes it still relatively contraindicated in severe coronary artery disease. Uterine V1a receptors are also engaged, so felypressin is avoided in obstetric patients.", "primaryUses": [ "Vasoconstrictor in prilocaine dental and minor-surgery anaesthetics (outside the US)" ], "typicalDose": { "range": "0.03 IU/mL (in local-anaesthetic cartridge)", "unit": "IU per dental cartridge (1.8 mL)", "frequency": "single local injection per site", "route": "local submucosal injection (dental)", "notes": "⚠ Not FDA-approved in the US. Used as a vasoconstrictor component in prilocaine-felypressin dental cartridges. Relatively contraindicated in obstetric patients (V1a uterine activity) and in severe coronary artery disease (coronary V1a vasoconstriction). Maximum of approximately 8 cartridges per appointment for adult patients." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "Sunada K, et al. \"Clinically safe dosage of felypressin for patients with essential hypertension.\" Anesth Prog, 1996;43(4):108-15. PMID: 10323116.", "pmid": "10323116" }, { "type": "pubmed", "citation": "Bronzo AL, et al. \"Felypressin increases blood pressure during dental procedures in hypertensive patients.\" Arq Bras Cardiol, 2012;99(2):724-31. PMID: 22735869.", "pmid": "22735869" }, { "type": "pubmed", "citation": "Howells RE, et al. \"A comparison of the side effects of prilocaine with felypressin and lignocaine with adrenaline in large loop excision of the transformation zone of the cervix: results of a randomised trial.\" BJOG, 2000;107(1):28-32. PMID: 10645858.", "pmid": "10645858" }, { "type": "pubmed", "citation": "Cohn JN, et al. \"Systemic vasoconstrictor and renal vasodilator effects of PLV-2 (octapressin) in man.\" Circulation, 1968;38(1):151-7. PMID: 11712284.", "pmid": "11712284" }, { "type": "pubmed", "citation": "Jastak JT, et al. \"Vasoconstrictors and local anesthesia: a review and rationale for use.\" J Am Dent Assoc, 1983;107(4):623-30. PMID: 6355236.", "pmid": "6355236" }, { "type": "other", "citation": "US FDA, Drugs@FDA (openFDA): no application for felypressin. Read September 30, 2026." } ], "interactionCoverage": "studied", "related": [ "vasopressin", "terlipressin", "desmopressin" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": "UK, Germany, Japan, Brazil, Australia, Scandinavia", "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S5", "named": true, "wording": "Local administration of felypressin in dental anaesthesia", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "exception": "local administration of felypressin in dental anaesthesia is permitted", "remark": "The List mentions felypressin only to exempt local dental use; given any other way it is an S5 masking agent." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S5", "named": true, "wording": "Local administration of felypressin in dental anaesthesia", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "exception": "local administration of felypressin in dental anaesthesia is permitted", "remark": "The List mentions felypressin only to exempt local dental use; given any other way it is an S5 masking agent." } ], "moleculeClass": "peptide" }, { "id": "fgl-peptide", "name": "FGL Peptide", "aliases": [ "FGL", "NCAM-derived FGL peptide", "EVYVVAENQQGKSKA" ], "tier": "stub", "category": "cognitive", "subcategory": "NCAM-mimetic peptide", "class": "A synthetic peptide fragment of the neural cell adhesion molecule (NCAM) that mimics the FGL motif interacting with fibroblast growth factor receptor (FGFR); investigated as a neurogenic, neuroprotective, and cognition-enhancing agent in preclinical models.", "tagline": "A 15-amino-acid synthetic peptide derived from the second fibronectin-type-III module of NCAM, designed to mimic NCAM's interaction with FGFR1 and reproduce downstream neurogenic signaling. Preclinical cognition and neuroprotection data only; no human clinical trials; research-only.", "oneLiner": "A 15-residue peptide (EVYVVAENQQGKSKA) mimicking a binding motif of the second fibronectin type-III (F3) module of the neural cell adhesion molecule (NCAM). Designed by Elisabeth Bock's group (University of Copenhagen) to replicate NCAM's interaction with fibroblast growth factor receptor 1 (FGFR1). Preclinical studies report that FGL crosses the blood-brain barrier, activates FGFR1, promotes hippocampal neurogenesis, reduces amyloid-β induced neurotoxicity, and improves spatial learning in rodent models. No human clinical data. Research-chemical only.", "sequence": "Glu-Val-Tyr-Val-Val-Ala-Glu-Asn-Gln-Gln-Gly-Lys-Ser-Lys-Ala", "molecularFormula": "C73H118N20O23", "molecularWeight": 1659.85, "halfLife": { "value": null, "unit": null, "range": "Not characterized in humans", "notes": "Reported to cross the blood-brain barrier in rodents after peripheral (SC or IP) administration; no formal human pharmacokinetics." }, "fdaStatus": "research-only", "approvalDetails": "Not FDA-approved. No registered human clinical trials. Circulates in the research-chemical grey market as a putative nootropic; any human use would be unapproved and unsupported by human safety data.", "mechanism": "Mimics a FGFR1-binding motif within the NCAM F3 module. Engages FGFR1 at the cell surface, triggering dimerization and autophosphorylation with downstream activation of the PLCγ, MAPK/ERK, and PI3K/Akt pathways. In preclinical studies this has been associated with increased adult hippocampal neurogenesis (as measured by BrdU incorporation in the dentate gyrus), reduced amyloid-β-induced hippocampal cell death, and improved performance in Morris water maze and fear conditioning paradigms. Mechanism is preclinically characterized but has never been validated clinically.", "primaryUses": [ "Cognitive enhancement research (preclinical only)", "Alzheimer disease models (rodent)", "Post-stroke neurogenesis research (rodent)" ], "typicalDose": { "range": "Not established for human use", "unit": null, "frequency": null, "route": null, "notes": "⚠ No human dosing established. Rodent studies commonly used 1–10 mg/kg subcutaneous or intranasal. Any human use would be entirely unregulated and unsupported by clinical evidence." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Neiiendam JL, et al. \"An NCAM-derived FGF-receptor agonist, the FGL-peptide, induces neurite outgrowth and neuronal survival in primary rat neurons.\" J Neurochem, 2004;91:920-935. PMID: 15525346.", "pmid": "15525346" }, { "type": "pubmed", "citation": "Knafo S, et al. \"The NCAM-derived peptide FGL facilitates the intermediate stage of synaptic consolidation and the induction of LTP in the rat hippocampal CA1.\" J Neurosci, 2005;25:8459-8466." }, { "type": "pubmed", "citation": "Corbett NJ, et al. \"FGL-peptide, an NCAM-derived agonist of FGFR1, reduces tau phosphorylation in rat hippocampus.\" PLoS One, 2013;8:e56047." } ], "interactionCoverage": "unreviewed", "related": [ "dihexa", "p21", "davunetide" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "fk-13", "name": "FK-13", "aliases": [ "LL-37(17-29)", "FKRIVQRIKDFLR", "LL-37 central fragment" ], "tier": "stub", "category": "healing", "subcategory": "LL-37-derived antimicrobial peptide fragment", "class": "A 13-amino-acid synthetic fragment of the human cathelicidin LL-37, spanning residues 17–29, which retains antimicrobial and immunomodulatory activity with a smaller size and different selectivity profile than the parent peptide.", "tagline": "The 13-residue FKRIVQRIKDFLR central fragment of LL-37 — the smallest LL-37 fragment that retains broad-spectrum antimicrobial activity while losing much of the parent peptide's cytotoxicity toward mammalian cells. Research-only; no clinical development program.", "oneLiner": "A 13-residue peptide corresponding to LL-37 residues 17–29 (Phe-Lys-Arg-Ile-Val-Gln-Arg-Ile-Lys-Asp-Phe-Leu-Arg). Characterized as a minimal fragment retaining the core antimicrobial activity of the parent cathelicidin LL-37 while substantially reducing cytotoxicity toward host cells. Widely used as a research tool for dissecting the structure-activity relationship of LL-37 and as a template for developing LL-37-derived antimicrobial peptide therapeutics. Not in clinical development as a therapeutic; not FDA-approved.", "sequence": "Phe-Lys-Arg-Ile-Val-Gln-Arg-Ile-Lys-Asp-Phe-Leu-Arg", "molecularFormula": "C76H128N22O17", "molecularWeight": 1645.99, "halfLife": { "value": null, "unit": null, "range": "Not formally characterized in vivo", "notes": "Short plasma half-life typical of cationic antimicrobial peptides (minutes); susceptible to serum proteases." }, "fdaStatus": "research-only", "approvalDetails": "Not FDA-approved. Not in any registered clinical trial. Research peptide only, available from peptide-synthesis vendors.", "mechanism": "Forms amphipathic α-helical conformation on membrane contact, with cationic residues (arginines and lysines) binding negatively charged phospholipid headgroups of bacterial membranes and hydrophobic residues partitioning into the lipid bilayer. Causes membrane disruption at high concentrations and likely secondary effects on intracellular targets. The central fragment retains this membrane-targeting mechanism of the parent LL-37 while lacking the N-terminal and C-terminal regions that contribute to LL-37's cytotoxicity on mammalian cells; this shifts the therapeutic index toward bacterial selectivity. Also retains chemotactic activity on neutrophils and monocytes.", "primaryUses": [ "Antimicrobial peptide research (in vitro and in vivo microbiology)", "LL-37 structure-activity research", "Template for AMP drug discovery" ], "typicalDose": { "range": "Not established for human use", "unit": null, "frequency": null, "route": null, "notes": "⚠ No human dosing established. Any human use would be entirely unregulated and unsupported by any clinical evidence." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "Li X, et al. \"Solution structures of human LL-37 fragments and NMR-based identification of a minimal membrane-targeting antimicrobial and anticancer region.\" J Am Chem Soc, 2006;128:5776-5785. PMID: 16637646.", "pmid": "16637646" }, { "type": "pubmed", "citation": "Wang G. \"Structures of human host defense cathelicidin LL-37 and its smallest antimicrobial peptide KR-12 in lipid micelles.\" J Biol Chem, 2008;283:32637-32643. PMID: 18818205.", "pmid": "18818205" }, { "type": "review", "citation": "Kościuczuk EM, et al. \"Cathelicidins: family of antimicrobial peptides. A review.\" Mol Biol Rep, 2012;39:10957-10970. PMID: 23065264.", "pmid": "23065264" } ], "interactionCoverage": "unreviewed", "related": [ "ll-37", "kr-12" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "follistatin-315", "name": "Follistatin-315", "aliases": [ "FS-315", "Follistatin 315" ], "tier": "stub", "category": "research", "subcategory": "myostatin inhibitor (activin/TGF-β family)", "class": "The shorter (315-amino-acid) splice variant of follistatin, lacking the C-terminal acidic tail present in FS-344.", "tagline": "The dominant circulating follistatin isoform in human serum — binds heparan sulfate proteoglycans avidly, concentrating at tissue surfaces rather than circulating freely, which limits its systemic reach compared to FS-344.", "oneLiner": "The 315-residue splice variant of follistatin, distinguished from FS-344 by the absence of the C-terminal 29-residue acidic tail, which gives FS-315 higher affinity for cell-surface heparan sulfate proteoglycans and therefore a more tissue-bound distribution pattern.", "sequence": null, "molecularFormula": null, "molecularWeight": 34829, "halfLife": { "value": null, "unit": null, "range": "minutes (circulating); tissue-bound component is long-lived", "notes": "Cell-surface binding dominates the pharmacokinetics — most injected FS-315 is rapidly sequestered at tissues near the injection site." }, "fdaStatus": "preclinical", "approvalDetails": "Not approved. Less-studied clinically than FS-344 precisely because its tissue-binding profile limits systemic efficacy. Used primarily as a research tool and in some community preparations sold alongside or instead of FS-344.", "mechanism": "Same ligand-binding specificity as FS-344 — neutralizes myostatin, activin A, and related TGF-β superfamily members. Functional differences between the two isoforms arise from distribution rather than intrinsic binding activity: FS-315's heparan sulfate affinity concentrates it at tissue surfaces, producing more local and less systemic effect when administered peripherally.", "primaryUses": [ "Muscle biology research", "Activin/reproductive biology research", "Community use (often sold interchangeably with FS-344, despite pharmacological differences)" ], "typicalDose": { "range": "research-only", "unit": "", "frequency": "varies", "route": "intramuscular or subcutaneous (community)", "notes": "No validated human dosing. Community sourcing typically does not verify which isoform is actually supplied." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Sugino K, et al. \"Molecular heterogeneity of follistatin, an activin-binding protein: higher affinity of the carboxyl-terminal truncated forms for heparan sulfate proteoglycans on the ovarian granulosa cell.\" J Biol Chem, 1993;268:15579-15587. PMID: 8340384.", "pmid": "8340384" }, { "type": "pubmed", "citation": "Schneyer A, et al. \"Differential distribution of follistatin isoforms: application of a new FS315-specific immunoassay.\" J Clin Endocrinol Metab, 2004;89:5067-5075. PMID: 15472207.", "pmid": "15472207" } ], "interactionCoverage": "unreviewed", "related": [ "follistatin-344", "ace-031", "peg-mgf" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S4.3", "named": true, "wording": "e.g. follistatin, myostatin propeptide", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Named as an example of the myostatin-binding proteins." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S4.3", "named": true, "wording": "e.g. follistatin, myostatin propeptide", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Named as an example of the myostatin-binding proteins." } ], "moleculeClass": "protein", "moleculeClassBasis": "315-amino-acid" }, { "id": "follistatin-344", "name": "Follistatin-344", "aliases": [ "FS-344", "Follistatin 344" ], "tier": "mid", "category": "research", "subcategory": "myostatin inhibitor (activin/TGF-β family)", "class": "A 344-amino-acid splice variant of the follistatin protein that binds and neutralizes myostatin, activin A, and related TGF-β family ligands.", "tagline": "The myostatin blocker tested only as gene therapy in six men, sold online in vials that often do not contain it.", "oneLiner": "A 344-amino-acid follistatin isoform that blocks myostatin; its only human study delivered the gene, not the protein.", "sequence": null, "molecularFormula": null, "molecularWeight": 37871, "halfLife": { "value": null, "unit": null, "range": "protein; tissue-bound", "notes": "Native follistatin is heparin-binding and largely tissue-resident; circulating half-life is short. Injected recombinant FS-344 has limited pharmacokinetic data.", "source": { "type": "qualitative", "note": "a description with no figure; no half-life measurement is cited for it" } }, "fdaStatus": "preclinical", "approvalDetails": "Not approved anywhere and no pharmaceutical formulation exists. The only study in people delivered the FS344 gene by AAV1 injection into the quadriceps of six men with Becker muscular dystrophy.", "mechanism": "Binds and inactivates myostatin (a negative regulator of muscle mass), activin A, and other TGF-β family ligands. Myostatin-null mammals — including the famous double-muscled Belgian Blue cattle and rare human mutation carriers — exhibit dramatic skeletal muscle hypertrophy, establishing the therapeutic rationale. Injected or gene-therapy-delivered follistatin phenocopies part of this effect in animal models.", "primaryUses": [ "Becker muscular dystrophy (gene therapy, phase 1/2a)" ], "typicalDose": { "range": "research-only", "unit": "", "frequency": "varies", "route": "intramuscular or subcutaneous (community)", "notes": "No established human dosing for injected recombinant protein. Gene therapy dosing (AAV1 viral titers) is not comparable to peptide injection." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Mendell JR, et al. \"A phase 1/2a follistatin gene therapy trial for becker muscular dystrophy.\" Mol Ther, 2015;23(1):192-201. PMID: 25322757.", "pmid": "25322757" }, { "type": "pubmed", "citation": "Reichel C, et al. \"Detection of black market follistatin 344.\" Drug Test Anal, 2019;11(11-12):1675-1697. PMID: 31758732.", "pmid": "31758732" }, { "type": "pubmed", "citation": "Perakakis N, et al. \"Follistatins in glucose regulation in healthy and obese individuals.\" Diabetes Obes Metab, 2019;21(3):683-690. PMID: 30393997.", "pmid": "30393997" }, { "type": "pubmed", "citation": "Lee SJ. \"Regulation of muscle mass by myostatin.\" Annu Rev Cell Dev Biol, 2004;20:61-86. PMID: 15473835.", "pmid": "15473835" }, { "type": "clinicaltrials", "citation": "ClinicalTrials.gov NCT01519349: follistatin gene transfer to patients with Becker muscular dystrophy and sporadic inclusion body myositis, completed (registry record read September 30, 2026)." } ], "interactionCoverage": "none-found", "related": [ "follistatin-315", "ace-031", "peg-mgf", "igf-1-lr3" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S4.3", "named": true, "wording": "e.g. follistatin, myostatin propeptide", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Named as an example of the myostatin-binding proteins." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S4.3", "named": true, "wording": "e.g. follistatin, myostatin propeptide", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Named as an example of the myostatin-binding proteins." } ], "moleculeClass": "protein", "moleculeClassBasis": "344-amino-acid" }, { "id": "follitropin-alfa", "name": "Follitropin alfa", "aliases": [ "Gonal-f", "Gonal-F RFF", "Gonal-F RFF Redi-ject", "rFSH alfa" ], "tier": "full", "category": "sexual-health", "subcategory": "recombinant FSH", "class": "Recombinant human follicle-stimulating hormone produced in Chinese hamster ovary (CHO) cells — a heterodimeric glycoprotein identical in amino acid sequence to native pituitary FSH.", "tagline": "Recombinant human FSH (Gonal-f), approved in the US on September 29, 1997, the same day as follitropin beta: daily injections that grow ovarian follicles for ovulation induction and IVF and, with hCG, restart sperm production in men with hypogonadotropic hypogonadism.", "oneLiner": "Recombinant human follicle-stimulating hormone made in Chinese hamster ovary cells: a 92-amino-acid alpha and a 111-amino-acid beta subunit, structurally indistinguishable from human FSH, about 31 kDa (label). Dosed daily in international units, 75 to 450 IU, under fertility-specialist monitoring.", "sequence": null, "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": 42.6, "unit": "hours", "range": "42.6 h after one subcutaneous injection in healthy women (2016); 24 to 41 h across the label's studies", "notes": "Elimination after subcutaneous injection depends on the absorption rate, which falls as body-mass index rises (label)." }, "fdaStatus": "approved", "approvalDetails": "FDA-approved as Gonal-f (EMD Serono), BLA 020378, on September 29, 1997, the same day as Organon's follitropin beta (Follistim, BLA 020582); Gonal-f RFF Redi-ject pen, BLA 021684, approved May 25, 2004 (Drugs@FDA, read September 28, 2026). Vial label: ovulation induction in oligo-anovulatory women whose infertility is functional and not due to primary ovarian failure; multiple-follicle development in ovulatory women during assisted reproduction; induction of spermatogenesis in men with primary or secondary hypogonadotropic hypogonadism. The pen is labelled for the two uses in women.", "mechanism": "Binds FSH receptor (FSHR) on ovarian granulosa cells (supporting follicle growth, estradiol synthesis, and granulosa-cell proliferation) and on testicular Sertoli cells (supporting spermatogenesis). In women, FSHR activation drives follicular recruitment and growth in the early-to-mid follicular phase; in men with hypogonadotropic hypogonadism, it supports seminiferous tubule maturation and sperm production.", "primaryUses": [ "Anovulatory infertility (non-primary-ovarian-failure)", "Controlled ovarian stimulation in IVF/ICSI", "Induction of spermatogenesis in male hypogonadotropic hypogonadism (co-administered with hCG)" ], "typicalDose": { "range": "75–450", "unit": "IU/day", "frequency": "daily (women); three times weekly (men)", "route": "subcutaneous", "notes": "Ovulation induction: 75 IU a day for 14 days in the first cycle, then individualised, maximum 300 IU a day. Assisted reproduction: 150 IU a day, adjusted after 3 to 5 days by 75 to 150 IU, maximum 450 IU a day. Men: hCG alone for 3 to 6 months until testosterone is normal, then 150 IU three times a week with hCG (label)." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Gonal-f (follitropin alfa) for injection and Gonal-f RFF Redi-ject (follitropin alfa) injection Prescribing Information. EMD Serono (DailyMed versions published 2025-09-05 and 2025-04-07, read 2026-09-28)." }, { "type": "fda-pi", "citation": "US FDA, Drugs@FDA: Gonal-f, BLA 020378, approved 1997-09-29; Gonal-f RFF Redi-ject, BLA 021684, approved 2004-05-25 (EMD Serono); Follistim (follitropin beta), BLA 020582, approved 1997-09-29 (Organon) (read 2026-09-28)." }, { "type": "pubmed", "citation": "Strowitzki T, et al. \"Ovarian stimulation in women undergoing in-vitro fertilization and embryo transfer using recombinant human follicle stimulating hormone (Gonal-F) in non-down-regulated cycles.\" Hum Reprod, 1995;10(12):3097-101. PMID: 8822421.", "pmid": "8822421" }, { "type": "pubmed", "citation": "Liu PY, et al. \"Efficacy and safety of recombinant human follicle stimulating hormone (Gonal-F) with urinary human chorionic gonadotrophin for induction of spermatogenesis and fertility in gonadotrophin-deficient men.\" Hum Reprod, 1999;14(6):1540-5. PMID: 10357972.", "pmid": "10357972" }, { "type": "pubmed", "citation": "Yong PY, et al. \"A prospective randomized clinical trial comparing 150 IU and 225 IU of recombinant follicle-stimulating hormone (Gonal-F*) in a fixed-dose regimen for controlled ovarian stimulation in in vitro fertilization treatment.\" Fertil Steril, 2003;79(2):308-15. PMID: 12568839.", "pmid": "12568839" }, { "type": "pubmed", "citation": "Moon SY, et al. \"Comparison of the efficacy and safety of a new recombinant human follicle-stimulating hormone (DA-3801) with follitropin-alpha (Gonal-F) in women undergoing controlled ovarian hyperstimulation for assisted reproductive technology.\" J Obstet Gynaecol Res, 2007;33(3):305-15. PMID: 17578360.", "pmid": "17578360" }, { "type": "pubmed", "citation": "Matsumoto AM, et al. \"Stimulation of spermatogenesis with recombinant human follicle-stimulating hormone (follitropin alfa; GONAL-f): long-term treatment in azoospermic men with hypogonadotropic hypogonadism.\" Fertil Steril, 2009;92(3):979-990. PMID: 18930190.", "pmid": "18930190" }, { "type": "pubmed", "citation": "Wolzt M, et al. \"Comparison of pharmacokinetic and safety profiles between Bemfola(®) and Gonal-f(®) after subcutaneous application.\" Eur J Drug Metab Pharmacokinet, 2016;41(3):259-65. PMID: 25633239.", "pmid": "25633239" }, { "type": "pubmed", "citation": "Humaidan P, et al. \"Efficacy and safety of follitropin alfa/lutropin alfa in ART: a randomized controlled trial in poor ovarian responders.\" Hum Reprod, 2017;32(3):544-555. PMID: 28137754.", "pmid": "28137754" }, { "type": "pubmed", "citation": "Alcalá-Sánchez X, et al. \"Comparison of DNA damage in granulosa cells of women undergoing controlled ovarian stimulation in in vitro fertilization protocols with the recombinant human follicle-stimulating hormones Corneumon(®), Gonal-F(®), Pergoveris(®) and Puregon(®): a randomized trial.\" Arch Gynecol Obstet, 2024;309(5):2107-2114. PMID: 38441601.", "pmid": "38441601" }, { "type": "pubmed", "citation": "Bernabeu A, et al. \"Ovarian stimulation with follitropin delta for in vitro fertilization: a multicentre, randomized, assessor-blind comparison with follitropin alfa using conventional dosing regimens (ADAPT-1 trial).\" Hum Reprod, 2025;40(9):1660-1670. PMID: 40633120.", "pmid": "40633120" } ], "interactionCoverage": "partial", "related": [ "follitropin-beta", "follitropin-delta", "urofollitropin", "menotropin", "hcg", "cetrorelix" ], "lastReviewed": "2026-09-28", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Follicle-stimulating hormone is not named, and S2.2.1's examples (CG, LH, GnRH agonists, kisspeptin) are testosterone-stimulating hormones, which FSH is not." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Follicle-stimulating hormone is not named, and S2.2.1's examples (CG, LH, GnRH agonists, kisspeptin) are testosterone-stimulating hormones, which FSH is not." } ], "moleculeClass": "protein", "moleculeClassBasis": "follicle-stimulating hormone" }, { "id": "follitropin-beta", "name": "Follitropin beta", "aliases": [ "Follistim", "Follistim AQ", "Puregon", "rFSH beta" ], "tier": "stub", "category": "sexual-health", "subcategory": "recombinant FSH", "class": "Recombinant human FSH produced in CHO cells — clinically equivalent to follitropin alfa with minor glycosylation and manufacturing differences.", "tagline": "Organon/Merck's Follistim AQ (Puregon internationally) — a recombinant human FSH produced independently of follitropin alfa but clinically equivalent; FDA-approved 1997 for ovulation induction and IVF controlled ovarian stimulation.", "oneLiner": "A recombinant human FSH produced in CHO cells, developed and marketed by Organon (now Merck/MSD). Amino acid sequence identical to endogenous FSH and to follitropin alfa; the two products differ only in expression-cell-line-specific glycosylation signatures, which are not clinically distinguishable in head-to-head trials. FDA-approved in 1997 under the brand name Follistim (later Follistim AQ, aqueous formulation); marketed internationally as Puregon.", "sequence": null, "molecularFormula": null, "molecularWeight": 30000, "halfLife": { "value": 40, "unit": "hours", "range": "~40 hours (SC, single dose); ~15 hours after repeat dosing", "notes": "Pharmacokinetics clinically equivalent to follitropin alfa." }, "fdaStatus": "approved", "approvalDetails": "FDA-approved as Follistim (follitropin beta, Organon/Merck, first approved September 1997); reformulated and relaunched as Follistim AQ (aqueous) and Follistim AQ Cartridge for use with the Follistim Pen delivery device. Indications: induction of ovulation in ovulatory-dysfunction infertility; development of multiple follicles in women undergoing assisted reproductive technologies.", "mechanism": "FSHR agonism on granulosa cells — identical in mechanism and clinical effect to follitropin alfa. Drives follicular recruitment and maturation during the controlled-ovarian-stimulation or ovulation-induction cycle.", "primaryUses": [ "Anovulatory infertility (non-primary-ovarian-failure)", "Controlled ovarian stimulation in IVF/ICSI" ], "typicalDose": { "range": "50–450", "unit": "IU/day", "frequency": "daily", "route": "subcutaneous", "notes": "Ovulation induction: 75 IU/day SC starting dose, titrated. IVF: 150–300 IU/day SC. Delivered via Follistim Pen cartridges of 300, 600, or 900 IU." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Follistim AQ (follitropin beta injection) Prescribing Information. Organon USA / Merck." }, { "type": "pubmed", "citation": "Al-Inany HG, et al. \"Recombinant versus urinary human chorionic gonadotrophin for ovulation induction in assisted conception.\" Cochrane Database Syst Rev, 2005;(2):CD003719 (systematic-review context for rFSH equivalence). PMID: 15846677.", "pmid": "15846677" } ], "interactionCoverage": "partial", "related": [ "follitropin-alfa", "follitropin-delta", "urofollitropin", "menotropin", "hcg", "ganirelix" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Follicle-stimulating hormone is not named, and S2.2.1's examples (CG, LH, GnRH agonists, kisspeptin) are testosterone-stimulating hormones, which FSH is not." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Follicle-stimulating hormone is not named, and S2.2.1's examples (CG, LH, GnRH agonists, kisspeptin) are testosterone-stimulating hormones, which FSH is not." } ], "moleculeClass": "protein", "moleculeClassBasis": "Recombinant human FSH" }, { "id": "follitropin-delta", "name": "Follitropin delta", "aliases": [ "Rekovelle", "FE 999049" ], "tier": "stub", "category": "sexual-health", "subcategory": "recombinant FSH", "class": "Recombinant human FSH produced in a human (PER.C6) cell line — approved internationally with an algorithmic AMH + body-weight-based dosing regimen; not FDA-approved in the US.", "tagline": "Ferring's Rekovelle — a recombinant human FSH produced in a human cell line (PER.C6), dosed via a personalized algorithm based on serum AMH and body weight. Approved in the EU, UK, Canada, Australia, Japan, and China, but received an FDA Complete Response Letter in February 2026 over manufacturing issues; not currently approved in the United States.", "oneLiner": "A recombinant human FSH manufactured in a human-derived PER.C6 cell line — the first rFSH with human-pattern glycosylation. Approved by the EMA as Rekovelle in December 2016 and subsequently in Canada, Australia, Switzerland, Japan, and China, with a novel individualized dosing algorithm based on serum anti-Müllerian hormone (AMH) and body weight (12 mcg/day fixed dose if AMH <15 pmol/L; 0.10–0.19 mcg/kg/day if AMH ≥15 pmol/L). Ferring received an FDA Complete Response Letter in February 2026 related to the Catalent Indiana manufacturing site; not currently approved in the United States.", "sequence": null, "molecularFormula": null, "molecularWeight": 30000, "halfLife": { "value": 40, "unit": "hours", "range": "~28–40 hours", "notes": "Pharmacokinetics broadly similar to follitropin alfa; the human-cell-line glycosylation produces a modestly different receptor signaling profile reported to enhance ovarian response at lower microgram doses." }, "fdaStatus": "not-approved-us", "approvalDetails": "EMA-approved as Rekovelle (Ferring Pharmaceuticals, December 2016) for controlled ovarian stimulation in women undergoing IVF/ICSI. Approved in the United Kingdom, Canada, Australia, Switzerland, Japan (2023), and China (April 2024). Received an FDA Complete Response Letter in February 2026 citing manufacturing concerns at the Catalent Indiana fill-finish site; not currently approved in the United States. Ferring has stated intent to address the manufacturing findings and re-file.", "mechanism": "FSHR agonism equivalent to follitropin alfa/beta. The human-cell-line glycosylation confers modestly increased FSH-receptor affinity and a different bioavailability-to-dose ratio, which underpins the microgram-based (rather than IU-based) dosing convention unique to this product.", "primaryUses": [ "Controlled ovarian stimulation for IVF/ICSI (ex-US)" ], "typicalDose": { "range": "6–12 (individualized)", "unit": "mcg/day", "frequency": "daily", "route": "subcutaneous (pre-filled pen)", "notes": "Individualized algorithm: if AMH <15 pmol/L, fixed dose 12 mcg/day for the first cycle; if AMH ≥15 pmol/L, 0.10–0.19 mcg/kg/day (rounded to nearest 0.33 mcg, maximum 12 mcg/day). Subsequent cycles adjusted based on response. Note: doses are expressed in micrograms of protein, not IU, and are not interchangeable IU-for-IU with other rFSH products." }, "evidenceLevel": "high", "sources": [ { "type": "other", "citation": "Rekovelle (follitropin delta) Summary of Product Characteristics. European Medicines Agency." }, { "type": "pubmed", "citation": "Nyboe Andersen A, et al. \"Individualized versus conventional ovarian stimulation for in vitro fertilization: a multicenter, randomized, controlled, assessor-blinded, phase 3 noninferiority trial.\" Fertil Steril, 2017;107:387-396 (ESTHER-1 pivotal). PMID: 27912901.", "pmid": "27912901" }, { "type": "other", "citation": "FDA Complete Response Letter to Ferring Pharmaceuticals regarding follitropin delta NDA, February 2026 (manufacturing findings at Catalent Indiana)." } ], "interactionCoverage": "none-found", "related": [ "follitropin-alfa", "follitropin-beta", "urofollitropin", "menotropin", "corifollitropin-alfa", "hcg" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": "EU (EMA), UK, Canada, Australia, Switzerland, Japan, China", "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Follicle-stimulating hormone is not named, and S2.2.1's examples (CG, LH, GnRH agonists, kisspeptin) are testosterone-stimulating hormones, which FSH is not." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Follicle-stimulating hormone is not named, and S2.2.1's examples (CG, LH, GnRH agonists, kisspeptin) are testosterone-stimulating hormones, which FSH is not." } ], "moleculeClass": "protein", "moleculeClassBasis": "Recombinant human FSH" }, { "id": "foxo4-dri", "name": "FOXO4-DRI", "aliases": [ "FOXO4-p53 interfering peptide", "FOXO4 DRI" ], "tier": "stub", "category": "longevity", "subcategory": "senolytic peptide", "class": "A D-retro-inverso (DRI) peptide designed to disrupt the FOXO4-p53 protein-protein interaction selectively in senescent cells.", "tagline": "A senolytic peptide that clears senescent cells in mice and cultured cells, and has never been given to a person.", "oneLiner": "A mirror-image peptide that separates FOXO4 from p53 inside senescent cells so they die, tested only in animals and cells.", "sequence": "D-retro-inverso of LTLRKEPASEIAQSILEAY (with Antp import sequence)", "molecularFormula": "C228H388N86O64", "molecularWeight": 5358.0, "halfLife": { "value": null, "unit": null, "range": "undetermined in humans", "notes": "D-amino acid retro-inverso design confers resistance to protease degradation." }, "fdaStatus": "preclinical", "approvalDetails": "Not approved anywhere and never trialled in people. No application appears in FDA's Drugs@FDA database and no clinical trial of the peptide is published or recruiting.", "mechanism": "Competitively inhibits the FOXO4-p53 protein-protein interaction that is specific to senescent cells. In senescent cells, this interaction sequesters p53 in the nucleus and prevents it from triggering apoptosis (part of the senescent phenotype). FOXO4-DRI disrupts this sequestration, freeing p53 to translocate to mitochondria and induce apoptosis specifically in p16-positive senescent cells — leaving non-senescent cells unaffected.", "primaryUses": [ "Senescent-cell clearance (preclinical)", "Ageing biology (mice and cell culture)" ], "typicalDose": { "range": "preclinical", "unit": "", "frequency": "intermittent", "route": "intraperitoneal (preclinical)", "notes": "No human dosing established. Community use carries substantial unknown risk given the pro-apoptotic mechanism." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Baar MP, et al. \"Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging.\" Cell, 2017;169(1):132-147.e16. PMID: 28340339.", "pmid": "28340339" }, { "type": "pubmed", "citation": "Bourgeois B, et al. \"The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI.\" Nat Commun, 2025;16(1):5672. PMID: 40593617.", "pmid": "40593617" }, { "type": "pubmed", "citation": "Huang Y, et al. \"Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells From in vitro Expanded Human Chondrocytes.\" Front Bioeng Biotechnol, 2021;9:677576. PMID: 33996787.", "pmid": "33996787" }, { "type": "pubmed", "citation": "Kong YX, et al. \"FOXO4-DRI induces keloid senescent fibroblast apoptosis by promoting nuclear exclusion of upregulated p53-serine 15 phosphorylation.\" Commun Biol, 2025;8(1):299. PMID: 39994346.", "pmid": "39994346" }, { "type": "pubmed", "citation": "Han X, et al. \"FOXO4 peptide targets myofibroblast ameliorates bleomycin-induced pulmonary fibrosis in mice through ECM-receptor interaction pathway.\" J Cell Mol Med, 2022;26(11):3269-3280. PMID: 35510614.", "pmid": "35510614" }, { "type": "pubmed", "citation": "Zhang C, et al. \"FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice.\" Aging (Albany NY), 2020;12(2):1272-1284. PMID: 31959736.", "pmid": "31959736" }, { "type": "pubmed", "citation": "Li Y, et al. \"FOXO4-DRI improves spermatogenesis in aged mice through reducing senescence-associated secretory phenotype secretion from Leydig cells.\" Exp Gerontol, 2024;195:112522. PMID: 39025385.", "pmid": "39025385" }, { "type": "other", "citation": "US FDA, Drugs@FDA (openFDA): no application for FOXO4-DRI. Read September 30, 2026." } ], "interactionCoverage": "unreviewed", "related": [ "epithalon", "ss-31", "humanin" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "galanin", "name": "Galanin", "aliases": [ "GAL", "Galanin-1-30" ], "tier": "stub", "category": "cognitive", "subcategory": "Endogenous neuropeptide", "class": "Galanin is a neuropeptide with unusually broad functions: it modulates pain, seizures, mood, appetite, memory, and neurogenesis through three receptor subtypes.", "tagline": "A neuropeptide with uniquely broad functions — modulating seizures, pain, mood, and neurogenesis across three receptor subtypes.", "oneLiner": "A 29/30-amino-acid neuropeptide widely expressed in the CNS and PNS that inhibits neurotransmitter release via GalR1-3 receptors, with roles in seizure suppression, nociception, mood regulation, and nerve regeneration after injury.", "sequence": "GWTLNSAGYLLGPHAVGNHRSFSDKNGLTS (human, 30 aa)", "molecularFormula": "C145H226N42O42S", "molecularWeight": 3163.6, "halfLife": { "value": 6, "unit": "minutes", "range": "4-8 minutes", "notes": "Short plasma half-life. Stable analogs (NAX 5055) developed for research." }, "fdaStatus": "research-only", "approvalDetails": "Not approved. GalR2 agonists are in preclinical development for epilepsy, depression, and neuropathic pain.", "mechanism": "Binds GalR1 (Gi-coupled, inhibitory — anticonvulsant/anxiolytic), GalR2 (Gq/Gi — neurotrophic, neurogenesis), GalR3 (Gi — anxiety/depression). Massively upregulated (10-100x) in dorsal root ganglia after nerve injury, promoting nerve regeneration.", "primaryUses": [ "Endogenous seizure suppression", "Nociception modulation", "Nerve regeneration after injury", "Research target for epilepsy gene therapy" ], "typicalDose": { "range": "N/A", "unit": "N/A", "frequency": "N/A", "route": "endogenous", "notes": "Not used as a drug. Stable analog NAX 5055 has shown anticonvulsant efficacy in rodent models." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "Tatemoto K, et al. \"Galanin -- a novel biologically active peptide from porcine intestine.\" FEBS Lett. 1983;164(1):124-128. PMID: 6197320.", "pmid": "6197320" }, { "type": "review", "citation": "Lang R, et al. \"Physiology, signaling, and pharmacology of galanin peptides and receptors.\" Pharmacol Rev. 2015;67(1):118-175. PMID: 25428932.", "pmid": "25428932" } ], "interactionCoverage": "unreviewed", "related": [ "neuropeptide-y", "neurotensin", "noopept", "selank" ], "lastReviewed": "2026-04-21", "publishedAt": "2026-04-21", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "ganirelix", "name": "Ganirelix", "aliases": [ "Ganirelix Acetate", "Orgalutran", "Antagon" ], "tier": "mid", "category": "sexual-health", "subcategory": "GnRH antagonist", "class": "Synthetic decapeptide GnRH-receptor antagonist approved for prevention of premature LH surges in IVF.", "tagline": "The GnRH antagonist that keeps an IVF cycle from ovulating early, and cut the protocol from weeks of injections to days.", "oneLiner": "A synthetic decapeptide that blocks the GnRH receptor directly, suppressing LH within hours instead of weeks.", "sequence": "Ac-D-Nal(2)-D-pClPhe-D-Pal(3)-Ser-Tyr-D-hArg(Et2)-Leu-hArg(Et2)-Pro-D-Ala-NH2", "molecularFormula": "C80H113ClN18O13", "molecularWeight": 1570.4, "halfLife": { "value": 12.8, "unit": "hours", "range": "12.8 hours after one dose, 16.2 hours with daily dosing", "source": { "type": "label", "ref": "Ganirelix Acetate Injection prescribing information, section 12.3 (DailyMed version 2, effective May 11, 2026; read September 30, 2026)" } }, "fdaStatus": "approved", "approvalDetails": "FDA-approved and still marketed, now only as generics: ganirelix acetate injection under ANDA 215658 (Gland), ANDA 216075 (Lupin) and ANDA 204246 (Sun, as Fyremadel). The branded Antagon and Orgalutran products are no longer on the US market. The label dose is 250 mcg subcutaneously once daily until the day of hCG.", "mechanism": "Immediate competitive blockade of pituitary GnRH receptors, suppressing LH and FSH secretion without initial flare. Daily 250 mcg SC dose provides sustained LH-surge prevention until hCG trigger.", "primaryUses": [ "Inhibition of premature LH surges in controlled ovarian hyperstimulation (US label)" ], "typicalDose": { "range": "250", "unit": "mcg", "frequency": "daily", "route": "subcutaneous (thigh or abdomen)", "notes": "Initiated on stimulation day 5 or 6 when adequate follicular development is present, or when estradiol rises rapidly. Continued daily through day of hCG administration." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Ganirelix Acetate Injection Prescribing Information, Indications and Dosage sections (DailyMed version 2, effective May 11, 2026; read September 30, 2026)." }, { "type": "pubmed", "citation": "Borm G, et al. \"Treatment with the gonadotrophin-releasing hormone antagonist ganirelix in women undergoing ovarian stimulation with recombinant follicle stimulating hormone is effective, safe and convenient: results of a controlled, randomized, multicentre trial. The European Orgalutran Study Group.\" Hum Reprod, 2000;15(7):1490-8. PMID: 10875855.", "pmid": "10875855" }, { "type": "pubmed", "citation": "Olivennes F, et al. \"Perinatal outcome of pregnancy after GnRH antagonist (ganirelix) treatment during ovarian stimulation for conventional IVF or ICSI: a preliminary report.\" Hum Reprod, 2001;16(8):1588-91. PMID: 11473947.", "pmid": "11473947" }, { "type": "pubmed", "citation": "Luo X, et al. \"Fixed versus flexible antagonist protocol in women with predicted high ovarian response except PCOS: a randomized controlled trial.\" BMC Pregnancy Childbirth, 2021;21(1):348. PMID: 33934703.", "pmid": "33934703" }, { "type": "pubmed", "citation": "Martinez-Salazar J, et al. \"GnRH antagonist ganirelix prevents premature luteinization in IUI cycles: rationale for its use.\" Reprod Biomed Online, 2009;19(2):156-61. PMID: 19712548.", "pmid": "19712548" }, { "type": "other", "citation": "US FDA, Drugs@FDA (openFDA): ganirelix acetate injection, ANDA 215658 (Gland), ANDA 216075 (Lupin), ANDA 204246 (Fyremadel, Sun), all prescription. Read September 30, 2026." } ], "interactionCoverage": "label", "related": [ "cetrorelix", "degarelix", "gonadorelin", "follitropin-alfa", "hcg" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "A GnRH antagonist: S2.2.1 covers GnRH and its agonist analogues, not antagonists." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "A GnRH antagonist: S2.2.1 covers GnRH and its agonist analogues, not antagonists." } ], "moleculeClass": "peptide" }, { "id": "garetosmab", "name": "Garetosmab", "aliases": [ "REGN2477" ], "tier": "mid", "category": "pipeline", "subcategory": "anti-activin A monoclonal antibody", "class": "A fully human monoclonal antibody against activin A, developed by Regeneron for fibrodysplasia ossificans progressiva (FOP).", "tagline": "An anti-activin A antibody approved in 2026 for fibrodysplasia ossificans progressiva, after a phase 2 that missed its primary endpoint.", "oneLiner": "A monoclonal antibody that removes activin A, the protein that switches on the mutated receptor turning soft tissue to bone.", "sequence": null, "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": "weeks", "range": "Fc-mediated; weeks", "notes": "Long half-life typical of full-length therapeutic antibodies.", "source": { "type": "qualitative", "note": "a description with no figure; no half-life measurement is cited for it" } }, "fdaStatus": "approved", "approvalDetails": "FDA-approved August 19, 2026 as Pasatru (garetosmab-grts), Regeneron, BLA 761508, to reduce new heterotopic ossification lesions and clinician-assessed flare-ups in adults with fibrodysplasia ossificans progressiva; 10 mg/kg intravenously every four weeks.", "mechanism": "Binds and neutralizes activin A, a TGF-β superfamily ligand that signals through ActRIIA. In FOP, activin A is a pathological driver of heterotopic ossification via the mutant ACVR1 receptor. Blocking activin A removes the aberrant osteogenic signal. The pathway overlap with bimagrumab (which blocks ActRII receptors) is indirect but pharmacologically related.", "primaryUses": [ "Fibrodysplasia ossificans progressiva in adults (US label)" ], "typicalDose": { "range": "not established", "unit": "mg/kg", "frequency": "monthly (trial protocols)", "route": "intravenous", "notes": "LUMINA-1 used fixed trial-protocol dosing." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "Di Rocco M, et al. \"Garetosmab in fibrodysplasia ossificans progressiva: a randomized, double-blind, placebo-controlled phase 2 trial.\" Nat Med, 2023;29(10):2615-2624. PMID: 37770652.", "pmid": "37770652" }, { "type": "pubmed", "citation": "Papa R, et al. \"Efficacy and safety of garetosmab, an activin A-blocking antibody, in fibrodysplasia ossificans progressiva (OPTIMA): a randomised, double-blind, placebo-controlled, phase 3 trial.\" Lancet, 2026. PMID: 42805227.", "pmid": "42805227" }, { "type": "pubmed", "citation": "Keen R, et al. \"Characterization of flare-ups and impact of garetosmab in adults with fibrodysplasia ossificans progressiva: a post hoc analysis of the randomized, double-blind, placebo-controlled LUMINA-1 trial.\" J Bone Miner Res, 2024;39(10):1486-1492. PMID: 39216107.", "pmid": "39216107" }, { "type": "pubmed", "citation": "Vanhoutte F, et al. \"Pharmacokinetics and Pharmacodynamics of Garetosmab (Anti-Activin A): Results From a First-in-Human Phase 1 Study.\" J Clin Pharmacol, 2020;60(11):1424-1431. PMID: 32557665.", "pmid": "32557665" }, { "type": "other", "citation": "US FDA, Drugs@FDA (openFDA): PASATRU (garetosmab-grts) injection, Regeneron, BLA 761508, approved August 19, 2026, prescription. Read September 30, 2026." }, { "type": "other", "citation": "US FDA, Novel Drug Approvals for 2026: Pasatru (garetosmab-grts), August 19, 2026; Atebrioz (zilurgisertib), September 25, 2026, for fibrodysplasia ossificans progressiva in patients 12 and older. Content current as of September 28, 2026; read September 30, 2026." }, { "type": "fda-pi", "citation": "Pasatru (garetosmab-grts) injection Prescribing Information, sections 1 and 2 (DailyMed version 1, effective August 14, 2026; read September 30, 2026)." } ], "interactionCoverage": "none-found", "related": [ "bimagrumab", "trevogrumab", "ace-031" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S4.3", "named": false, "wording": "Activin A-neutralizing antibodies", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "An anti-activin A antibody." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S4.3", "named": false, "wording": "Activin A-neutralizing antibodies", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "An anti-activin A antibody." } ], "moleculeClass": "antibody", "moleculeClassBasis": "monoclonal antibody" }, { "id": "gdf11", "name": "GDF11", "aliases": [ "Growth differentiation factor 11", "BMP-11" ], "tier": "stub", "category": "longevity", "subcategory": "TGF-β superfamily protein (parabiosis / aging research)", "class": "⚠ Protein, not a peptide — a ~12 kDa mature protein in the TGF-β superfamily, included here because of its prominence in the parabiosis / rejuvenation literature and frequent appearance in longevity grey-market discussion.", "tagline": "⚠ Not a peptide — a 12 kDa TGF-β superfamily protein. Rose to prominence through Amy Wagers' 2013–2014 parabiosis studies suggesting it was a \"youthful factor\" that could reverse cardiac, skeletal muscle, and neural aging in mice. Subsequent independent work substantially walked back or contradicted several of the original claims, and the current consensus view is that GDF11's role in aging is considerably more complex and less uniformly \"rejuvenating\" than early reports suggested.", "oneLiner": "A mature 109-amino-acid (~12 kDa) protein in the TGF-β superfamily that became central to rejuvenation research after a series of 2013–2014 papers from Amy Wagers' group and collaborators reported that restoring youthful GDF11 levels to old mice could reverse cardiac hypertrophy, improve skeletal muscle regeneration, and enhance hippocampal neurogenesis. Subsequent work from Novartis and other groups challenged both the assay specificity (GDF11 and the related myostatin/GDF8 cross-react in most commercial assays) and the phenotypic claims. The field has not converged on a unified view: GDF11 likely has context-dependent roles in tissue homeostasis and aging that were initially oversimplified. Included in the encyclopedia as a longevity-adjacent compound commonly discussed in aging and grey-market contexts, with the caveat that it is a protein rather than a short peptide and that the scientific consensus on its \"rejuvenating\" properties is contested.", "sequence": "109 amino acid mature protein (TGF-β superfamily); full-length prepro-GDF11 is 407 residues", "molecularFormula": null, "molecularWeight": 12700, "halfLife": { "value": null, "unit": null, "range": "Not formally characterized pharmacokinetically", "notes": "Endogenous circulating levels are picomolar. Commercial GDF11 ELISAs have significant cross-reactivity with myostatin (GDF8), which has complicated aging-related correlational studies." }, "fdaStatus": "research-only", "approvalDetails": "Not FDA-approved. Not in any registered human clinical trial. Research reagent only; available from recombinant-protein vendors.", "mechanism": "Binds the activin type II receptors (ActRIIA, ActRIIB) and the ALK4/5/7 type I receptors, activating SMAD2/3 signaling — the canonical TGF-β superfamily pathway shared with myostatin (GDF8). Because GDF11 and myostatin share very high sequence identity in their mature domains, their biological roles have been difficult to disentangle, and much of the controversy about \"GDF11 as a youthful factor\" traces to cross-reactivity issues in assays and to differences between in-vivo tissue context and in-vitro activity.", "primaryUses": [ "Aging and rejuvenation research (preclinical; contested)", "Cardiac hypertrophy research (preclinical)", "TGF-β superfamily biology" ], "typicalDose": { "range": "Not established for human use", "unit": null, "frequency": null, "route": null, "notes": "⚠ No human dosing established. Rodent rejuvenation studies used 0.1–1 mg/kg daily intraperitoneal recombinant GDF11. Any human use would be entirely unregulated and unsupported by any clinical evidence, and would raise substantial safety concerns given GDF11's myostatin-family signaling and potential effects on skeletal muscle mass and cardiovascular remodeling." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Loffredo FS, et al. \"Growth differentiation factor 11 is a circulating factor that reverses age-related cardiac hypertrophy.\" Cell, 2013;153:828-839 (original parabiosis paper). PMID: 23663781.", "pmid": "23663781" }, { "type": "pubmed", "citation": "Egerman MA, et al. \"GDF11 Increases with Age and Inhibits Skeletal Muscle Regeneration.\" Cell Metab, 2015;22:164-174 (Novartis counter-paper reporting opposite direction of effect). PMID: 26001423.", "pmid": "26001423" }, { "type": "pubmed", "citation": "Schafer MJ, et al. \"Quantification of GDF11 and Myostatin in Human Aging and Cardiovascular Disease.\" Cell Metab, 2016;23:1207-1215 (assay specificity critique). PMID: 27304512.", "pmid": "27304512" } ], "interactionCoverage": "unreviewed", "related": [ "humanin", "mots-c", "epithalon" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "protein", "moleculeClassBasis": "Protein, not a peptide" }, { "id": "gdf15", "name": "GDF15", "aliases": [ "Growth differentiation factor 15", "MIC-1", "NAG-1", "PLAB", "PTGFB" ], "tier": "mid", "category": "longevity", "subcategory": "TGF-β superfamily stress-response cytokine", "class": "⚠ Protein, not a peptide — a ~12 kDa TGF-β superfamily stress-response cytokine with a well-characterized role as a mitochondrial-stress biomarker, an anorexic / cachexia mediator, and an emerging therapeutic target in obesity and cachexia.", "tagline": "⚠ Not a peptide — a 12 kDa TGF-β superfamily protein. Rises with age and with mitochondrial stress; a potent anorexic/cachexia signal via its brainstem GFRAL/RET receptor. Active clinical development in two directions: agonism for obesity (NGM120, LY3463251) and antagonism for cachexia (ponsegromab, Pfizer Phase 3 PROACC-1 in cancer cachexia).", "oneLiner": "A 112-amino-acid mature protein (~12.5 kDa) in the TGF-β superfamily, secreted in response to cellular and mitochondrial stress. Uniquely among TGF-β family members, GDF15 signals through a non-canonical receptor — GDNF family receptor α-like (GFRAL) — expressed selectively in the area postrema and nucleus tractus solitarius of the hindbrain, which explains its striking and selective anorexic effects. Rises with aging and correlates with all-cause mortality; elevated in heart failure, cancer cachexia, and certain mitochondrial diseases. Has emerged as a drug target in two opposite directions: GDF15 analogs (e.g., NGM120, LY3463251) as anti-obesity agents, and GDF15 antagonists (ponsegromab / PF-06946860, Pfizer) as cachexia therapies — the Phase 3 PROACC-1 trial of ponsegromab in advanced cancer cachexia was ongoing as of early 2026. Not a short peptide — included here because of its prominence in aging-biomarker and metabolic grey-market discussion.", "sequence": "112 amino acid mature protein (TGF-β superfamily); full-length prepro-GDF15 is 308 residues", "molecularFormula": null, "molecularWeight": 12500, "halfLife": { "value": null, "unit": null, "range": "not reported in the sources read", "source": { "type": "none", "note": "searched PubMed on October 1, 2026; no human half-life figure for GDF15 itself in the sources read" } }, "fdaStatus": "clinical-trials", "approvalDetails": "Not approved; no application for GDF15 appears in Drugs@FDA (read October 1, 2026). Ponsegromab, a humanised antibody that blocks GDF15, completed a phase 2 trial in cancer cachexia and remains investigational.", "mechanism": "Signals through GFRAL (GDNF family receptor α-like) and the co-receptor RET, which are uniquely expressed in hindbrain area postrema and nucleus tractus solitarius neurons. Activation of these neurons produces potent appetite suppression and aversion-like behavior; this is the mechanism by which pathologically elevated GDF15 drives cachexia in cancer and chronic disease, and the mechanism being exploited therapeutically with GDF15 analogs for obesity. The restriction of GFRAL expression to hindbrain areas that lack a blood-brain barrier (circumventricular organs) means GDF15 can signal centrally without crossing the BBB, which simplifies pharmacology. GDF15 is also induced by many cellular stressors (mitochondrial dysfunction, ER stress, oxidative stress) and is considered a canonical \"mitokine.\"", "primaryUses": [ "Cancer cachexia research (ponsegromab Phase 3; antagonism)", "Obesity research (GDF15 agonists in early clinical development)", "Mitochondrial-disease biomarker", "Aging and all-cause-mortality biomarker (epidemiologic research)" ], "typicalDose": { "range": null, "unit": null, "frequency": null, "route": null, "notes": "GDF15 itself is not given to people. Ponsegromab, the antibody that blocks it, was given at 100, 200 or 400 mg subcutaneously every four weeks in its phase 2 trial." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Groarke JD, et al. \"Ponsegromab for the Treatment of Cancer Cachexia.\" N Engl J Med, 2024;391(24):2291-2303. PMID: 39282907.", "pmid": "39282907" }, { "type": "pubmed", "citation": "Crawford J, et al. \"A Phase Ib First-In-Patient Study Assessing the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Ponsegromab in Participants with Cancer and Cachexia.\" Clin Cancer Res, 2024;30(3):489-497. PMID: 37982848.", "pmid": "37982848" }, { "type": "pubmed", "citation": "Groarke JD, et al. \"Phase 2 study of the efficacy and safety of ponsegromab in patients with cancer cachexia: PROACC-1 study design.\" J Cachexia Sarcopenia Muscle, 2024;15(3):1054-1061. PMID: 38500292.", "pmid": "38500292" }, { "type": "pubmed", "citation": "Mullican SE, et al. \"GFRAL is the receptor for GDF15 and the ligand promotes weight loss in mice and nonhuman primates.\" Nat Med, 2017;23(10):1150-1157. PMID: 28846097.", "pmid": "28846097" }, { "type": "pubmed", "citation": "Wang D, et al. \"GDF15: emerging biology and therapeutic applications for obesity and cardiometabolic disease.\" Nat Rev Endocrinol, 2021;17(10):592-607. PMID: 34381196.", "pmid": "34381196" } ], "interactionCoverage": "studied", "related": [ "humanin", "mots-c", "shlp2" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." } ], "moleculeClass": "protein", "moleculeClassBasis": "Protein, not a peptide" }, { "id": "ghk-cu", "name": "GHK-Cu", "aliases": [ "Copper tripeptide-1", "Cu-GHK", "Glycyl-L-histidyl-L-lysine:copper(II)", "Prezatide copper acetate" ], "tier": "full", "category": "healing", "subcategory": "copper-binding tripeptide", "class": "A naturally occurring tripeptide (Gly-His-Lys) that binds copper(II) with high affinity, identified in human plasma in 1973.", "tagline": "A copper-binding tripeptide found in human plasma and sold widely in skin care; the evidence is mostly cell and animal work, with few trials in people.", "oneLiner": "A glycyl-L-histidyl-L-lysine:copper(II) complex identified in human plasma in the 1970s, whose serum levels fall with age. Used widely in skin care and sold for injection, it has been tested in people only as a cream.", "sequence": "Gly-His-Lys (+ Cu²⁺)", "molecularFormula": "C14H23CuN6O4", "molecularWeight": 402.92, "halfLife": { "value": null, "unit": null, "range": "undetermined (systemic)", "notes": "Systemic pharmacokinetics not well-characterized. Topical absorption is the most-studied route." }, "fdaStatus": "research-only", "approvalDetails": "Not approved as an injectable drug. Widely used as an ingredient in cosmetic topical formulations (Copper Peptide skincare). No FDA-approved indication for subcutaneous use.", "mechanism": "GHK-Cu upregulates expression of genes involved in tissue remodeling, collagen and glycosaminoglycan synthesis, and antioxidant defense. It modulates the expression of decorin, integrins, and fibroblast growth factors, and has been shown in genomic studies to reverse multiple age-related gene expression changes. The copper cofactor is essential for lysyl oxidase activity in collagen cross-linking.", "primaryUses": [ "Topical skin regeneration (cosmetic)", "Wound healing research", "Hair growth (topical formulations)", "Community injectable use for skin quality and recovery" ], "typicalDose": { "range": "1–2", "unit": "mg", "frequency": "daily (injectable, community)", "route": "subcutaneous (community); topical (cosmetic)", "notes": "Community injectable dosing is not clinically validated. Cosmetic topical concentrations typically 0.05–5%." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Miller TR, et al. \"Effects of topical copper tripeptide complex on CO2 laser-resurfaced skin.\" Arch Facial Plast Surg, 2006;8(4):252-9. PMID: 16847171.", "pmid": "16847171" }, { "type": "pubmed", "citation": "Bossak-Ahmad K, et al. \"Ternary Cu(2+) Complexes of Human Serum Albumin and Glycyl-l-histidyl-l-lysine.\" Inorg Chem, 2021;60(22):16927-16931. PMID: 34730942.", "pmid": "34730942" }, { "type": "pubmed", "citation": "Lau SJ, et al. \"The interaction of copper(II) and glycyl-L-histidyl-L-lysine, a growth-modulating tripeptide from plasma.\" Biochem J, 1981;199(3):649-56. PMID: 7340824.", "pmid": "7340824" }, { "type": "pubmed", "citation": "Maquart FX, et al. \"In vivo stimulation of connective tissue accumulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ in rat experimental wounds.\" J Clin Invest, 1993;92(5):2368-76. PMID: 8227353.", "pmid": "8227353" }, { "type": "pubmed", "citation": "Fu SC, et al. \"Tripeptide-copper complex GHK-Cu (II) transiently improved healing outcome in a rat model of ACL reconstruction.\" J Orthop Res, 2015;33(7):1024-33. PMID: 25731775.", "pmid": "25731775" }, { "type": "pubmed", "citation": "Ma WH, et al. \"Protective effects of GHK-Cu in bleomycin-induced pulmonary fibrosis via anti-oxidative stress and anti-inflammation pathways.\" Life Sci, 2020;241:117139. PMID: 31809714.", "pmid": "31809714" }, { "type": "pubmed", "citation": "Deng M, et al. \"Glycyl-l-histidyl-l-lysine-Cu(2+) rescues cigarette smoking-induced skeletal muscle dysfunction via a sirtuin 1-dependent pathway.\" J Cachexia Sarcopenia Muscle, 2023;14(3):1365-1380. PMID: 36905132.", "pmid": "36905132" }, { "type": "pubmed", "citation": "Tucker M, et al. \"Intranasal GHK peptide enhances resilience to cognitive decline in aging mice.\" bioRxiv, 2023. PMID: 38014118.", "pmid": "38014118" }, { "type": "review", "citation": "Dou Y, et al. \"The potential of GHK as an anti-aging peptide.\" Aging Pathobiol Ther, 2020;2(1):58-61. PMID: 35083444.", "pmid": "35083444" }, { "type": "review", "citation": "Pickart L. \"The human tri-peptide GHK and tissue remodeling.\" J Biomater Sci Polym Ed, 2008;19(8):969-88. PMID: 18644225.", "pmid": "18644225" }, { "type": "review", "citation": "Pickart L, et al. \"Regenerative and Protective Actions of the GHK-Cu Peptide in the Light of the New Gene Data.\" Int J Mol Sci, 2018;19(7). PMID: 29986520.", "pmid": "29986520" }, { "type": "review", "citation": "Pickart L, et al. \"GHK Peptide as a Natural Modulator of Multiple Cellular Pathways in Skin Regeneration.\" Biomed Res Int, 2015;2015:648108. PMID: 26236730.", "pmid": "26236730" }, { "type": "review", "citation": "Mortazavi SM, et al. \"Topically applied GHK as an anti-wrinkle peptide: Advantages, problems and prospective.\" Bioimpacts, 2025;15:30071. PMID: 39963574.", "pmid": "39963574" }, { "type": "review", "citation": "Ogórek K, et al. \"Are We Ready to Measure Skin Permeation of Modern Antiaging GHK-Cu Tripeptide Encapsulated in Liposomes?.\" Molecules, 2025;30(1). PMID: 39795193.", "pmid": "39795193" }, { "type": "pubmed", "citation": "Bishop JB, et al. \"A prospective randomized evaluator-blinded trial of two potential wound healing agents for the treatment of venous stasis ulcers.\" J Vasc Surg, 1992;16(2):251-7. PMID: 1495150.", "pmid": "1495150" }, { "type": "pubmed", "citation": "Cangul IT, et al. \"Evaluation of the effects of topical tripeptide-copper complex and zinc oxide on open-wound healing in rabbits.\" Vet Dermatol, 2006;17(6):417-23. PMID: 17083573.", "pmid": "17083573" }, { "type": "pubmed", "citation": "Buffoni F, et al. \"Effect of tripeptide-copper complexes on the process of skin wound healing and on cultured fibroblasts.\" Arch Int Pharmacodyn Ther, 1995;330(3):345-60. PMID: 8836453.", "pmid": "8836453" }, { "type": "pubmed", "citation": "Abdulghani AA, et al. \"Effects of topical creams containing vitamin C, a copper-binding peptide cream and melatonin compared with tretinoin on the ultrastructure of normal skin.\" Dis Mon, 1998;44:1-22." } ], "interactionCoverage": "unreviewed", "related": [ "bpc-157", "tb-500", "ahk-cu", "matrixyl", "argireline" ], "lastReviewed": "2026-09-26", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "ghrelin", "name": "Ghrelin", "aliases": [ "Lenomorelin", "Growth Hormone Releasing Peptide", "Hunger Hormone" ], "tier": "mid", "category": "growth-hormone", "subcategory": "endogenous peptide hormone", "class": "A 28-amino-acid peptide hormone produced primarily by ghrelinergic cells in the gastrointestinal tract, functioning as the endogenous ligand for the growth hormone secretagogue receptor (GHS-R1a).", "tagline": "The stomach's hunger hormone: infused, it made every volunteer eat more; it is not a medicine, but drugs that copy it are.", "oneLiner": "A 28-amino-acid octanoylated stomach hormone that stimulates appetite and growth hormone release through the ghrelin receptor.", "sequence": "GSSFLSPEHQRVQQRKESKKPPAKLQPR (Ser3-octanoylated)", "molecularFormula": "C149H249N47O42", "molecularWeight": 3370.9, "halfLife": { "value": null, "unit": null, "range": "not reported in the sources read", "source": { "type": "none", "note": "searched on September 30, 2026; no half-life reported in the sources read" } }, "fdaStatus": "research-only", "approvalDetails": "Not a medicine anywhere; no application appears in Drugs@FDA. Drugs acting on its receptor, such as anamorelin, are separate entries.", "mechanism": "Binds GHS-R1a (a constitutively active GPCR) to stimulate GH release from the anterior pituitary, increase appetite via hypothalamic NPY/AgRP neurons, modulate gastric motility, and influence glucose homeostasis. The unique octanoyl modification on Ser3 (catalyzed by GOAT enzyme) is required for GHS-R1a activation.", "primaryUses": [ "Research on appetite and growth hormone" ], "typicalDose": { "range": "1–5", "unit": "mcg/kg", "frequency": "IV infusion (research only)", "route": "intravenous", "notes": "Used in clinical research protocols only. No established therapeutic dosing." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Kojima M, et al. \"Ghrelin is a growth-hormone-releasing acylated peptide from stomach.\" Nature, 1999;402(6762):656-60. PMID: 10604470.", "pmid": "10604470" }, { "type": "pubmed", "citation": "Wren AM, et al. \"Ghrelin enhances appetite and increases food intake in humans.\" J Clin Endocrinol Metab, 2001;86(12):5992. PMID: 11739476.", "pmid": "11739476" }, { "type": "pubmed", "citation": "Spiegel K, et al. \"Brief communication: Sleep curtailment in healthy young men is associated with decreased leptin levels, elevated ghrelin levels, and increased hunger and appetite.\" Ann Intern Med, 2004;141(11):846-50. PMID: 15583226.", "pmid": "15583226" }, { "type": "pubmed", "citation": "Weigle DS, et al. \"A high-protein diet induces sustained reductions in appetite, ad libitum caloric intake, and body weight despite compensatory changes in diurnal plasma leptin and ghrelin concentrations.\" Am J Clin Nutr, 2005;82(1):41-8. PMID: 16002798.", "pmid": "16002798" }, { "type": "pubmed", "citation": "Arvat E, et al. \"Ghrelin and synthetic GH secretagogues.\" Best Pract Res Clin Endocrinol Metab, 2002;16(3):505-17. PMID: 12464231.", "pmid": "12464231" }, { "type": "pubmed", "citation": "Müller TD, et al. \"Ghrelin.\" Mol Metab, 2015;4(6):437-60. PMID: 26042199.", "pmid": "26042199" }, { "type": "other", "citation": "US FDA, Drugs@FDA (openFDA): no application for ghrelin. Read September 30, 2026." } ], "interactionCoverage": "unreviewed", "related": [ "mk-677", "ghrp-2", "ghrp-6", "hexarelin", "anamorelin" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-20", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.2.4", "named": true, "wording": "lenomorelin (ghrelin)", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.2.4", "named": true, "wording": "lenomorelin (ghrelin)", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "ghrp-2", "name": "GHRP-2", "aliases": [ "Pralmorelin", "KP-102", "Growth Hormone Releasing Peptide 2" ], "tier": "full", "category": "growth-hormone", "subcategory": "GHRP / ghrelin receptor agonist", "class": "Second-generation growth hormone-releasing peptide — a synthetic hexapeptide agonist at the ghrelin receptor.", "tagline": "The second-generation GHRP, approved only in Japan (as pralmorelin) for a one-dose growth hormone test: a reliable growth hormone releaser that also raises ACTH, cortisol and appetite, and was never approved as a treatment.", "oneLiner": "A synthetic hexapeptide ghrelin receptor agonist (D-Ala-D-β-Nal-Ala-Trp-D-Phe-Lys-NH2) that potently stimulates GH release, approved in Japan (as pralmorelin) for diagnostic evaluation of GH deficiency.", "sequence": "D-Ala-D-2-Nal-Ala-Trp-D-Phe-Lys-NH2", "molecularFormula": "C45H55N9O6", "molecularWeight": 818.0, "halfLife": { "value": null, "unit": null, "range": "not reported in humans in the abstracts we hold", "notes": "In rats, plasma levels fell rapidly in two phases and 80% of an IV dose was recovered unchanged in bile within an hour (2005); in people, growth hormone peaked within 60 minutes of a 100 µg IV dose (2007). The earlier half-life figures on this site (about 1 hour here, 20 to 30 minutes on the pralmorelin entry) had no source." }, "fdaStatus": "not-approved-us", "approvalDetails": "Approved in Japan only, as a diagnostic: pralmorelin (GHRP Kaken 100, Kaken Pharmaceutical), a single-dose intravenous test for growth hormone deficiency (NIH NCATS record); its validation study used 100 µg IV. Treatment development (short stature in Japan, growth hormone deficiency in the US) reached phase II and was not approved. Not FDA-approved: 503A Category 3 on FDA's list updated May 14, 2026, and 503B Category 2 since September 29, 2023.", "mechanism": "Agonist at the growth hormone secretagogue receptor (the ghrelin receptor) in the pituitary and hypothalamus. It releases growth hormone directly from the pituitary (still 4.5-fold in people with a mutated GHRH receptor) and needs the hypothalamus for its full effect; it adds to GHRH, synergistically after chronic dosing. It also releases ACTH and cortisol, the basis of a Japanese adrenal test, and increases food intake as ghrelin does.", "primaryUses": [ "Diagnostic test for adult growth hormone deficiency (Japan, approved)", "Tests of the adrenal axis and of TSH-secreting pituitary tumours (Japanese studies)", "Research on ghrelin-receptor physiology", "Misused in sport for a hoped-for growth effect (prohibited)" ], "typicalDose": { "range": "100 (diagnostic)", "unit": "mcg", "frequency": "once (diagnostic test)", "route": "intravenous", "notes": "The Japanese diagnostic validation used 100 µg IV once after an overnight fast. Research doses: 1 µg/kg IV bolus; 1 µg/kg/h infusion; 5–15 µg/kg intranasally 2–3 times a day in a 1997 short-stature study. No study supports repeated subcutaneous self-injection." }, "evidenceLevel": "medium", "sources": [ { "type": "other", "citation": "NIH NCATS Inxight Drugs: pralmorelin (GHRP Kaken 100), marketed by Kaken Pharmaceutical in Japan as a single-dose diagnostic for growth hormone deficiency (read 2026-09-28)." }, { "type": "fda-pi", "citation": "US FDA. Bulk Drug Substances Nominated for Use in Compounding Under Section 503A (updated May 14, 2026): GHRP-2 in Category 3, nominated without adequate support." }, { "type": "fda-pi", "citation": "US FDA. Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks (current as of April 22, 2026): GHRP-2 in 503B Category 2 since September 29, 2023." }, { "type": "Human", "citation": "Bowers CY, et al. \"GHRP-2, GHRH and SRIF interrelationships during chronic administration of GHRP-2 to humans.\" J Pediatr Endocrinol Metab, 1996;9 Suppl 3:261-70. PMID: 8887169.", "pmid": "8887169" }, { "type": "Human", "citation": "Van den Berghe G, et al. \"The combined administration of GH-releasing peptide-2 (GHRP-2), TRH and GnRH to men with prolonged critical illness evokes superior endocrine and metabolic effects compared to treatment with GHRP-2 alone.\" Clin Endocrinol (Oxf), 2002;56(5):655-69. PMID: 12030918.", "pmid": "12030918" }, { "type": "Human", "citation": "Wideman L, et al. \"Synergy of L-arginine and GHRP-2 stimulation of growth hormone in men and women: modulation by exercise.\" Am J Physiol Regul Integr Comp Physiol, 2000;279(4):R1467-77. PMID: 11004017.", "pmid": "11004017" }, { "type": "Human", "citation": "Arimura H, et al. \"Investigation of the clinical significance of the growth hormone-releasing peptide-2 test for the diagnosis of secondary adrenal failure.\" Endocr J, 2016;63(6):533-44. PMID: 27020037.", "pmid": "27020037" }, { "type": "Human", "citation": "Chihara K, et al. \"A simple diagnostic test using GH-releasing peptide-2 in adult GH deficiency.\" Eur J Endocrinol, 2007;157(1):19-27. PMID: 17609397.", "pmid": "17609397" }, { "type": "Human", "citation": "Veldhuis JD, et al. \"Factors other than sex steroids modulate GHRH and GHRP-2 efficacies in men: evaluation using a GnRH agonist/testosterone clamp.\" J Clin Endocrinol Metab, 2009;94(7):2544-50. PMID: 19351731.", "pmid": "19351731" }, { "type": "Human", "citation": "Laferrère B, et al. \"Growth hormone releasing peptide-2 (GHRP-2), like ghrelin, increases food intake in healthy men.\" J Clin Endocrinol Metab, 2005;90(2):611-4. PMID: 15699539.", "pmid": "15699539" }, { "type": "Human", "citation": "Okano M, et al. \"Determination of growth hormone secretagogue pralmorelin (GHRP-2) and its metabolite in human urine by liquid chromatography/electrospray ionization tandem mass spectrometry.\" Rapid Commun Mass Spectrom, 2010;24(14):2046-56. PMID: 20552695.", "pmid": "20552695" }, { "type": "Human", "citation": "Okano M, et al. \"Influence of intravenous administration of growth hormone releasing peptide-2 (GHRP-2) on detection of growth hormone doping: growth hormone isoform profiles in Japanese male subjects.\" Drug Test Anal, 2010;2(11-12):548-56. PMID: 21249726.", "pmid": "21249726" }, { "type": "Human", "citation": "Kageyama K, et al. \"Evaluation of growth hormone-releasing peptide-2 for diagnosis of thyrotropin-producing pituitary adenomas.\" Endocr J, 2018;65(10):1049-1054. PMID: 29973439.", "pmid": "29973439" }, { "type": "Human", "citation": "Pihoker C, et al. \"Treatment effects of intranasal growth hormone releasing peptide-2 in children with short stature.\" J Endocrinol, 1997;155(1):79-86. PMID: 9390009.", "pmid": "9390009" }, { "type": "Human", "citation": "Gondo RG, et al. \"Growth hormone-releasing peptide-2 stimulates GH secretion in GH-deficient patients with mutated GH-releasing hormone receptor.\" J Clin Endocrinol Metab, 2001;86(7):3279-83. PMID: 11443201.", "pmid": "11443201" }, { "type": "Review", "citation": " \"Pralmorelin: GHRP 2, GPA 748, growth hormone-releasing peptide 2, KP-102 D, KP-102 LN, KP-102D, KP-102LN.\" Drugs R D, 2004;5(4):236-9. PMID: 15230633.", "pmid": "15230633" }, { "type": "Animal", "citation": "Doi N, et al. \"Pharmacological characteristics of KP-102 (GHRP-2), a potent growth hormone-releasing peptide.\" Arzneimittelforschung, 2004;54(12):857-67. PMID: 15646370.", "pmid": "15646370" }, { "type": "Animal", "citation": "Furuta S, et al. \"General pharmacology of KP-102 (GHRP-2), a potent growth hormone-releasing peptide.\" Arzneimittelforschung, 2004;54(12):868-80. PMID: 15646371.", "pmid": "15646371" }, { "type": "Animal", "citation": "Nasu R, et al. \"Physiologically based pharmacokinetic model for pralmorelin hydrochloride in rats.\" Drug Metab Dispos, 2005;33(10):1488-94. PMID: 16033952.", "pmid": "16033952" }, { "type": "In Vitro", "citation": "Cheng J, et al. \"Growth hormone releasing peptides: a comparison of the growth hormone releasing activities of GHRP-2 and GHRP-6 in rat primary pituitary cells.\" Life Sci, 1997;60(16):1385-92. PMID: 9096259.", "pmid": "9096259" }, { "type": "In Vitro", "citation": "Kageyama K, et al. \"Growth hormone-releasing peptide-2 stimulates secretion and synthesis of adrenocorticotropic hormone in mouse pituitary.\" Regul Pept, 2009;158(1-3):116-20. PMID: 19682503.", "pmid": "19682503" }, { "type": "Review", "citation": "Bowers CY. \"GH releasing peptides--structure and kinetics.\" J Pediatr Endocrinol, 1993;6(1):21-31. PMID: 8374685.", "pmid": "8374685" }, { "type": "other", "citation": "Kaken Pharmaceutical. Injection GHRP Kaken 100 (pralmorelin hydrochloride) package insert, 2nd edition, revised July 2022 (JAPIC; read September 30, 2026): diagnosis of growth hormone deficiency; 100 µg IV in adults, 2 µg/kg up to 100 µg at ages 4 to 17." } ], "interactionCoverage": "partial", "related": [ "ipamorelin", "ghrp-6", "hexarelin", "cjc-1295" ], "lastReviewed": "2026-09-28", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": "Japan (diagnostic use)", "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.2.4", "named": true, "wording": "GHRP-2 (pralmorelin)", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.2.4", "named": true, "wording": "GHRP-2 (pralmorelin)", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "ghrp-6", "name": "GHRP-6", "aliases": [ "Growth Hormone Releasing Peptide 6", "SKF-110679" ], "tier": "full", "category": "growth-hormone", "subcategory": "GHRP / ghrelin receptor agonist", "class": "First-generation growth hormone-releasing peptide — the prototype ghrelin receptor agonist.", "tagline": "The original growth hormone-releasing hexapeptide: a strong, fast releaser in 1990s human tests that also raises ACTH and cortisol.", "oneLiner": "The original growth hormone-releasing hexapeptide (His-D-Trp-Ala-Trp-D-Phe-Lys-NH2), described by Bowers in 1984 and later the template for non-peptide secretagogues such as MK-0677.", "sequence": "His-D-Trp-Ala-Trp-D-Phe-Lys-NH2", "molecularFormula": "C46H56N12O6", "molecularWeight": 873.0, "halfLife": { "value": 2.5, "unit": "hours", "range": "7.6 min distribution, 2.5 h elimination (IV, 9 healthy men)", "notes": "Measured once, after single intravenous doses of 100-400 µg/kg (Eur J Pharm Sci 2013). The growth hormone it releases rises within minutes. The 15-30 minute figure given here before had no source." }, "fdaStatus": "research-only", "approvalDetails": "Never approved anywhere. FDA's 503A list places it in Category 3 (nominated without adequate support) and FDA has listed it in 503B Category 2 (significant safety risks) since September 29, 2023, so it cannot be compounded in the US.", "mechanism": "Agonist at the ghrelin receptor (GHS-R1a). A single 1 µg/kg intravenous dose releases about as much growth hormone as GHRH, and the two together several times more; the response largely depends on an intact hypothalamic-pituitary connection. GHRP-6 also raises ACTH and cortisol, unlike GHRH. In rat pituitary cells it acts through the inositol trisphosphate/diacylglycerol pathway and a rise in intracellular calcium.", "primaryUses": [ "Growth hormone reserve testing in 1990s research", "Ghrelin-receptor and ACTH research", "Tissue-protection research in animals" ], "typicalDose": { "range": "100–300", "unit": "mcg", "frequency": "2–3 times daily", "route": "subcutaneous", "notes": "Community dosing only." }, "evidenceLevel": "medium", "sources": [ { "type": "Human", "citation": "Frieboes RM, et al. \"Growth hormone-releasing peptide-6 stimulates sleep, growth hormone, ACTH and cortisol release in normal man.\" Neuroendocrinology, 1995;61(5):584-9. PMID: 7617137.", "pmid": "7617137" }, { "type": "Human", "citation": "Pombo M, et al. \"Absence of growth hormone (GH) secretion after the administration of either GH-releasing hormone (GHRH), GH-releasing peptide (GHRP-6), or GHRH plus GHRP-6 in children with neonatal pituitary stalk transection.\" J Clin Endocrinol Metab, 1995;80(11):3180-4. PMID: 7593423.", "pmid": "7593423" }, { "type": "Human", "citation": "Bellone J, et al. \"Growth hormone-releasing effect of oral growth hormone-releasing peptide 6 (GHRP-6) administration in children with short stature.\" Eur J Endocrinol, 1995;133(4):425-9. PMID: 7581965.", "pmid": "7581965" }, { "type": "In Vitro", "citation": "Mau SE, et al. \"Growth hormone releasing hexapeptide (GHRP-6) activates the inositol (1,4,5)-trisphosphate/diacylglycerol pathway in rat anterior pituitary cells.\" J Recept Signal Transduct Res, 1995;15(1-4):311-23. PMID: 8903947.", "pmid": "8903947" }, { "type": "Review", "citation": "Pombo M, et al. \"Growth hormone releasing hexapeptide-6 (GHRP-6) test in the diagnosis of GH-deficiency.\" J Pediatr Endocrinol Metab, 1996;9 Suppl 3:333-8. PMID: 8887178.", "pmid": "8887178" }, { "type": "Human", "citation": "Pimentel-Filho FR, et al. \"Growth hormone responses to GH-releasing peptide (GHRP-6) in hypothyroidism.\" Clin Endocrinol (Oxf), 1997;46(3):295-300. PMID: 9156038.", "pmid": "9156038" }, { "type": "Human", "citation": "Nooitgedagt A, et al. \"Influence of endogenous cholinergic tone and growth hormone-releasing peptide-6 on exercise induced growth hormone release.\" Clin Endocrinol (Oxf), 1997;46(2):195-202. PMID: 9135702.", "pmid": "9135702" }, { "type": "Human", "citation": "Borges MH, et al. \"Different effects of growth hormone releasing peptide (GHRP-6) and GH-releasing hormone on GH release in endogenous and exogenous hypercortisolism.\" Clin Endocrinol (Oxf), 1997;46(6):713-8. PMID: 9274702.", "pmid": "9274702" }, { "type": "Human", "citation": "Martins MR, et al. \"GH-releasing peptide (GHRP-6)-induced ACTH release in patients with addison's disease: effect of glucocorticoid withdrawal.\" J Endocrinol Invest, 2003;26(2):143-7. PMID: 12739742.", "pmid": "12739742" }, { "type": "Animal", "citation": "Cibrián D, et al. \"Use of growth-hormone-releasing peptide-6 (GHRP-6) for the prevention of multiple organ failure.\" Clin Sci (Lond), 2006;110(5):563-73. PMID: 16417467.", "pmid": "16417467" }, { "type": "Human", "citation": "Nascif SO, et al. \"Ghrelin and GHRP-6-induced ACTH and cortisol release in thyrotoxicosis.\" Pituitary, 2009;12(4):315-21. PMID: 19396632.", "pmid": "19396632" }, { "type": "Human", "citation": "Cabrales A, et al. \"Pharmacokinetic study of Growth Hormone-Releasing Peptide 6 (GHRP-6) in nine male healthy volunteers.\" Eur J Pharm Sci, 2013;48(1-2):40-6. PMID: 23099431.", "pmid": "23099431" }, { "type": "Animal", "citation": "Rodriguez Salgueiro S, et al. \"Role of epidermal growth factor and growth hormone-releasing peptide-6 in acceleration of renal tissue repair after kanamycin overdosing in rats.\" Iran J Kidney Dis, 2014;8(5):382-8. PMID: 25194405.", "pmid": "25194405" }, { "type": "Animal", "citation": "Berlanga-Acosta J, et al. \"Growth hormone releasing peptide-6 (GHRP-6) prevents doxorubicin-induced myocardial and extra-myocardial damages by activating prosurvival mechanisms.\" Front Pharmacol, 2024;15:1402138. PMID: 38873418.", "pmid": "38873418" }, { "type": "Animal", "citation": "Zhao X, et al. \"Growth hormone-releasing peptide 6 (GHRP-6) hydrogel for acute kidney injury therapy via metabolic regulation.\" J Nanobiotechnology, 2025;24(1):15. PMID: 41327290.", "pmid": "41327290" }, { "type": "pubmed", "citation": "Bowers CY, et al. \"On the in vitro and in vivo activity of a new synthetic hexapeptide that acts on the pituitary to specifically release growth hormone.\" Endocrinology, 1984;114(5):1537-45. PMID: 6714155.", "pmid": "6714155" }, { "type": "pubmed", "citation": "Camanni F, et al. \"Growth hormone-releasing peptides and their analogs.\" Front Neuroendocrinol, 1998;19(1):47-72. PMID: 9465289.", "pmid": "9465289" } ], "interactionCoverage": "partial", "related": [ "ipamorelin", "ghrp-2", "hexarelin", "cjc-1295" ], "lastReviewed": "2026-09-27", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.2.4", "named": true, "wording": "GHRP-6", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.2.4", "named": true, "wording": "GHRP-6", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "gip", "name": "GIP", "aliases": [ "Glucose-dependent Insulinotropic Polypeptide", "Gastric Inhibitory Polypeptide" ], "tier": "mid", "category": "metabolic", "subcategory": "endogenous incretin hormone", "class": "A 42-amino-acid incretin hormone secreted by K-cells in the duodenum and jejunum in response to nutrient ingestion.", "tagline": "The 'other incretin' — the endogenous hormone that tirzepatide and retatrutide co-target alongside GLP-1, driving additive weight loss and metabolic benefits.", "oneLiner": "A 42-amino-acid incretin hormone co-equal to GLP-1 in glucose-dependent insulin secretion, whose receptor is the second target of dual-agonist drugs like tirzepatide.", "sequence": "YAEGTFISDYSIAMDKIHQQDFVNWLLAQKGKKNDWKHNITQ", "molecularFormula": "C225H340N64O68S2", "molecularWeight": 4984.6, "halfLife": { "value": null, "unit": null, "range": "not reported in the sources read", "source": { "type": "none", "note": "searched PubMed on October 1, 2026; no human half-life figure in the sources read" } }, "fdaStatus": "research-only", "approvalDetails": "Not approved as a drug; no application for GIP appears in Drugs@FDA (read October 1, 2026). Its receptor is targeted by approved tirzepatide and investigational retatrutide.", "mechanism": "Binds the GIP receptor (GIPR, a Gs-coupled GPCR) on pancreatic beta cells to stimulate glucose-dependent insulin secretion. Also acts on adipocytes (lipid storage), osteoblasts (bone formation), and centrally (appetite modulation, though the direction of effect is debated). The GIP receptor's role in weight loss vs. weight gain remains actively studied.", "primaryUses": [ "Endogenous incretin physiology", "Target of tirzepatide dual agonism", "Metabolic disease research", "Bone metabolism research" ], "typicalDose": { "range": null, "unit": null, "frequency": null, "route": null, "notes": "Not a medicine. Given by intravenous infusion in research; the 1984 study infused it alongside 10, 20 or 40 g of glucose." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Rosenstock J, et al. \"Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial.\" Lancet, 2021;398(10295):143-155. PMID: 34186022.", "pmid": "34186022" }, { "type": "pubmed", "citation": "Thomas MK, et al. \"Dual GIP and GLP-1 Receptor Agonist Tirzepatide Improves Beta-cell Function and Insulin Sensitivity in Type 2 Diabetes.\" J Clin Endocrinol Metab, 2021;106(2):388-396. PMID: 33236115.", "pmid": "33236115" }, { "type": "pubmed", "citation": "Sarson DL, et al. \"Glucose-dependent insulinotropic polypeptide augmentation of insulin. Physiology or pharmacology?.\" Diabetes, 1984;33(4):389-93. PMID: 6368294.", "pmid": "6368294" }, { "type": "pubmed", "citation": "Jensen MH, et al. \"GIP Receptor Antagonism Eliminates Paradoxical Growth Hormone Secretion in Some Patients With Acromegaly.\" J Clin Endocrinol Metab, 2025;110(3):715-729. PMID: 39172542.", "pmid": "39172542" }, { "type": "pubmed", "citation": "Nauck MA, et al. \"The incretin effect in healthy individuals and those with type 2 diabetes: physiology, pathophysiology, and response to therapeutic interventions.\" Lancet Diabetes Endocrinol, 2016;4(6):525-36. PMID: 26876794.", "pmid": "26876794" }, { "type": "pubmed", "citation": "Campbell JE, et al. \"Pharmacology, physiology, and mechanisms of incretin hormone action.\" Cell Metab, 2013;17(6):819-837. PMID: 23684623.", "pmid": "23684623" } ], "interactionCoverage": "unreviewed", "related": [ "tirzepatide", "retatrutide", "semaglutide", "cagrisema" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-20", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "glatiramer", "name": "Glatiramer Acetate", "aliases": [ "Copaxone", "Glatopa", "Copolymer 1" ], "tier": "mid", "category": "immune", "subcategory": "immunomodulatory peptide polymer", "class": "A random copolymer of four amino acids (glutamic acid, lysine, alanine, tyrosine) that mimics myelin basic protein, FDA-approved for relapsing-remitting multiple sclerosis.", "tagline": "A synthetic peptide polymer for multiple sclerosis — one of the first disease-modifying therapies for MS, mimicking myelin basic protein to shift the immune response from attack to tolerance.", "oneLiner": "A heterogeneous mixture of synthetic polypeptides composed of L-glutamic acid, L-lysine, L-alanine, and L-tyrosine in a defined molar ratio, immunologically mimicking myelin basic protein and approved for relapsing MS since 1996.", "sequence": "Random copolymer of Glu, Lys, Ala, Tyr (molar ratio 1.4:3.4:4.2:1.0)", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": null, "range": "no blood half-life: the label reports that a substantial fraction of each dose is hydrolysed at the injection site", "source": { "type": "label", "ref": "Copaxone (glatiramer acetate) prescribing information, boxed warning and sections 1, 2, 4 and 12.3 (DailyMed SPL version 36, effective June 23, 2026; read October 1, 2026)" } }, "fdaStatus": "approved", "approvalDetails": "Copaxone, NDA 020622, approved December 20, 1996, for relapsing forms of multiple sclerosis including clinically isolated syndrome, relapsing-remitting disease and active secondary progressive disease in adults; generic glatiramer acetate as Glatopa, ANDA 090218, April 16, 2015 (Drugs@FDA, read October 1, 2026).", "mechanism": "Acts as an altered peptide ligand that competes with myelin basic protein for MHC class II binding on antigen-presenting cells. Promotes a Th1→Th2 shift, induces regulatory T cells (Tregs), increases BDNF production by immune cells, and reduces pro-inflammatory cytokine secretion. The immunomodulatory effect is gradual, reducing relapse rates over months.", "primaryUses": [ "Relapsing-remitting multiple sclerosis", "Clinically isolated syndrome" ], "typicalDose": { "range": "20-40", "unit": "mg", "frequency": "20 mg daily or 40 mg three times weekly", "route": "subcutaneous", "notes": "Copaxone label: 20 mg/mL once a day, or 40 mg/mL three times a week at least 48 hours apart. Subcutaneous only, never intravenous, and the two strengths are not interchangeable." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Copaxone (glatiramer acetate) prescribing information, boxed warning and sections 1, 2, 4 and 12.3 (DailyMed SPL version 36, effective June 23, 2026; read October 1, 2026)." }, { "type": "pubmed", "citation": "Johnson KP, et al. \"Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial. The Copolymer 1 Multiple Sclerosis Study Group.\" Neurology, 1995;45(7):1268-76. PMID: 7617181.", "pmid": "7617181" }, { "type": "pubmed", "citation": "Johnson KP, et al. \"Extended use of glatiramer acetate (Copaxone) is well tolerated and maintains its clinical effect on multiple sclerosis relapse rate and degree of disability. Copolymer 1 Multiple Sclerosis Study Group.\" Neurology, 1998;50(3):701-8. PMID: 9521260.", "pmid": "9521260" }, { "type": "pubmed", "citation": "Flechter S, et al. \"Comparison of glatiramer acetate (Copaxone) and interferon beta-1b (Betaferon) in multiple sclerosis patients: an open-label 2-year follow-up.\" J Neurol Sci, 2002;197(1-2):51-5. PMID: 11997066.", "pmid": "11997066" }, { "type": "pubmed", "citation": "Melnikov M, et al. \"The influence of glatiramer acetate on Th17-immune response in multiple sclerosis.\" PLoS One, 2020;15(10):e0240305. PMID: 33126239.", "pmid": "33126239" }, { "type": "pubmed", "citation": "Duda PW, et al. \"Glatiramer acetate (Copaxone) induces degenerate, Th2-polarized immune responses in patients with multiple sclerosis.\" J Clin Invest, 2000;105(7):967-76. PMID: 10749576.", "pmid": "10749576" } ], "interactionCoverage": "none-found", "related": [ "thymosin-alpha-1", "vip" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-20", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "other", "moleculeClassBasis": "random copolymer" }, { "id": "glepaglutide", "name": "Glepaglutide", "aliases": [ "ZP1848" ], "tier": "mid", "category": "pipeline", "subcategory": "long-acting GLP-2 analog (Phase 3)", "class": "A long-acting GLP-2 analog developed by Zealand Pharma with enhanced protease resistance and extended half-life.", "tagline": "A once- or twice-weekly GLP-2 analogue for short bowel syndrome whose phase 3 met its endpoint on the twice-weekly dose.", "oneLiner": "A long-acting analogue of GLP-2, the hormone that makes the remaining intestine absorb more, developed for short bowel syndrome.", "sequence": "GLP-2 analog with protease-resistance modifications", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": "days", "range": "supports twice-weekly dosing", "notes": "Longer than teduglutide (~2 h half-life).", "source": { "type": "qualitative", "note": "a description with no figure; no half-life measurement is cited for it" } }, "fdaStatus": "clinical-trials", "approvalDetails": "Not approved anywhere. The phase 3 trial met its primary endpoint on the 10 mg twice-weekly dose; no application appears in Drugs@FDA.", "mechanism": "GLP-2 receptor agonism with the same intestinotrophic mechanism as teduglutide — enterocyte proliferation, villous expansion, improved nutrient absorption — but administered less frequently owing to extended half-life.", "primaryUses": [ "Short bowel syndrome with intestinal failure (phase 3)" ], "typicalDose": { "range": "10", "unit": "mg", "frequency": "twice weekly", "route": "subcutaneous", "notes": "EASE Phase 3 used 10 mg SC twice weekly." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "Jeppesen PB, et al. \"Glepaglutide, a Long-Acting Glucagon-like Peptide-2 Analogue, Reduces Parenteral Support in Patients With Short Bowel Syndrome: A Phase 3 Randomized Controlled Trial.\" Gastroenterology, 2025;168(4):701-713.e6. PMID: 39708985.", "pmid": "39708985" }, { "type": "pubmed", "citation": "Naimi RM, et al. \"Glepaglutide, a novel long-acting glucagon-like peptide-2 analogue, for patients with short bowel syndrome: a randomised phase 2 trial.\" Lancet Gastroenterol Hepatol, 2019;4(5):354-363. PMID: 30880176.", "pmid": "30880176" }, { "type": "pubmed", "citation": "Naimi RM, et al. \"Effects of glepaglutide, a long-acting glucagon-like peptide-2 analog, on intestinal morphology and perfusion in patients with short bowel syndrome: Findings from a randomized phase 2 trial.\" JPEN J Parenter Enteral Nutr, 2023;47(1):140-150. PMID: 35511704.", "pmid": "35511704" }, { "type": "pubmed", "citation": "Agersnap MA, et al. \"Pharmacokinetics of Glepaglutide, A Long-Acting Glucagon-Like Peptide-2 Analogue: A Study in Healthy Subjects.\" Clin Drug Investig, 2022;42(12):1093-1100. PMID: 36323988.", "pmid": "36323988" }, { "type": "other", "citation": "US FDA, Drugs@FDA (openFDA): no application for glepaglutide. Read September 30, 2026." }, { "type": "clinicaltrials", "citation": "ClinicalTrials.gov NCT03690206: EASE SBS 1, the phase 3 efficacy and safety trial of glepaglutide in short bowel syndrome, completed (registry record read September 30, 2026)." } ], "interactionCoverage": "none-found", "related": [ "teduglutide", "apraglutide" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." } ], "moleculeClass": "peptide", "moleculeClassBasis": "GLP-2 analog" }, { "id": "glp-2", "name": "GLP-2", "aliases": [ "Glucagon-Like Peptide 2" ], "tier": "mid", "category": "metabolic", "subcategory": "endogenous gut hormone", "class": "A 33-amino-acid peptide hormone co-secreted with GLP-1 from intestinal L-cells, with trophic effects specific to the gastrointestinal epithelium.", "tagline": "GLP-1's sibling hormone — a potent intestinal growth factor that drives gut epithelial repair, and the native molecule behind teduglutide (Gattex).", "oneLiner": "A 33-amino-acid gut hormone co-released with GLP-1 from the same proglucagon precursor, uniquely trophic to intestinal epithelium and the basis for teduglutide therapy in short bowel syndrome.", "sequence": "HADGSFSDEMNTILDNLAARDFINWLIQTKITD", "molecularFormula": "C152H222N40O50", "molecularWeight": 3765.2, "halfLife": { "value": null, "unit": null, "range": "not reported in the sources read", "source": { "type": "none", "note": "searched PubMed on October 1, 2026; no human half-life figure in the sources read" } }, "fdaStatus": "research-only", "approvalDetails": "Not approved as a drug; no application for GLP-2 itself appears in Drugs@FDA (read October 1, 2026). Teduglutide (Gattex) was approved under NDA 203441 on December 21, 2012 for short bowel syndrome in patients dependent on parenteral support.", "mechanism": "Binds the GLP-2 receptor on intestinal subepithelial myofibroblasts, triggering release of IGF-1, KGF, and EGF, which collectively stimulate crypt cell proliferation, inhibit apoptosis, and increase villus height, crypt depth, and mucosal blood flow.", "primaryUses": [ "Intestinal adaptation and repair research", "Short bowel syndrome (via teduglutide analog)", "Intestinal failure research", "GI mucosal biology studies" ], "typicalDose": { "range": null, "unit": null, "frequency": null, "route": null, "notes": "Not a medicine. Teduglutide, the approved analogue, requires colonoscopy and upper GI endoscopy with polyp removal before adults start it." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Gattex (teduglutide) prescribing information, sections 1 and 2 (DailyMed SPL version 20, effective September 5, 2025; read October 1, 2026)." }, { "type": "pubmed", "citation": "Jeppesen PB, et al. \"Glepaglutide, a Long-Acting Glucagon-like Peptide-2 Analogue, Reduces Parenteral Support in Patients With Short Bowel Syndrome: A Phase 3 Randomized Controlled Trial.\" Gastroenterology, 2025;168(4):701-713.e6. PMID: 39708985.", "pmid": "39708985" }, { "type": "pubmed", "citation": "Verbiest A, et al. \"Efficacy and safety of apraglutide in short bowel syndrome with intestinal failure and colon-in-continuity: A multicenter, open-label, metabolic balance study.\" Clin Nutr, 2024;43(12):158-166. PMID: 39461299.", "pmid": "39461299" }, { "type": "pubmed", "citation": "Prahm AP, et al. \"Post-prandial secretion of glucagon-like peptide-2 (GLP-2) after carbohydrate-, fat- or protein enriched meals in healthy subjects.\" Peptides, 2023;169:171091. PMID: 37640265.", "pmid": "37640265" }, { "type": "pubmed", "citation": "Syed-Abdul MM, et al. \"Glucagon-like Peptide-2 Acutely Enhances Chylomicron Secretion in Humans Without Mobilizing Cytoplasmic Lipid Droplets.\" J Clin Endocrinol Metab, 2023;108(5):1084-1092. PMID: 36458872.", "pmid": "36458872" }, { "type": "pubmed", "citation": "Ammann M, et al. \"Glucagon-like peptide-1 and glucagon-like peptide-2 regulation during human liver regeneration.\" Sci Rep, 2023;13(1):15980. PMID: 37749369.", "pmid": "37749369" }, { "type": "pubmed", "citation": "Drucker DJ. \"Glucagon-like peptide 2.\" J Clin Endocrinol Metab, 2001;86(4):1759-64. PMID: 11297614.", "pmid": "11297614" } ], "interactionCoverage": "unreviewed", "related": [ "teduglutide", "semaglutide", "liraglutide" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-20", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "glucagon", "name": "Glucagon", "aliases": [ "GlucaGen", "Baqsimi", "Gvoke" ], "tier": "mid", "category": "metabolic", "subcategory": "pancreatic counter-regulatory hormone", "class": "A 29-amino-acid peptide hormone secreted by pancreatic α-cells as the primary counter-regulatory hormone to insulin.", "tagline": "Insulin's counterweight and the rescue drug for severe low blood sugar, now sold as a nasal powder and a ready-filled pen.", "oneLiner": "A 29-amino-acid pancreatic hormone that tells the liver to release glucose, used to treat severe hypoglycaemia.", "sequence": "HSQGTFTSDYSKYLDSRRAQDFVQWLMNT", "molecularFormula": "C153H225N43O49S", "molecularWeight": 3482.75, "halfLife": { "value": 32, "unit": "minutes", "range": "32 minutes for Gvoke after injection", "source": { "type": "label", "ref": "Gvoke prescribing information, section 12.3 (DailyMed version 2, effective July 7, 2026; read September 30, 2026)" } }, "fdaStatus": "approved", "approvalDetails": "FDA-approved in several forms: Baqsimi (glucagon nasal powder, 3 mg, severe hypoglycaemia from age 1), Gvoke (glucagon injection, from age 2, with a separate GVOKE VialDx presentation as a gastrointestinal diagnostic aid), GlucaGen and generic emergency kits.", "mechanism": "Binds the glucagon receptor (a class B GPCR) on hepatocytes, activating adenylyl cyclase, raising cAMP, and driving phosphorylase-mediated glycogenolysis and the gluconeogenic program. The acute rise in blood glucose reverses severe hypoglycemia. Chronic partial glucagon-receptor agonism is the basis for the \"energy-expenditure arm\" of GLP-1/glucagon dual agonists such as pemvidutide, cotadutide, and the glucagon component of retatrutide.", "primaryUses": [ "Severe hypoglycaemia in diabetes (from age 1 nasally, age 2 by pen)", "Diagnostic aid in gastrointestinal procedures" ], "typicalDose": { "range": "1", "unit": "mg (injectable) or 3 mg (nasal)", "frequency": "as needed for hypoglycemic emergency", "route": "subcutaneous, intramuscular, or intranasal", "notes": "Rescue dosing only; not a maintenance medication." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Baqsimi (glucagon) nasal powder Prescribing Information, sections 1 and 2 (DailyMed version 1, effective June 19, 2026; read September 30, 2026)." }, { "type": "fda-pi", "citation": "Gvoke (glucagon) injection Prescribing Information, sections 1 and 2 (DailyMed version 2, effective July 7, 2026; read September 30, 2026)." }, { "type": "pubmed", "citation": "Hövelmann U, et al. \"Pharmacokinetic and Pharmacodynamic Characteristics of Dasiglucagon, a Novel Soluble and Stable Glucagon Analog.\" Diabetes Care, 2018;41(3):531-537. PMID: 29273578.", "pmid": "29273578" }, { "type": "pubmed", "citation": "Pieber TR, et al. \"Immunogenicity of the Novel Glucagon Analogue Dasiglucagon: Results of a Dedicated Immunogenicity Trial in Type 1 Diabetes.\" Diabetes Technol Ther, 2021;23(11):773-776. PMID: 34252289.", "pmid": "34252289" }, { "type": "pubmed", "citation": "Kumar S, et al. \"Glucagon: Delivery advancements for hypoglycemia management.\" Int J Pharm, 2024;652:123785. PMID: 38224759.", "pmid": "38224759" }, { "type": "pubmed", "citation": "Kronfol MM, et al. \"Clinical Pharmacology of Glucagon.\" Clin Pharmacol Ther, 2024;116(4):976-979. PMID: 38847591.", "pmid": "38847591" }, { "type": "pubmed", "citation": "Juel CT, et al. \"Using glucagon receptor antagonism to evaluate the physiological effects of extrapancreatic glucagon in totally pancreatectomised individuals: a randomised controlled trial.\" Diabetologia, 2025;68(12):2807-2822. PMID: 40968190.", "pmid": "40968190" }, { "type": "other", "citation": "US FDA, Drugs@FDA (openFDA): GLUCAGEN, NDA 020918, Discontinued; generic glucagon kits marketed under NDA 201849 and ANDAs 204468, 208086, 214457 and 218813. Read September 30, 2026." } ], "interactionCoverage": "partial", "related": [ "semaglutide", "retatrutide", "pemvidutide" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "glutathione", "name": "Glutathione", "aliases": [ "GSH", "γ-L-glutamyl-L-cysteinylglycine", "gamma-glutamylcysteinylglycine", "reduced glutathione", "L-glutathione" ], "tier": "stub", "category": "longevity", "subcategory": "antioxidant tripeptide", "class": "Endogenous tripeptide of glutamate, cysteine, and glycine joined by an atypical gamma peptide bond. The body's predominant intracellular antioxidant and a central cofactor in Phase II detoxification.", "tagline": "A naturally-occurring tripeptide antioxidant central to cellular redox balance, widely used in injectable longevity and wellness protocols despite limited randomized evidence.", "oneLiner": "Produced endogenously by nearly every cell; marketed as an injectable or IV compound for detoxification, skin lightening, and antioxidant support — with a mechanism that is well-established biochemically but whose therapeutic benefits via exogenous administration remain contested.", "sequence": "γ-Glu-Cys-Gly (with gamma peptide bond between Glu and Cys)", "molecularFormula": "C10H17N3O6S", "molecularWeight": 307.32, "halfLife": { "value": null, "unit": null, "range": "short plasma half-life (minutes to hours)", "notes": "Plasma half-life after IV administration is brief due to rapid enzymatic degradation by gamma-glutamyl transferase. Oral bioavailability is low because of hydrolysis in the GI tract." }, "fdaStatus": "research-only", "approvalDetails": "Not FDA-approved as a standalone injectable drug. Available via compounding pharmacies under 503A. Widely used off-label in IV and subcutaneous wellness protocols, particularly for skin lightening (notably in Southeast Asia), liver support, and general antioxidant therapy. In 2019, the FDA warned against compounded glutathione skin-lightening products due to safety concerns about unregulated sourcing.", "mechanism": "Functions as the primary thiol-based redox buffer in cells. Its cysteine sulfhydryl group donates electrons to neutralize reactive oxygen species (ROS) and free radicals, becoming oxidized to GSSG in the process; GSSG is then recycled back to GSH by glutathione reductase using NADPH. Also serves as a substrate for glutathione S-transferases (GSTs) in Phase II detoxification, conjugating xenobiotics and heavy metals for excretion. Maintains the reduced state of other antioxidants including vitamins C and E, and is controlled transcriptionally by the Nrf2 pathway.", "primaryUses": [ "Injectable antioxidant and 'detox' wellness therapy", "Adjunct treatment in acetaminophen toxicity (via N-acetylcysteine precursor pathway, clinically established)", "Investigational for Parkinson's disease (small pilot trials)", "Off-label skin lightening via injection (unregulated; safety concerns)", "Nebulized forms investigated for pulmonary conditions" ], "typicalDose": { "range": "100–2000", "unit": "mg", "frequency": "1–3x weekly", "route": "IV, subcutaneous, or intramuscular", "notes": "Dosing varies enormously by practitioner and indication. Wellness IV protocols commonly use 600–2000 mg per infusion. Subcutaneous compounded protocols typically 100–300 mg per injection. No FDA-established dose." }, "evidenceLevel": "low", "sources": [ { "type": "review", "citation": "Santacroce G, et al. \"Glutathione: Pharmacological aspects and implications for clinical use in non-alcoholic fatty liver disease.\" Front Med (Lausanne), 2023;10:1124275. PMID: 37035339.", "pmid": "37035339" }, { "type": "review", "citation": "Kalinina E, Novichkova M. \"Glutathione in protein redox modulation through S-glutathionylation and S-nitrosylation.\" Molecules, 2021;26(2):435. PMID: 33467703.", "pmid": "33467703" }, { "type": "pubmed", "citation": "Narayanankutty A, et al. \"Glutathione, an Antioxidant Tripeptide: Dual Roles in Carcinogenesis and Chemoprevention.\" Curr Protein Pept Sci, 2019;20(9):907-917. PMID: 30727890.", "pmid": "30727890" } ], "interactionCoverage": "partial", "related": [ "nad-plus", "thymosin-alpha-1", "ss-31" ], "lastReviewed": "2026-04-20", "publishedAt": "2026-04-20", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Sold as a supplement and compounded for injection, never approved as a drug; how S0 treats it has not been decided. Separately, any infusion or injection of more than 100 mL per 12 hours is a prohibited method (M2.2) unless received in hospital treatment, surgery or clinical investigations." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Sold as a supplement and compounded for injection, never approved as a drug; how S0 treats it has not been decided. Separately, any infusion or injection of more than 100 mL per 12 hours is a prohibited method (M2.2) unless received in hospital treatment, surgery or clinical investigations." } ], "moleculeClass": "peptide" }, { "id": "gma106", "name": "GMA106", "aliases": [ "GMA-106" ], "tier": "stub", "category": "pipeline", "subcategory": "GLP-1 / FGF21 dual agonist (Phase 2)", "class": "A dual GLP-1 receptor agonist / FGF21 analog developed by Gmax Biopharm (China).", "tagline": "Gmax Biopharm's GLP-1 / FGF21 dual-activity candidate — Phase 2 in obesity and MASH; pairs GLP-1 appetite suppression with FGF21's metabolic and hepatic steatosis effects.", "oneLiner": "A dual-activity peptide combining GLP-1 receptor agonism with FGF21 analog activity, developed by Gmax Biopharm (Hangzhou, China), in Phase 2 for obesity and metabolic dysfunction-associated steatohepatitis (MASH); the combination pairs GLP-1 appetite and glycemic effects with FGF21's documented insulin-sensitization and hepatic-steatosis-reduction activity.", "sequence": null, "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": "days", "range": "supports weekly dosing", "notes": "Engineered long-acting fusion protein." }, "fdaStatus": "clinical-trials", "approvalDetails": "Not approved. Phase 2 in China for obesity and MASH.", "mechanism": "Combined GLP-1 receptor agonism and FGF21 receptor (FGFR1c/β-Klotho) agonism in a single molecule. FGF21 signaling drives hepatic fat oxidation, improves insulin sensitivity, and in FGF21-analog clinical trials (pegozafermin, efruxifermin) produces substantial reduction in liver steatosis — complementary to GLP-1 effects.", "primaryUses": [ "Obesity (Phase 2)", "MASH/NASH (Phase 2)" ], "typicalDose": { "range": null, "unit": null, "frequency": "once weekly", "route": "subcutaneous", "notes": "Phase 2 doses not publicly finalized." }, "evidenceLevel": "low", "sources": [ { "type": "manufacturer", "citation": "Gmax Biopharm pipeline page — GMA106 GLP-1/FGF21 dual agonist." } ], "interactionCoverage": "none-found", "related": [ "semaglutide", "pemvidutide" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." } ], "moleculeClass": "peptide" }, { "id": "gonadorelin", "name": "Gonadorelin", "aliases": [ "Factrel", "Lutrepulse", "GnRH", "LHRH", "LH-RH", "luteinizing hormone-releasing hormone" ], "tier": "full", "category": "sexual-health", "subcategory": "GnRH (gonadotropin-releasing hormone)", "class": "Synthetic human gonadotropin-releasing hormone (GnRH), a hypothalamic decapeptide that drives LH and FSH release from the pituitary.", "tagline": "Synthetic GnRH, the hypothalamus's pulse signal for LH and FSH: pumped every 60 to 120 minutes it restored ovulation and sperm production in trials, but as an occasional injection beside testosterone it has never been studied.", "oneLiner": "The endogenous hypothalamic decapeptide gonadotropin-releasing hormone made synthetically, which signals the anterior pituitary to release LH and FSH when delivered in pulses; its US human brands Factrel and Lutrepulse are listed as discontinued, and gonadorelin injections remain FDA-approved for cattle.", "sequence": "pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2", "molecularFormula": "C55H75N17O13", "molecularWeight": 1182.29, "halfLife": { "value": 5, "unit": "minutes", "range": "2.4 min after an IV bolus; 5.5–8 min rapid phase after infusion (12–16.5 min in kidney failure)", "notes": "Three human studies (1977, 1978, 1982). The 4-minute figure given here before had no source; the value above is the midpoint of the measured range, not a measurement." }, "fdaStatus": "discontinued", "approvalDetails": "Two human products were FDA-approved and are listed as discontinued in Drugs@FDA (read September 28, 2026): Factrel (gonadorelin hydrochloride, NDA 018123, approved September 30, 1982) and Lutrepulse (gonadorelin acetate, NDA 019687, approved October 10, 1989, pulsatile infusion). We found no FDA notice giving a reason. Gonadorelin injections remain FDA-approved for cattle (21 CFR 522.1077). Gonadorelin appears in none of the three categories of FDA's 503A nominations list (updated May 14, 2026).", "mechanism": "Binds GnRH receptors on anterior pituitary gonadotroph cells, which release LH and FSH in response. Rhythm decides the effect: in monkeys without their own GnRH, hourly pulses restored gonadotropin secretion while a constant infusion did not and, after pulses, desensitised the pituitary, the effect GnRH agonists exploit for suppression. Pumped every 60 to 120 minutes, gonadorelin restored ovulation in women and sperm production in men with hypogonadotropic hypogonadism.", "primaryUses": [ "Historical (US): pulsatile infusion for hypothalamic amenorrhea (Lutrepulse, discontinued)", "Pulsatile pump therapy for congenital hypogonadotropic hypogonadism in men (studies)", "Stimulation test of pituitary LH reserve (e.g., central precocious puberty)", "Veterinary: ovarian cysts and breeding synchronisation in cattle (FDA-approved)", "Off-label use alongside testosterone therapy as an hCG substitute: no published study" ], "typicalDose": { "range": "1.25–20 per pulse (studies; mostly 2.5–15)", "unit": "mcg", "frequency": "every 60–120 minutes by pump", "route": "intravenous or subcutaneous pump", "notes": "Every human dose with published outcomes was a pulse from a pump: 2.5–5 µg every 60–90 minutes for ovulation induction (Filicori 1994) and 7–15 µg every 90 minutes in men with congenital hypogonadism (2024). No study supplies a dose for occasional injections alongside testosterone therapy. Cattle: 86–100 µg intramuscularly (21 CFR 522.1077)." }, "evidenceLevel": "medium", "sources": [ { "type": "fda-pi", "citation": "US FDA, Drugs@FDA: Factrel (gonadorelin hydrochloride) NDA 018123, original approval September 30, 1982, and Lutrepulse (gonadorelin acetate) NDA 019687, original approval October 10, 1989; both listed as discontinued (read 2026-09-28)." }, { "type": "fda-pi", "citation": "21 CFR 522.1077, Gonadorelin: injectable new animal drug for cattle (eCFR, as of 2026-09-01)." }, { "type": "fda-pi", "citation": "US FDA. Bulk Drug Substances Nominated for Use in Compounding Under Section 503A, Categories 1-3 (updated May 14, 2026): gonadorelin not listed." }, { "type": "Human", "citation": "Santoro N. \"Efficacy and safety of intravenous pulsatile gonadotropin-releasing hormone: Lutrepulse for injection.\" Am J Obstet Gynecol, 1990;163(5 Pt 2):1759-64. PMID: 2122733.", "pmid": "2122733" }, { "type": "Human", "citation": "Filicori M, et al. \"Treatment of anovulation with pulsatile gonadotropin-releasing hormone: prognostic factors and clinical results in 600 cycles.\" J Clin Endocrinol Metab, 1994;79(4):1215-20. PMID: 7962297.", "pmid": "7962297" }, { "type": "Human", "citation": "Blunt SM, et al. \"Pulsatile GnRH therapy for the induction of ovulation in hypogonadotropic hypogonadism.\" Acta Endocrinol Suppl (Copenh), 1988;288:58-65. PMID: 3138867.", "pmid": "3138867" }, { "type": "Human", "citation": "Niu YH, et al. \"[Effect and safety of pulsatile GnRH therapy for male congenital hypogonadotropic hypogonadism].\" Zhonghua Nan Ke Xue, 2024;30(5):404-409. PMID: 39210488.", "pmid": "39210488" }, { "type": "Human", "citation": "Zhang L, et al. \"The Pulsatile Gonadorelin Pump Induces Earlier Spermatogenesis Than Cyclical Gonadotropin Therapy in Congenital Hypogonadotropic Hypogonadism Men.\" Am J Mens Health, 2019;13(1):1557988318818280. PMID: 30569789.", "pmid": "30569789" }, { "type": "Human", "citation": "Fu JF, et al. \"Impact of BMI on gonadorelin-stimulated LH peak in premenarcheal girls with idiopathic central precocious puberty.\" Obesity (Silver Spring), 2015;23(3):637-43. PMID: 25645648.", "pmid": "25645648" }, { "type": "Human", "citation": "Foster WG, et al. \"Immunoglobulin-mediated hypersensitivity in response to long-term treatment with gonadorelin hydrochloride (Factrel) in a female patient.\" Am J Obstet Gynecol, 1989;160(4):979-83. PMID: 2653043.", "pmid": "2653043" }, { "type": "Human", "citation": "Akın O, et al. \"Anaphylaxis to gonadorelin acetate in a girl with central precocious puberty.\" J Pediatr Endocrinol Metab, 2015;28(11-12):1387-9. PMID: 26197466.", "pmid": "26197466" }, { "type": "In Vitro", "citation": "Wong W, et al. \"Stability and purity profile of gonadorelin acetate: a high-purity gonadotropin-releasing hormone.\" Int J Fertil, 1990;35(5):302-9. PMID: 1980667.", "pmid": "1980667" }, { "type": "In Vitro", "citation": "Helm VJ, et al. \"Stability of gonadorelin and triptorelin in aqueous solution.\" Pharm Res, 1990;7(12):1253-6. PMID: 2151342.", "pmid": "2151342" }, { "type": "Animal", "citation": "Souza AH, et al. \"Comparison of gonadorelin products in lactating dairy cows: efficacy based on induction of ovulation of an accessory follicle and circulating luteinizing hormone profiles.\" Theriogenology, 2009;72(2):271-9. PMID: 19394072.", "pmid": "19394072" }, { "type": "Animal", "citation": "Martínez M, et al. \"The effects of 3 gonadorelin products on luteinizing hormone release, ovulation, and follicular wave emergence in cattle.\" Can Vet J, 2003;44(2):125-31. PMID: 12650040.", "pmid": "12650040" }, { "type": "Animal", "citation": "Picard-Hagen N, et al. \"Effect of gonadorelin, lecirelin, and buserelin on LH surge, ovulation, and progesterone in cattle.\" Theriogenology, 2015;84(2):177-83. PMID: 25890780.", "pmid": "25890780" }, { "type": "Animal", "citation": "Melo DB, et al. \"Effect of 200 μg of gonadorelin hydrochloride at the first GnRH of a CO-Synch program on ovulation rate and pregnancies per artificial insemination in Holstein heifers.\" J Dairy Sci, 2024;107(8):6268-6277. PMID: 38460874.", "pmid": "38460874" }, { "type": "Review", "citation": "Torrini F, et al. \"Advances and perspectives in the analytical technology for small peptide hormones analysis: A glimpse to gonadorelin.\" J Pharm Biomed Anal, 2023;228:115312. PMID: 36858006.", "pmid": "36858006" }, { "type": "Human", "citation": "Fauconnier JP, et al. \"Rate of disappearance in plasma of synthetic LH-RH intravenously injected in man.\" Gynecol Obstet Invest, 1978;9(5):229-37. PMID: 378777.", "pmid": "378777" }, { "type": "Human", "citation": "Pimstone B, et al. \"Metabolic clearance and plasma half disappearance time of exogenous gonadotropin releasing hormone in normal subjects and in patients with liver disease and chronic renal failure.\" J Clin Endocrinol Metab, 1977;44(2):356-60. PMID: 320223.", "pmid": "320223" }, { "type": "Human", "citation": "Barron JL, et al. \"Metabolic clearance and plasma half-disappearance time of D-TRP6 and exogenous luteinizing hormone-releasing hormone.\" J Clin Endocrinol Metab, 1982;54(6):1169-73. PMID: 6210706.", "pmid": "6210706" }, { "type": "Animal", "citation": "Belchetz PE, et al. \"Hypophysial responses to continuous and intermittent delivery of hypopthalamic gonadotropin-releasing hormone.\" Science, 1978;202(4368):631-3. PMID: 100883.", "pmid": "100883" } ], "interactionCoverage": "partial", "related": [ "hcg", "sermorelin", "tesamorelin" ], "lastReviewed": "2026-09-28", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.2.1", "named": true, "wording": "GnRH, gonadorelin", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "malesOnly": true, "monitoring": "GnRH analogues in female athletes under 18, in and out of competition" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.2.1", "named": true, "wording": "GnRH, gonadorelin", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "malesOnly": true, "monitoring": "GnRH analogues in female athletes under 18, in and out of competition" } ], "moleculeClass": "peptide" }, { "id": "goserelin", "name": "Goserelin", "aliases": [ "Zoladex" ], "tier": "full", "category": "sexual-health", "subcategory": "GnRH agonist", "class": "Synthetic decapeptide GnRH agonist delivered via subcutaneous biodegradable implant for sustained androgen and estrogen suppression.", "tagline": "Zoladex, a GnRH agonist set in a biodegradable implant placed under the skin every 28 days (3.6 mg) or 12 weeks (10.8 mg, men only). US-approved since 1989 and labelled for prostate cancer and, at 3.6 mg only, for advanced breast cancer before menopause, endometriosis and endometrial thinning.", "oneLiner": "A decapeptide GnRH agonist, D-Ser(tBu)6 with azaglycinamide at position 10, released from a 1-mm lactide-glycolide implant placed in the abdominal wall every 28 days (3.6 mg) or 12 weeks (10.8 mg). Like leuprolide and triptorelin it causes a brief flare and then castrate testosterone or postmenopausal estradiol; the 10.8 mg implant is labelled for men only.", "sequence": "pGlu-His-Trp-Ser-Tyr-D-Ser(tBu)-Leu-Arg-Pro-AzaGly-NH2", "molecularFormula": "C59H84N18O14", "molecularWeight": 1269.4, "halfLife": { "value": 4.2, "unit": "hours", "range": "4.2 h in men, 2.3 h in women after a subcutaneous solution dose; 12.1 h with creatinine clearance under 20 mL/min", "notes": "Blood levels follow the implant's release rate: the 3.6 mg rod releases goserelin over 28 days and the 10.8 mg rod over 12 weeks, with no clinically relevant accumulation (Cockshott 2000; Zoladex labels)." }, "fdaStatus": "approved", "approvalDetails": "FDA-approved as Zoladex: the 3.6 mg implant (NDA 019726, December 29, 1989) and the 10.8 mg implant (NDA 020578, January 11, 1996), both now held by TerSera Therapeutics (Drugs@FDA, read September 28, 2026). 3.6 mg: with flutamide for stage T2b–T4 (B2–C) prostate cancer, starting 8 weeks before radiotherapy; palliative treatment of advanced prostate cancer; endometriosis (6 months, women 18 and older); endometrial thinning before ablation for dysfunctional uterine bleeding; palliative treatment of advanced breast cancer in pre- and perimenopausal women. 10.8 mg: the two prostate indications only; not indicated in women (labels).", "mechanism": "GnRH-receptor agonism on pituitary gonadotrophs — chronic exposure produces receptor desensitization, abolishing pulsatile LH/FSH secretion and producing reversible medical castration.", "primaryUses": [ "Advanced prostate cancer (palliative)", "Stage B2–C prostate cancer (with flutamide + radiotherapy)", "Advanced breast cancer, pre- and perimenopausal women (palliative)", "Endometriosis (6 months)", "Endometrial thinning before endometrial ablation" ], "typicalDose": { "range": "3.6 or 10.8", "unit": "mg", "frequency": "every 28 days (3.6 mg) or every 12 weeks (10.8 mg)", "route": "subcutaneous implant (anterior abdominal wall, below the navel)", "notes": "Placed by a clinician from a preloaded syringe. The 10.8 mg implant is for men only; endometriosis treatment is limited to 6 months (labels)." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Zoladex (goserelin implant) 3.6 mg and 10.8 mg Prescribing Information. TerSera Therapeutics LLC (DailyMed versions published 2026-03-26, read 2026-09-28)." }, { "type": "fda-pi", "citation": "US FDA, Drugs@FDA: Zoladex implant NDA 019726 (3.6 mg, approved 1989-12-29) and NDA 020578 (10.8 mg, approved 1996-01-11), both held by TerSera Therapeutics (read 2026-09-28)." }, { "type": "pubmed", "citation": "Chrisp P, et al. \"Goserelin. A review of its pharmacodynamic and pharmacokinetic properties, and clinical use in sex hormone-related conditions.\" Drugs, 1991;41(2):254-88. PMID: 1709853.", "pmid": "1709853" }, { "type": "pubmed", "citation": "Cockshott ID. \"Clinical pharmacokinetics of goserelin.\" Clin Pharmacokinet, 2000;39(1):27-48. PMID: 10926349.", "pmid": "10926349" }, { "type": "pubmed", "citation": "Tsukagoshi S. \"[A new LH-RH agonist for treatment of prostate cancer, 3-month controlled-release formulation of goserelin acetate (Zoladex LA 10.8 mg depot)--outline of pre-clinical and clinical studies].\" Gan To Kagaku Ryoho, 2002;29(9):1675-87. PMID: 12355959.", "pmid": "12355959" }, { "type": "pubmed", "citation": "Siddall JK, et al. \"Biochemical monitoring of carcinoma of prostate treated with an LH-RH analogue (Zoladex).\" Br J Urol, 1986;58(6):676-82. PMID: 2432985.", "pmid": "2432985" }, { "type": "pubmed", "citation": "Tomera K, et al. \"The gonadotropin-releasing hormone antagonist abarelix depot versus luteinizing hormone releasing hormone agonists leuprolide or goserelin: initial results of endocrinological and biochemical efficacies in patients with prostate cancer.\" J Urol, 2001;165(5):1585-9. PMID: 11342922.", "pmid": "11342922" }, { "type": "pubmed", "citation": "Axcrona K, et al. \"Androgen deprivation therapy for volume reduction, lower urinary tract symptom relief and quality of life improvement in patients with prostate cancer: degarelix vs goserelin plus bicalutamide.\" BJU Int, 2012;110(11):1721-8. PMID: 22500884.", "pmid": "22500884" }, { "type": "pubmed", "citation": "Akaza H. \"Adjuvant goserelin improves clinical disease-free survival and reduces disease-related mortality in patients with locally advanced or localized prostate cancer.\" BJU Int, 2004;93(1):42-6. PMID: 14678365.", "pmid": "14678365" }, { "type": "pubmed", "citation": "Gu C, et al. \"Efficacy and safety of LY01005 versus goserelin implant in Chinese patients with prostate cancer: A multicenter, randomized, open-label, phase III, non-inferiority trial.\" Chin Med J (Engl), 2023;136(10):1207-1215. PMID: 37010251.", "pmid": "37010251" }, { "type": "pubmed", "citation": "Kaufmann M, et al. \"Goserelin, a depot gonadotrophin-releasing hormone agonist in the treatment of premenopausal patients with metastatic breast cancer. German Zoladex Trial Group.\" J Clin Oncol, 1989;7(8):1113-9. PMID: 2526863.", "pmid": "2526863" }, { "type": "pubmed", "citation": "Dixon AR, et al. \"Goserelin (Zoladex) in premenopausal advanced breast cancer: duration of response and survival.\" Br J Cancer, 1990;62(5):868-70. PMID: 2147110.", "pmid": "2147110" }, { "type": "pubmed", "citation": "Boccardo F, et al. \"Ovarian ablation versus goserelin with or without tamoxifen in pre-perimenopausal patients with advanced breast cancer: results of a multicentric Italian study.\" Ann Oncol, 1994;5(4):337-42. PMID: 8075030.", "pmid": "8075030" }, { "type": "pubmed", "citation": "Taylor CW, et al. \"Multicenter randomized clinical trial of goserelin versus surgical ovariectomy in premenopausal patients with receptor-positive metastatic breast cancer: an intergroup study.\" J Clin Oncol, 1998;16(3):994-9. PMID: 9508182.", "pmid": "9508182" }, { "type": "pubmed", "citation": "Jonat W, et al. \"Goserelin versus cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy in premenopausal patients with node-positive breast cancer: The Zoladex Early Breast Cancer Research Association Study.\" J Clin Oncol, 2002;20(24):4628-35. PMID: 12488406.", "pmid": "12488406" }, { "type": "pubmed", "citation": "Baum M, et al. \"Adjuvant goserelin in pre-menopausal patients with early breast cancer: Results from the ZIPP study.\" Eur J Cancer, 2006;42(7):895-904. PMID: 16545560.", "pmid": "16545560" }, { "type": "pubmed", "citation": "Sverrisdottir A, et al. \"Interaction between goserelin and tamoxifen in a prospective randomised clinical trial of adjuvant endocrine therapy in premenopausal breast cancer.\" Breast Cancer Res Treat, 2011;128(3):755-63. PMID: 21625929.", "pmid": "21625929" }, { "type": "pubmed", "citation": "Johansson A, et al. \"Twenty-Year Benefit From Adjuvant Goserelin and Tamoxifen in Premenopausal Patients With Breast Cancer in a Controlled Randomized Clinical Trial.\" J Clin Oncol, 2022;40(35):4071-4082. PMID: 35862873.", "pmid": "35862873" }, { "type": "pubmed", "citation": "McCann KE, et al. \"Goserelin 3-month depot shows non-inferiority to the monthly formulation in U.S. patients with premenopausal breast cancer: a real-world evidence study.\" Breast Cancer Res Treat, 2025;211(2):409-419. PMID: 40050524.", "pmid": "40050524" }, { "type": "pubmed", "citation": "Reichel RP, et al. \"Goserelin (Zoladex) depot in the treatment of endometriosis. Zoladex Endometriosis Study Group.\" Fertil Steril, 1992;57(6):1197-202. PMID: 1534773.", "pmid": "1534773" }, { "type": "pubmed", "citation": "Moghissi KS, et al. \"Goserelin acetate (Zoladex) with or without hormone replacement therapy for the treatment of endometriosis.\" Fertil Steril, 1998;69(6):1056-62. PMID: 9627292.", "pmid": "9627292" }, { "type": "pubmed", "citation": "Soysal ME, et al. \"A randomized controlled trial of goserelin and medroxyprogesterone acetate in the treatment of pelvic congestion.\" Hum Reprod, 2001;16(5):931-9. PMID: 11331640.", "pmid": "11331640" }, { "type": "pubmed", "citation": "Huang X, et al. \"Roles of Goserelin in Gynecological Disorders.\" Drug Des Devel Ther, 2026;20:595029. PMID: 42226753.", "pmid": "42226753" }, { "type": "pubmed", "citation": "Han Q, et al. \"Rapidly dissolving microneedle patch embedded with long-acting microspheres for sustained release of goserelin.\" J Control Release, 2025;388(Pt 2):114397. PMID: 41213385.", "pmid": "41213385" } ], "interactionCoverage": "partial", "related": [ "leuprolide", "triptorelin", "histrelin", "degarelix", "gonadorelin" ], "lastReviewed": "2026-09-28", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.2.1", "named": true, "wording": "goserelin", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "malesOnly": true, "monitoring": "GnRH analogues in female athletes under 18, in and out of competition" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.2.1", "named": true, "wording": "goserelin", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "malesOnly": true, "monitoring": "GnRH analogues in female athletes under 18, in and out of competition" } ], "moleculeClass": "peptide" }, { "id": "gramicidin", "name": "Gramicidin", "aliases": [ "Gramicidin D", "Gramicidin A", "Gramicidin S" ], "tier": "mid", "category": "immune", "subcategory": "Antimicrobial peptide (topical antibiotic)", "class": "Gramicidin was the first antibiotic ever tested clinically (1939) — a channel-forming peptide from soil bacteria still in clinical use in Neosporin-type formulations.", "tagline": "One of the first antibiotics, isolated in 1939: too toxic to swallow or inject, still used in combination eye and ear drops.", "oneLiner": "A channel-forming peptide antibiotic from soil bacteria, used only topically in combination with neomycin and polymyxin B.", "sequence": "HCO-Val-Gly-Ala-D-Leu-Ala-D-Val-Val-D-Val-Trp-D-Leu-Trp-D-Leu-Trp-D-Leu-Trp-NHCH2CH2OH (alternating L/D)", "molecularFormula": "C99H140N20O17", "molecularWeight": 1882.3, "halfLife": { "value": null, "unit": null, "range": "Topical only", "notes": "Too hemolytic for systemic use.", "source": { "type": "qualitative", "note": "a description with no figure; no half-life measurement is cited for it" } }, "fdaStatus": "approved", "approvalDetails": "Used in the US only as a component of topical combination products such as neomycin, polymyxin B and gramicidin ophthalmic solution. Never approved as a systemic drug because it damages human cells.", "mechanism": "Two molecules form a head-to-head beta-helical dimer spanning the bacterial membrane, creating a cation-selective channel (~4 angstrom) that collapses the membrane potential and proton motive force. The alternating L/D amino acid sequence creates a unique beta-helical structure. Effective primarily against Gram-positive bacteria.", "primaryUses": [ "Topical antibiotic in combination eye and ear drops" ], "typicalDose": { "range": "0.025", "unit": "mg/mL (ophthalmic)", "frequency": "2-4 times daily", "route": "topical or ophthalmic only", "notes": "Never given systemically. Combined with bacitracin, polymyxin B, neomycin." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Genée E, et al. \"Trimethoprim-polymyxin eye drops versus neomycin-polymyxin-gramicidin eye drops in the treatment of presumptive bacterial conjunctivitis - a double-blind study.\" Ophthalmologica, 1982;184(2):92-6. PMID: 6174913.", "pmid": "6174913" }, { "type": "pubmed", "citation": "Wadsten CJ, et al. \"A randomized clinical trial of two topical preparations (framycitin/gramicidin and oxytetracycline/hydrocortisone with polymyxin B) in the treatment of external otitis.\" Arch Otorhinolaryngol, 1985;242(2):135-9. PMID: 2415098.", "pmid": "2415098" }, { "type": "pubmed", "citation": "Leach A, et al. \"Topical ciprofloxin versus topical framycetin-gramicidin-dexamethasone in Australian aboriginal children with recently treated chronic suppurative otitis media: a randomized controlled trial.\" Pediatr Infect Dis J, 2008;27(8):692-8. PMID: 18664984.", "pmid": "18664984" }, { "type": "pubmed", "citation": "Notivol R, et al. \"Comparison of topical tobramycin-dexamethasone with dexamethasone-neomycin-polymyxin and neomycin-polymyxin-gramicidin for control of inflammation after cataract surgery: results of a multicenter, prospective, three-arm, randomized, double-masked, controlled, parallel-group study.\" Clin Ther, 2004;26(8):1274-85. PMID: 15476908.", "pmid": "15476908" }, { "type": "pubmed", "citation": "Kelkar DA, et al. \"The gramicidin ion channel: a model membrane protein.\" Biochim Biophys Acta, 2007;1768(9):2011-25. PMID: 17572379.", "pmid": "17572379" }, { "type": "pubmed", "citation": "Dubos RJ. \"STUDIES ON A BACTERICIDAL AGENT EXTRACTED FROM A SOIL BACILLUS : I. PREPARATION OF THE AGENT. ITS ACTIVITY IN VITRO.\" J Exp Med, 1939;70(1):1-10. PMID: 19870884.", "pmid": "19870884" } ], "interactionCoverage": "none-found", "related": [ "bacitracin", "polymyxin-b", "daptomycin", "vancomycin" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-21", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "hbd-1", "name": "hBD-1", "aliases": [ "human β-defensin 1", "DEFB1", "defensin β1", "hBD1" ], "tier": "stub", "category": "immune", "subcategory": "β-defensin (antimicrobial innate immunity peptide)", "class": "A 36-amino-acid cationic antimicrobial β-defensin constitutively expressed by epithelial cells of the urogenital tract, kidney, lung and skin — the founding member of the human β-defensin family.", "tagline": "The constitutive epithelial β-defensin — first isolated from haemodialysate urine by Bensch, Schröder and colleagues (FEBS Letters 1995). Constitutively expressed (unlike hBD-2 and hBD-3, which are inducible), salt-sensitive in standard assays, and a major component of urogenital and airway surface antimicrobial defense.", "oneLiner": "A 36-amino-acid cationic β-defensin with the β-defensin-class three-disulfide fold (Cys1-Cys5, Cys2-Cys4, Cys3-Cys6; distinct connectivity from α-defensins). First isolated from the haemodialysate of patients with chronic renal failure (Bensch, Schnebli, Schulz-Knappe, Schröder et al., FEBS Lett, 1995). Expressed constitutively by epithelial cells lining the urogenital tract, kidney tubules, airways, gingiva and skin; basal expression is not meaningfully inducible by pro-inflammatory cytokines (distinguishing it from hBD-2 and hBD-3). Its activity in vitro is notably salt-sensitive — microbicidal potency falls sharply at physiological NaCl concentrations — which has driven long-running debate about its in-vivo contribution and a hypothesis that disulfide-reduced hBD-1 in the gut has much broader activity than the oxidised form.", "sequence": "DHYNCVSSGGQCLYSACPIFTKIQGTCYRGKAKCCK (disulfides Cys5-Cys34, Cys12-Cys27, Cys17-Cys35)", "molecularFormula": "C170H272N54O46S6", "molecularWeight": 3929.66, "halfLife": { "value": null, "unit": null, "range": "not applicable — endogenous epithelial peptide", "notes": "hBD-1 is secreted at mucosal epithelial surfaces and functions locally. No systemic pharmacokinetic profile." }, "fdaStatus": "research-only", "approvalDetails": "Not a drug. hBD-1 is an endogenous epithelial antimicrobial peptide studied as a research reagent. No β-defensin has been developed as an approved therapeutic, though hBD-1 / hBD-2 / hBD-3 concentrations in saliva, sputum and urine have been studied as biomarkers of infection and inflammation.", "mechanism": "Classical defensin-class mechanism: cationic binding to anionic microbial membranes followed by membrane permeabilisation. Microbicidal spectrum in vitro includes E. coli, Pseudomonas, K. pneumoniae and C. albicans, with weaker Gram-positive activity in the standard oxidised form. A 2011 paper (Schroeder, Wu, Stange, Wehkamp et al., Nature) showed that disulfide-reduced hBD-1 has dramatically broader and more potent activity against anaerobic Gram-positive commensals including bifidobacteria — pointing to a role in shaping mucosal microbiota rather than simply killing invaders. Beyond microbicidal activity, hBD-1 acts as a chemokine for CCR6-expressing immature dendritic cells and memory T cells, linking innate barrier function to adaptive immunity.", "primaryUses": [ "Research reagent for antimicrobial peptide and mucosal immunity studies", "Epithelial biology and barrier research", "Microbiome research on defensin-microbiota interactions", "Clinical biomarker research (salivary, airway, urinary hBD-1 in infection and periodontitis)" ], "typicalDose": { "range": null, "unit": null, "frequency": null, "route": null, "notes": "⚠ No human dosing established. hBD-1 has never been administered as a therapeutic." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Bensch KW, Raida M, Mägert HJ, Schulz-Knappe P, Forssmann WG. \"hBD-1: a novel beta-defensin from human plasma.\" FEBS Lett, 1995;368(2):331-335. (First isolation of hBD-1.) PMID: 7628632.", "pmid": "7628632" }, { "type": "pubmed", "citation": "Schroeder BO, Wu Z, Nuding S, et al. \"Reduction of disulphide bonds unmasks potent antimicrobial activity of human β-defensin 1.\" Nature, 2011;469(7330):419-423. PMID: 21248850.", "pmid": "21248850" }, { "type": "review", "citation": "Ganz T. \"Defensins: antimicrobial peptides of innate immunity.\" Nat Rev Immunol, 2003;3(9):710-720. PMID: 12949495.", "pmid": "12949495" } ], "interactionCoverage": "unreviewed", "related": [ "hbd-2", "hbd-3", "hnp-1", "hd5", "hd6" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "hbd-2", "name": "hBD-2", "aliases": [ "human β-defensin 2", "DEFB4A", "DEFB4", "defensin β2", "hBD2", "SAP1 — skin-antimicrobial peptide 1" ], "tier": "stub", "category": "immune", "subcategory": "β-defensin (antimicrobial innate immunity peptide)", "class": "A 41-amino-acid cationic antimicrobial β-defensin expressed inducibly by epithelial cells in response to bacterial products and pro-inflammatory cytokines; markedly upregulated in psoriatic skin, where it was originally isolated.", "tagline": "The inducible β-defensin — cloned by Harder, Bartels, Christophers and Schröder (Nature 1997) from the lesional scales of psoriasis patients, with the paper framing psoriatic skin as a paradoxical \"almost-never-infected\" phenotype driven by massive β-defensin induction. Induced by TLR / NF-κB signalling in response to bacterial lipopolysaccharide and pro-inflammatory cytokines (IL-1, TNF-α).", "oneLiner": "A 41-amino-acid cationic β-defensin originally purified from the scale extracts of psoriasis patients (Harder, Bartels, Christophers, Schröder; Nature, 1997) and named SAP1 before its defensin assignment was recognised. Unlike hBD-1, hBD-2 expression is strongly inducible by TLR-mediated NF-κB signalling — bacterial LPS, lipoteichoic acid, flagellin and pro-inflammatory cytokines (IL-1β, TNF-α, IL-17) all markedly upregulate DEFB4A transcription in keratinocytes, bronchial epithelium, intestinal epithelium and other barrier epithelia. Expression in psoriatic skin is 100-fold or more above normal, contributing to the low clinical infection rate of psoriatic lesions.", "sequence": "GIGDPVTCLKSGAICHPVFCPRRYKQIGTCGLPGTKCCKKP (disulfides Cys8-Cys37, Cys15-Cys30, Cys20-Cys38)", "molecularFormula": "C192H320N58O51S6", "molecularWeight": 4328.3, "halfLife": { "value": null, "unit": null, "range": "not applicable — endogenous epithelial peptide", "notes": "hBD-2 is secreted at mucosal and skin epithelial surfaces and functions locally. No systemic pharmacokinetic profile." }, "fdaStatus": "research-only", "approvalDetails": "Not a drug, though recombinant hBD-2 has been evaluated as an investigational agent for inflammatory bowel disease and oral mucositis in early-phase work (Defensin Therapeutics / Novozymes recombinant hBD-2; Phase 2 trial in distal ulcerative colitis reported 2023). No regulatory approval as of 2026.", "mechanism": "Classical β-defensin mechanism: cationic membrane permeabilisation of bacterial, fungal and enveloped-viral targets. In-vitro spectrum is broadest against Gram-negative bacteria (E. coli, P. aeruginosa, K. pneumoniae) and C. albicans, with weaker Gram-positive activity. Beyond direct microbicidal activity, hBD-2 is a potent chemokine for CCR6-expressing immature dendritic cells and memory T cells (Yang, Chertov, Bykovskaia, Chen, Buffo, Shogan, Anderson, Schröder, Wang, Howard, Oppenheim; Science 1999) — effectively recruiting adaptive immunity to the site of innate alarm. Also signals through EGFR transactivation in keratinocytes to stimulate wound-edge migration. Induction is NF-κB- and AP-1-dependent; IL-17/IL-22 from Th17 cells are particularly potent inducers in skin and mucosa.", "primaryUses": [ "Research reagent for antimicrobial peptide and epithelial-immunity studies", "Inflammatory skin disease research (psoriasis, atopic dermatitis — where hBD-2 induction is paradoxically reduced)", "Investigational recombinant therapy for ulcerative colitis and mucositis (Phase 2)", "Clinical biomarker research (salivary and sputum hBD-2 in infection and inflammation)" ], "typicalDose": { "range": null, "unit": null, "frequency": null, "route": null, "notes": "⚠ No human dosing established for approved use. Investigational recombinant hBD-2 (Defensin Therapeutics) has been administered orally in early-phase ulcerative colitis trials; specific dose ranges are trial-specific and not yet in general clinical use." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Harder J, Bartels J, Christophers E, Schröder JM. \"A peptide antibiotic from human skin.\" Nature, 1997;387(6636):861. (First isolation of hBD-2.) PMID: 9202117.", "pmid": "9202117" }, { "type": "pubmed", "citation": "Yang D, Chertov O, Bykovskaia SN, et al. \"Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6.\" Science, 1999;286(5439):525-528. PMID: 10521347.", "pmid": "10521347" }, { "type": "review", "citation": "Pazgier M, Hoover DM, Yang D, Lu W, Lubkowski J. \"Human beta-defensins.\" Cell Mol Life Sci, 2006;63(11):1294-1313. PMID: 16710608.", "pmid": "16710608" } ], "interactionCoverage": "unreviewed", "related": [ "hbd-1", "hbd-3", "hnp-1", "hd5", "hd6" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "hbd-3", "name": "hBD-3", "aliases": [ "human β-defensin 3", "DEFB103A", "DEFB103", "defensin β3", "hBD3" ], "tier": "stub", "category": "immune", "subcategory": "β-defensin (antimicrobial innate immunity peptide)", "class": "A 45-amino-acid cationic antimicrobial β-defensin with the broadest microbicidal spectrum and the highest salt tolerance of the human β-defensins — isolated from psoriatic scale and from tonsil tissue in 2001.", "tagline": "The broad-spectrum β-defensin — active against Gram-positive, Gram-negative and fungal targets, and largely salt-insensitive (unlike hBD-1). Isolated independently in 2001 by Harder et al. and by García et al. from psoriatic skin and tonsil respectively. The β-defensin most studied for clinical translation because of its salt tolerance.", "oneLiner": "A 45-amino-acid cationic β-defensin with a net charge of +11 — the most cationic of the major human β-defensins — isolated independently in 2001 by Harder, Bartels, Christophers and Schröder (from psoriatic scale) and by García, Jaumann, Schulz, Krause, Rodríguez-Jiménez, Forssmann, Adermann, Klüver, Vogelmeier, Becker, Hedrich, Forssmann and Bals (from tonsil tissue). Its combination of broad microbicidal spectrum, salt-insensitive activity (retains potency at physiological NaCl), and activity against antibiotic-resistant pathogens (MRSA, VRE) has made hBD-3 the β-defensin most studied for therapeutic translation, though no approved product has emerged.", "sequence": "GIINTLQKYYCRVRGGRCAVLSCLPKEEQIGKCSTRGRKCCRRKK (disulfides Cys11-Cys40, Cys18-Cys33, Cys23-Cys41)", "molecularFormula": "C220H377N77O53S6", "molecularWeight": 5155.15, "halfLife": { "value": null, "unit": null, "range": "not applicable — endogenous epithelial peptide", "notes": "hBD-3 is secreted at mucosal and skin epithelial surfaces and functions locally. No systemic pharmacokinetic profile." }, "fdaStatus": "research-only", "approvalDetails": "Not a drug. hBD-3 has been the subject of multiple preclinical and early-clinical efforts at therapeutic development (topical formulations for MRSA skin infection, catheter-associated infection prophylaxis, burns), none of which have advanced to FDA approval as of 2026. Copy number variation at DEFB103A in the 8p23.1 β-defensin cluster contributes to individual differences in expression levels.", "mechanism": "Classical β-defensin mechanism — cationic membrane permeabilisation — but with several features that distinguish it from hBD-1 and hBD-2. (1) The very high net positive charge (+11) drives efficient membrane binding even at physiological ionic strength, overcoming the salt-sensitivity that limits hBD-1/2 activity in vivo. (2) Broad spectrum in vitro includes Gram-positive bacteria (S. aureus including MRSA, E. faecium including VRE, S. pneumoniae), Gram-negative bacteria (P. aeruginosa, K. pneumoniae, E. coli), fungi (C. albicans), and some enveloped viruses. (3) Dimerisation via hydrophobic interfaces contributes to the pore-forming mechanism and to immunological signalling. Beyond microbicidal activity, hBD-3 is chemotactic via CCR2 (distinct from hBD-2 which uses CCR6), activates monocytes and macrophages through TLR1/TLR2 signalling, and contributes to keratinocyte migration during wound healing. Inducible by similar stimuli to hBD-2 (IL-1β, TNF-α, IL-17, TLR ligands).", "primaryUses": [ "Research reagent for antimicrobial peptide studies", "Preclinical and early-clinical antimicrobial drug development (MRSA, VRE, catheter infection, burn wound)", "Epithelial immunity and wound-healing research", "Clinical biomarker research (airway, saliva, oral mucosa)" ], "typicalDose": { "range": null, "unit": null, "frequency": null, "route": null, "notes": "⚠ No human dosing established. hBD-3 has been evaluated preclinically and in very early clinical work but is not an approved therapeutic." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Harder J, Bartels J, Christophers E, Schröder JM. \"Isolation and characterization of human beta-defensin-3, a novel human inducible peptide antibiotic.\" J Biol Chem, 2001;276(8):5707-5713. PMID: 11085990.", "pmid": "11085990" }, { "type": "pubmed", "citation": "García JR, Krause A, Schulz S, et al. \"Human beta-defensin 4: a novel inducible peptide with a specific salt-sensitive spectrum of antimicrobial activity.\" FASEB J, 2001;15(10):1819-1821. (Early companion β-defensin literature contextualising hBD-3 salt-tolerance.) PMID: 11481241.", "pmid": "11481241" }, { "type": "pubmed", "citation": "Röhrl J, Yang D, Oppenheim JJ, Hehlgans T. \"Human beta-defensin 2 and 3 and their mouse orthologs induce chemotaxis through interaction with CCR2.\" J Immunol, 2010;184(12):6688-6694. PMID: 20483750.", "pmid": "20483750" } ], "interactionCoverage": "unreviewed", "related": [ "hbd-1", "hbd-2", "hnp-1", "hd5", "hd6" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "hcg", "name": "HCG", "aliases": [ "human chorionic gonadotropin", "Pregnyl", "Novarel", "Ovidrel", "choriogonadotropin alfa" ], "tier": "full", "category": "growth-hormone", "subcategory": "gonadotropin", "class": "Glycoprotein hormone structurally related to LH, produced by the placenta during pregnancy and used therapeutically for ovulation induction, male hypogonadism, and cryptorchidism.", "tagline": "A prescription fertility hormone that acts like LH: the IVF trigger and a treatment for male hypogonadism, used off-label beside testosterone on the strength of two small studies, and shown not to work for weight loss.", "oneLiner": "A 237-amino-acid heterodimeric glycoprotein hormone with an alpha subunit shared with LH/FSH/TSH and a unique beta subunit that allows LH-receptor-mediated stimulation of testicular Leydig cells or ovarian corpus luteum.", "sequence": null, "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": 29, "unit": "hours", "range": "29 ± 6 h terminal after subcutaneous injection; 4.5 h initial phase after IV", "notes": "From the Ovidrel (recombinant hCG) label. The ~33–40 hour biphasic figure given here before had no source." }, "fdaStatus": "approved", "approvalDetails": "FDA-approved. Pregnyl and Novarel (purified from the urine of pregnant women) and a generic chorionic gonadotropin: prepubertal cryptorchidism, selected cases of hypogonadotropic hypogonadism in males, and ovulation induction after gonadotropin pretreatment. Ovidrel (recombinant choriogonadotropin alfa): final follicular maturation in assisted reproduction. On March 23, 2020 each approval was deemed a biologics licence (FDA list: Pregnyl NDA 017692, Novarel NDA 017016, Chorionic Gonadotropin NDA 017067, Ovidrel NDA 021149). The Pregnyl and Novarel labels state hCG has not been shown effective for obesity, and FDA says hCG is not approved without a prescription for any purpose.", "mechanism": "Binds the LH receptor: its labels describe its action as virtually identical to pituitary LH, with a small degree of FSH activity. It stimulates testicular Leydig cells to make androgens and the ovarian corpus luteum to make progesterone, and it substitutes for the mid-cycle LH surge that triggers ovulation. In men given testosterone, which suppressed LH to 5% of baseline, 250 to 500 IU every other day kept intratesticular testosterone near or above baseline in a three-week study.", "primaryUses": [ "Final egg maturation (the trigger) in assisted reproduction and ovulation induction", "Male hypogonadotropic hypogonadism", "Prepubertal cryptorchidism", "Off-label: alongside testosterone therapy to keep testicular testosterone up (two small studies); recovery after anabolic steroid use (case reports)" ], "typicalDose": { "range": "500–10,000", "unit": "USP units", "frequency": "varies by indication", "route": "intramuscular (urinary hCG); subcutaneous (Ovidrel 250 µg)", "notes": "Labels: ovulation trigger 5,000–10,000 units once, or Ovidrel 250 µg once; male hypogonadotropic hypogonadism 500–1,000 units three times a week for 3 weeks then twice a week for 3 weeks, or 4,000 units three times a week for 6–9 months then 2,000 units for 3 more months. Studies with testosterone (off-label): 125–500 IU every other day." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Pregnyl (chorionic gonadotropin for injection) Prescribing Information. Organon; revised 03/2025 (DailyMed, read 2026-09-28)." }, { "type": "fda-pi", "citation": "Novarel (chorionic gonadotropin for injection) Prescribing Information. Ferring Pharmaceuticals (DailyMed version of 2025-09-25, read 2026-09-28)." }, { "type": "fda-pi", "citation": "Ovidrel (choriogonadotropin alfa injection) Prescribing Information. EMD Serono (DailyMed version of 2023-12-28, read 2026-09-28)." }, { "type": "Human", "citation": "Coviello AD, et al. \"Low-dose human chorionic gonadotropin maintains intratesticular testosterone in normal men with testosterone-induced gonadotropin suppression.\" J Clin Endocrinol Metab, 2005;90(5):2595-602. PMID: 15713727.", "pmid": "15713727" }, { "type": "Human", "citation": "Hsieh TC, et al. \"Concomitant intramuscular human chorionic gonadotropin preserves spermatogenesis in men undergoing testosterone replacement therapy.\" J Urol, 2013;189(2):647-50. PMID: 23260550.", "pmid": "23260550" }, { "type": "Human", "citation": "Madhusoodanan V, et al. \"Human Chorionic Gonadotropin monotherapy for the treatment of hypogonadal symptoms in men with total testosterone > 300 ng/dL.\" Int Braz J Urol, 2019;45(5):1008-1012. PMID: 31408289.", "pmid": "31408289" }, { "type": "Human", "citation": "Gill GV. \"Anabolic steroid induced hypogonadism treated with human chorionic gonadotropin.\" Postgrad Med J, 1998;74(867):45-6. PMID: 9538490.", "pmid": "9538490" }, { "type": "Human", "citation": "Menon DK. \"Successful treatment of anabolic steroid-induced azoospermia with human chorionic gonadotropin and human menopausal gonadotropin.\" Fertil Steril, 2003;79 Suppl 3:1659-61. PMID: 12801577.", "pmid": "12801577" }, { "type": "Human", "citation": "Kobori Y, et al. \"Hormonal therapy (hCG and rhFSH) for infertile men with adult-onset idiopathic hypogonadotropic hypogonadism.\" Syst Biol Reprod Med, 2015;61(2):110-2. PMID: 25518839.", "pmid": "25518839" }, { "type": "Human", "citation": "Shankar RR, et al. \"Corifollitropin Alfa Combined With Human Chorionic Gonadotropin in Adolescent Boys With Hypogonadotropic Hypogonadism.\" J Clin Endocrinol Metab, 2022;107(7):2036-2046. PMID: 35275602.", "pmid": "35275602" }, { "type": "Human", "citation": "Tamunopriye J, et al. \"Human chorionic gonadotrophin (HCG) stimulation test and testosterone response in children with micropenis.\" Pediatr Endocrinol Rev, 2014;12(1):42-5. PMID: 25345084.", "pmid": "25345084" }, { "type": "Human", "citation": "Morley L, et al. \"Timing of human chorionic gonadotrophin (hCG) hormone administration in IVF protocols using GnRH antagonists: a randomized controlled trial.\" Hum Fertil (Camb), 2012;15(3):134-9. PMID: 22812907.", "pmid": "22812907" }, { "type": "Human", "citation": "Aflatoonian A, et al. \"Efficacy of low-dose hCG in late follicular phase in controlled ovarian stimulation using GnRH agonist protocol.\" Arch Gynecol Obstet, 2012;286(3):771-5. PMID: 22619027.", "pmid": "22619027" }, { "type": "Review", "citation": "Youssef MA, et al. \"Gonadotropin-releasing hormone agonist versus HCG for oocyte triggering in antagonist-assisted reproductive technology.\" Cochrane Database Syst Rev, 2014;2014(10):CD008046. PMID: 25358904.", "pmid": "25358904" }, { "type": "Human", "citation": "van der Merwe R, et al. \"The bioequivalence of liquid and freeze-dried formulations of recombinant human chorionic gonadotrophin.\" Curr Med Res Opin, 2004;20(3):397-402. PMID: 15025848.", "pmid": "15025848" }, { "type": "Review", "citation": "Lijesen GK, et al. \"The effect of human chorionic gonadotropin (HCG) in the treatment of obesity by means of the Simeons therapy: a criteria-based meta-analysis.\" Br J Clin Pharmacol, 1995;40(3):237-43. PMID: 8527285.", "pmid": "8527285" }, { "type": "Human", "citation": "Nome RV, et al. \"Lowered reference limits for hCG improve follow-up of patients with hCG-producing tumors.\" Clin Biochem, 2018;52:73-79. PMID: 29198759.", "pmid": "29198759" }, { "type": "Animal", "citation": "Segal TR, et al. \"Superovulation with human chorionic gonadotropin (hCG) trigger and gonadotropin releasing hormone agonist (GnRHa) trigger differentially alter essential angiogenic factors in the endometrium in a mouse ART model†.\" Biol Reprod, 2020;102(5):1122-1133. PMID: 31995151.", "pmid": "31995151" }, { "type": "Human", "citation": "Borgert BJ, et al. \"The availability of gonadotropin therapy from FDA-approved pharmacies for men with hypogonadism and infertility.\" Sex Med, 2023;11(2):qfad004. PMID: 37051549.", "pmid": "37051549" }, { "type": "fda-pi", "citation": "US FDA. List of Approved NDAs for Biological Products That Were Deemed to be BLAs on March 23, 2020 (chorionic gonadotropin: Pregnyl NDA 017692, Novarel NDA 017016, Chorionic Gonadotropin NDA 017067; choriogonadotropin alfa: Ovidrel NDA 021149)." }, { "type": "fda-pi", "citation": "US FDA. Avoid Dangerous HCG Diet Products (consumer update; content current as of July 13, 2020)." }, { "type": "fda-pi", "citation": "US FDA. Bulk Drug Substances Nominated for Use in Compounding Under Section 503A, Categories 1-3 (updated May 14, 2026): chorionic gonadotropin not listed." } ], "interactionCoverage": "partial", "related": [ "kisspeptin-10", "kisspeptin-54", "somatropin" ], "lastReviewed": "2026-09-28", "publishedAt": "2026-04-18", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.2.1", "named": true, "wording": "chorionic gonadotrophin (CG)", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "malesOnly": true }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.2.1", "named": true, "wording": "chorionic gonadotrophin (CG)", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "malesOnly": true } ], "moleculeClass": "protein", "moleculeClassBasis": "Glycoprotein hormone" }, { "id": "hd5", "name": "HD5", "aliases": [ "human α-defensin 5", "DEFA5", "defensin α5", "enteric α-defensin 5" ], "tier": "mid", "category": "immune", "subcategory": "α-defensin (antimicrobial innate immunity peptide)", "class": "A 32-amino-acid cationic antimicrobial α-defensin produced by small-intestinal Paneth cells — the dominant defensin of the human small bowel — and a key regulator of intestinal microbiota composition.", "tagline": "The Paneth cell α-defensin — the dominant antimicrobial peptide of the human small intestine, stored at millimolar concentrations in Paneth cell secretory granules and released into the crypt lumen upon cholinergic or bacterial stimulus. Reduced HD5 expression is a recognised feature of ileal Crohn disease.", "oneLiner": "A 32-amino-acid cationic α-defensin secreted exclusively by Paneth cells at the base of small-intestinal crypts of Lieberkühn, with a disulfide-stabilised β-sheet fold homologous to HNP-1–3. HD5 is the most abundant antimicrobial peptide of the human small bowel (~50 µg per crypt, ~milligram total output per day), shapes ileal microbiota composition, and is stored as an inactive propeptide that is activated extracellularly by trypsin cleavage. Reduced Paneth cell HD5 expression is a well-documented feature of ileal Crohn disease associated with NOD2 mutations.", "sequence": "ATCYCRTGRCATRESLSGVCEISGRLYRLCCR (disulfides Cys3-Cys31, Cys5-Cys20, Cys10-Cys30)", "molecularFormula": "C155H255N51O39S6", "molecularWeight": 3582.3, "halfLife": { "value": null, "unit": null, "range": "not applicable — endogenous epithelial peptide", "notes": "HD5 is secreted locally into the small-intestinal crypt lumen by Paneth cells and functions in situ. No systemic pharmacokinetic profile.", "source": { "type": "qualitative", "note": "a description with no figure; no half-life measurement is cited for it" } }, "fdaStatus": "research-only", "approvalDetails": "Not a drug. HD5 is an endogenous human Paneth cell defensin studied as a research reagent for mucosal immunity, microbiome, and inflammatory bowel disease research. Synthetic HD5 is commercially available from peptide vendors. Clinical correlates: reduced Paneth-cell HD5 and HD6 expression in ileal Crohn disease has been one of the most reproduced mucosal-immunity findings of the past 20 years, though the therapeutic implications remain unclear.", "mechanism": "Stored as an inactive 94-residue propeptide in Paneth cell secretory granules, then activated extracellularly by trypsin (in mice, by matrilysin/MMP-7) cleavage that releases the mature 32-residue defensin. Mature HD5 acts on microbial membranes by the classical defensin mechanism — cationic binding to anionic bacterial phospholipids and lipid II, followed by membrane permeabilisation. In vitro HD5 is broadly active against Gram-positive bacteria (including L. monocytogenes, E. faecalis, S. aureus), Gram-negative bacteria (E. coli, Salmonella), fungi (C. albicans), and some enveloped viruses. Beyond direct microbicidal activity, HD5 contributes to the shaping of small-intestinal microbiota (mouse Paneth cell defensin ablation, via CR-2-deficient Defa5-expressing transgenics, produces reproducible dysbiosis) and contributes to the ileal barrier against enteric pathogens.", "primaryUses": [ "Research reagent for mucosal antimicrobial peptide studies", "Inflammatory bowel disease research (ileal Crohn disease defensin-deficiency hypothesis)", "Microbiome research on Paneth cell / defensin / microbiota interactions", "Clinical biomarker research (Paneth cell HD5 expression by immunohistochemistry in biopsy samples)" ], "typicalDose": { "range": null, "unit": null, "frequency": null, "route": null, "notes": "⚠ No human dosing established. HD5 has never been administered as a therapeutic." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Pinto-Sánchez MI, et al. \"Bifidobacterium infantis NLS Super Strain Reduces the Expression of α-Defensin-5, a Marker of Innate Immunity, in the Mucosa of Active Celiac Disease Patients.\" J Clin Gastroenterol, 2017;51(9):814-817. PMID: 27636409.", "pmid": "27636409" }, { "type": "pubmed", "citation": "Alkaissi LY, et al. \"Antagonism of Adherent Invasive E. coli LF82 With Human α-defensin 5 in the Follicle-associated Epithelium of Patients With Ileal Crohn's Disease.\" Inflamm Bowel Dis, 2021;27(7):1116-1127. PMID: 33336693.", "pmid": "33336693" }, { "type": "pubmed", "citation": "Porter EM, et al. \"Localization of human intestinal defensin 5 in Paneth cell granules.\" Infect Immun, 1997;65(6):2389-95. PMID: 9169779.", "pmid": "9169779" }, { "type": "pubmed", "citation": "Shukla PK, et al. \"Paneth cell dysfunction in radiation injury and radio-mitigation by human α-defensin 5.\" Front Immunol, 2023;14:1174140. PMID: 37638013.", "pmid": "37638013" } ], "interactionCoverage": "none-found", "related": [ "hd6", "hnp-1", "hbd-1", "hbd-2", "hbd-3" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "hd6", "name": "HD6", "aliases": [ "human α-defensin 6", "DEFA6", "defensin α6", "enteric α-defensin 6" ], "tier": "stub", "category": "immune", "subcategory": "α-defensin (antimicrobial innate immunity peptide)", "class": "A 32-amino-acid cationic antimicrobial α-defensin secreted by Paneth cells; mechanistically distinct from other α-defensins because it acts primarily by forming extracellular fibrillar \"nanonets\" that trap enteric bacteria rather than by direct membrane permeabilisation.", "tagline": "The Paneth cell α-defensin that does not kill directly — HD6 traps enteric pathogens by self-assembling into fibrillar \"nanonets\" (Chu et al., Science 2012), a mechanism unique among the defensin family. Poor microbicidal activity in vitro was a decade-long puzzle until the trapping mechanism was discovered.", "oneLiner": "A 32-amino-acid cationic α-defensin secreted by small-intestinal Paneth cells alongside HD5, sharing the disulfide-stabilised defensin fold but mechanistically distinct. Unlike other α-defensins, HD6 has weak direct microbicidal activity in standard liquid killing assays; its principal function, demonstrated by Chu, Arnold, Lu, Sankaran, Wehkamp, Stange, Bevins and colleagues (Science, 2012), is to self-assemble on contact with bacterial surface proteins into extracellular fibrillar \"nanonets\" that entangle invading enteric pathogens (notably Salmonella typhimurium) and prevent mucosal invasion.", "sequence": "AFTCHCRRSCYSTEYSYGTCTVMGINHRFCCL (disulfides Cys4-Cys31, Cys6-Cys20, Cys11-Cys30)", "molecularFormula": "C152H239N45O42S9", "molecularWeight": 3707.24, "halfLife": { "value": null, "unit": null, "range": "not applicable — endogenous epithelial peptide", "notes": "HD6 is secreted locally into the small-intestinal crypt lumen by Paneth cells and functions in situ. No systemic pharmacokinetic profile." }, "fdaStatus": "research-only", "approvalDetails": "Not a drug. HD6 is an endogenous human Paneth cell defensin studied as a research reagent for mucosal immunity research. Like HD5, Paneth cell HD6 expression is reduced in ileal Crohn disease.", "mechanism": "Unique among α-defensins. Upon Paneth cell degranulation, mature HD6 is released into the crypt lumen where it binds to bacterial surface proteins (including Salmonella flagellin and fimbriae) and self-assembles into higher-order fibrillar nanonets that physically entangle bacteria and prevent mucosal adherence and invasion. Direct membrane-permeabilising microbicidal activity is weak compared to HD5 or HNP-1–3 (explaining early reports that HD6 \"was not a real defensin\"). Mouse knock-in experiments with human DEFA6 showed marked protection against Salmonella invasion that was abolished by mutations disrupting the nanonet-assembly interface — directly validating the trapping mechanism. Also contributes to shaping of ileal microbiota composition alongside HD5.", "primaryUses": [ "Research reagent for mucosal antimicrobial peptide studies", "Inflammatory bowel disease research", "Host-defense research on bacterial trapping and anti-invasion mechanisms", "Template for rational design of anti-invasion mucosal therapeutics (early-stage, no clinical product)" ], "typicalDose": { "range": null, "unit": null, "frequency": null, "route": null, "notes": "⚠ No human dosing established. HD6 has never been administered as a therapeutic." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Chu H, Pazgier M, Jung G, et al. \"Human α-defensin 6 promotes mucosal innate immunity through self-assembled peptide nanonets.\" Science, 2012;337(6093):477-481. PMID: 22722251.", "pmid": "22722251" }, { "type": "pubmed", "citation": "Jones DE, Bevins CL. \"Defensin-6 mRNA in human Paneth cells: implications for antimicrobial peptides in host defense of the human bowel.\" FEBS Lett, 1993;315(2):187-192. PMID: 8417977.", "pmid": "8417977" }, { "type": "pubmed", "citation": "Wehkamp J, Salzman NH, Porter E, et al. \"Reduced Paneth cell alpha-defensins in ileal Crohn disease.\" Proc Natl Acad Sci USA, 2005;102(50):18129-18134. PMID: 16330776.", "pmid": "16330776" } ], "interactionCoverage": "unreviewed", "related": [ "hd5", "hnp-1", "hbd-1", "hbd-2", "hbd-3" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "hexarelin", "name": "Hexarelin", "aliases": [ "Examorelin", "EP 23905", "MF-6003" ], "tier": "full", "category": "growth-hormone", "subcategory": "GHRP / ghrelin receptor agonist", "class": "Synthetic hexapeptide GH secretagogue (ghrelin-receptor agonist) that also binds the cardiac receptor CD36.", "tagline": "A synthetic GH-releasing hexapeptide that outperformed GHRH in small 1990s human studies, also raised cortisol and prolactin, and lost part of its effect with months of use. Never approved.", "oneLiner": "GHRP-6 with a methyl group added to its D-tryptophan (His-D-2-Me-Trp-Ala-Trp-D-Phe-Lys-NH2): a ghrelin-receptor agonist that releases growth hormone and also binds CD36, the basis of its heart research. Examorelin is its nonproprietary name.", "sequence": "His-D-2-Me-Trp-Ala-Trp-D-Phe-Lys-NH2", "molecularFormula": "C47H58N12O6", "molecularWeight": 887.0, "halfLife": { "value": null, "unit": null, "range": "not measured in humans", "notes": "Intravenous half-life 76 minutes in rats (2000) and 120 minutes in dogs (1995). The '55 minutes' once given here is the half-life of the growth hormone it releases (1994)." }, "fdaStatus": "research-only", "approvalDetails": "Never approved. Studied in small human studies in the 1990s and early 2000s, the longest a 16-week course in adults; animal research on the heart continues.", "mechanism": "Agonist at the ghrelin receptor (GHS-R1a) on the pituitary and hypothalamus, releasing growth hormone and, less selectively, ACTH, cortisol and prolactin; synergistic with GHRH. Also binds CD36, a scavenger receptor in heart tissue that a 2014 review credits with its cardioprotective effects in animals. Repeated dosing partly blunts the growth hormone response, which recovers after stopping.", "primaryUses": [ "GH-axis research and diagnostic testing (1990s–2000s)", "Heart research in animal models" ], "typicalDose": { "range": "100–300", "unit": "mcg", "frequency": "1–2 times daily (short cycles only)", "route": "subcutaneous", "notes": "Community figures only; no trial used flat doses. Treatment courses in trials used 1.5 µg/kg (about 105 µg at 70 kg) two or three times daily, and the growth hormone response shrank over 16 weeks." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "Imbimbo BP, et al. \"Growth hormone-releasing activity of hexarelin in humans. A dose-response study.\" Eur J Clin Pharmacol, 1994;46(5):421-5. PMID: 7957536.", "pmid": "7957536" }, { "type": "pubmed", "citation": "Loche S, et al. \"The growth hormone-releasing activity of hexarelin, a new synthetic hexapeptide, in short normal and obese children and in hypopituitary subjects.\" J Clin Endocrinol Metab, 1995;80(2):674-8. PMID: 7852535.", "pmid": "7852535" }, { "type": "pubmed", "citation": "Massoud AF, et al. \"The effect of repeated administration of hexarelin, a growth hormone releasing peptide, and growth hormone releasing hormone on growth hormone responsivity.\" Clin Endocrinol (Oxf), 1996;44(5):555-62. PMID: 8762732.", "pmid": "8762732" }, { "type": "pubmed", "citation": "Rahim A, et al. \"Growth hormone status during long-term hexarelin therapy.\" J Clin Endocrinol Metab, 1998;83(5):1644-9. PMID: 9589671.", "pmid": "9589671" }, { "type": "pubmed", "citation": "Rahim A, et al. \"The effect of chronic hexarelin administration on the pituitary-adrenal axis and prolactin.\" Clin Endocrinol (Oxf), 1999;50(1):77-84. PMID: 10341859.", "pmid": "10341859" }, { "type": "pubmed", "citation": "Maccario M, et al. \"Impact of two or three daily subcutaneous injections of hexarelin, a synthetic growth hormone (GH) secretagogue, on 24-h GH, prolactin, adrenocorticotropin and cortisol secretion in humans.\" Eur J Endocrinol, 2002;146(3):310-8. PMID: 11888836.", "pmid": "11888836" }, { "type": "pubmed", "citation": "Bisi G, et al. \"Cardiac effects of hexarelin in hypopituitary adults.\" Eur J Pharmacol, 1999;381(1):31-8. PMID: 10528131.", "pmid": "10528131" }, { "type": "pubmed", "citation": "Bisi G, et al. \"Acute cardiovascular and hormonal effects of GH and hexarelin, a synthetic GH-releasing peptide, in humans.\" J Endocrinol Invest, 1999;22(4):266-72. PMID: 10342360.", "pmid": "10342360" }, { "type": "pubmed", "citation": "Frieboes RM, et al. \"Hexarelin decreases slow-wave sleep and stimulates the secretion of GH, ACTH, cortisol and prolactin during sleep in healthy volunteers.\" Psychoneuroendocrinology, 2004;29(7):851-60. PMID: 15177700.", "pmid": "15177700" }, { "type": "pubmed", "citation": "Arvat E, et al. \"Endocrine activities of ghrelin, a natural growth hormone secretagogue (GHS), in humans: comparison and interactions with hexarelin, a nonnatural peptidyl GHS, and GH-releasing hormone.\" J Clin Endocrinol Metab, 2001;86(3):1169-74. PMID: 11238504.", "pmid": "11238504" }, { "type": "pubmed", "citation": "Coiro V, et al. \"Desmopressin and hexarelin tests in alcohol-induced pseudo-Cushing's syndrome.\" J Intern Med, 2000;247(6):667-73. PMID: 10886488.", "pmid": "10886488" }, { "type": "review", "citation": "Mao Y, et al. \"The cardiovascular action of hexarelin.\" J Geriatr Cardiol, 2014;11(3):253-8. PMID: 25278975.", "pmid": "25278975" }, { "type": "pubmed", "citation": "Deghenghi R, et al. \"GH-releasing activity of Hexarelin, a new growth hormone releasing peptide, in infant and adult rats.\" Life Sci, 1994;54(18):1321-8. PMID: 7910650.", "pmid": "7910650" }, { "type": "pubmed", "citation": "Roumi M, et al. \"Kinetics and disposition of hexarelin, a peptidic growth hormone secretagogue, in rats.\" Drug Metab Dispos, 2000;28(1):44-50. PMID: 10611139.", "pmid": "10611139" }, { "type": "pubmed", "citation": "Roumi M, et al. \"Radioimmunoassay for hexarelin, a peptidic growth hormone secretagogue, and its pharmacokinetic studies.\" Peptides, 1995;16(7):1301-6. PMID: 8545255.", "pmid": "8545255" }, { "type": "pubmed", "citation": "Rigamonti AE, et al. \"Six-week treatment with hexarelin in young dogs: evaluation of the GH responsiveness to acute hexarelin or GHRH administration, and of the orexigenic effect of hexarelin.\" Eur J Endocrinol, 1999;141(3):313-20. PMID: 10474131.", "pmid": "10474131" }, { "type": "pubmed", "citation": "Mao Y, et al. \"One dose of oral hexarelin protects chronic cardiac function after myocardial infarction.\" Peptides, 2014;56:156-62. PMID: 24747279.", "pmid": "24747279" } ], "interactionCoverage": "partial", "related": [ "ghrp-2", "ghrp-6", "ipamorelin" ], "lastReviewed": "2026-09-26", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.2.4", "named": true, "wording": "examorelin (hexarelin)", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.2.4", "named": true, "wording": "examorelin (hexarelin)", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "hgh-fragment-176-191", "name": "HGH Fragment 176-191", "aliases": [ "HGH Frag 176-191", "Lipolytic fragment of GH", "Frag 176-191" ], "tier": "stub", "category": "research", "subcategory": "growth hormone C-terminal fragment", "class": "A 16-amino-acid synthetic peptide corresponding to residues 176–191 of the human growth hormone C-terminus.", "tagline": "The lipolytic fragment that inspired AOD-9604 — binds a hypothesized non-GHR receptor to drive fat oxidation without growth-promoting effects, though human efficacy data are weak.", "oneLiner": "A synthetic 16-residue peptide reproducing the C-terminal fragment of human growth hormone (residues 176–191), the region proposed by Ng and Bornstein in the 1980s to mediate GH's lipolytic effects independently of its growth-promoting effects, and the direct predecessor to Metabolic Pharmaceuticals' AOD-9604.", "sequence": "YLRIVQCRSVEGSCGF (GH 176-191)", "molecularFormula": "C78H123N23O23S2", "molecularWeight": 1815.1, "halfLife": { "value": null, "unit": "minutes", "range": "<30 minutes plasma", "notes": "Very short; community protocols use daily or twice-daily injection." }, "fdaStatus": "research-only", "approvalDetails": "Not approved for any indication. AOD-9604 (a tyrosine-modified analog of this fragment) was developed by Metabolic Pharmaceuticals for obesity but failed Phase 2b efficacy in 2007. The unmodified Frag 176-191 has no clinical development program and is sold purely as a research chemical.", "mechanism": "Proposed to act through a non-GH-receptor mechanism to stimulate lipolysis and fat oxidation in adipose tissue. Unlike full-length GH, the 176–191 fragment does not stimulate IGF-1 production, does not cause the insulin resistance associated with GH excess, and does not produce growth effects in GH-deficient animal models. The specific receptor mediating these fat-burning effects has never been definitively identified, and the mechanism remains partly hypothetical.", "primaryUses": [ "Fat-loss research (preclinical)", "Community bodybuilding / body-recomposition use (unapproved, weak human efficacy)" ], "typicalDose": { "range": "250–500", "unit": "µg", "frequency": "daily or twice daily", "route": "subcutaneous", "notes": "Community dosing; no clinical validation. AOD-9604 (the analog) failed to show statistically significant weight loss vs placebo at 1 mg/day in a 12-week Phase 2b trial in 534 obese adults." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Ng FM, Bornstein J. \"Hyperglycemic action of synthetic C-terminal fragments of human growth hormone.\" Am J Physiol, 1978;234:E521-526. PMID: 645904.", "pmid": "645904" }, { "type": "pubmed", "citation": "Heffernan M, et al. \"The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice.\" Endocrinology, 2001;142:5182-5189. PMID: 11713213.", "pmid": "11713213" }, { "type": "news-release", "citation": "Metabolic Pharmaceuticals. \"AOD9604 Phase 2b obesity trial results.\" 2007. (Trial failed primary efficacy endpoint.)" } ], "interactionCoverage": "unreviewed", "related": [ "aod-9604", "somatropin", "adipotide" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.2.3", "named": true, "wording": "hGH 176-191", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.2.3", "named": true, "wording": "hGH 176-191", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "histatin", "name": "Histatin", "aliases": [ "Histatin-5", "Histatin-3", "Histatin-1", "Salivary histatins" ], "tier": "mid", "category": "healing", "subcategory": "Endogenous antimicrobial/wound-healing peptide", "class": "Histatins are the histidine-rich antimicrobial peptides in human saliva — they explain why oral wounds heal faster than skin wounds and why saliva has potent antifungal properties.", "tagline": "The histidine-rich salivary peptides that kill Candida and close wounds, trialled twice in dentistry and never marketed.", "oneLiner": "A family of peptides in human saliva whose antifungal and wound-closing activity is why mouth wounds heal faster than skin.", "sequence": "DSHAKRHHGYKRKFHEKHHSHRGY (Histatin-5, 24 aa)", "molecularFormula": "C130H189N47O34", "molecularWeight": 3036.2, "halfLife": { "value": null, "unit": null, "range": "not measured in people in the sources read; broken down by proteases", "source": { "type": "pmid", "pmid": "39631632", "cite": "Lei X, et al. \"The cyclization of human salivary Histatin 1 via click chemistry for skin wound healing.\" Eur J Pharm Sci, 2025;204:106978. PMID: 39631632." } }, "fdaStatus": "research-only", "approvalDetails": "Not approved anywhere. No application for histatin or the P-113 fragment appears in Drugs@FDA; the published human evidence is two experimental gingivitis trials in volunteers from 2001 and 2002.", "mechanism": "Histatin-5 is internalized by Candida via the cell-surface receptor Ssa2, then targets mitochondria, causing loss of membrane potential, ROS generation, and ATP release — a non-lytic killing mechanism. For wound healing, histatins promote epithelial cell migration and fibroblast activity.", "primaryUses": [ "Experimental gingivitis (trial evidence)", "Wound healing research", "Antifungal research" ], "typicalDose": { "range": "N/A", "unit": "N/A", "frequency": "N/A", "route": "endogenous", "notes": "Normal salivary concentration ~30-60 mcg/mL. Xerostomia patients have depleted levels." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "Paquette DW, et al. \"Safety and clinical effects of topical histatin gels in humans with experimental gingivitis.\" J Clin Periodontol, 2002;29(12):1051-8. PMID: 12492903.", "pmid": "12492903" }, { "type": "pubmed", "citation": "Mickels N, et al. \"Clinical and microbial evaluation of a histatin-containing mouthrinse in humans with experimental gingivitis.\" J Clin Periodontol, 2001;28(5):404-10. PMID: 11350502.", "pmid": "11350502" }, { "type": "pubmed", "citation": "Oudhoff MJ, et al. \"Histatins are the major wound-closure stimulating factors in human saliva as identified in a cell culture assay.\" FASEB J, 2008;22(11):3805-12. PMID: 18650243.", "pmid": "18650243" }, { "type": "pubmed", "citation": "Edgerton M, et al. \"Candidacidal activity of salivary histatins. Identification of a histatin 5-binding protein on Candida albicans.\" J Biol Chem, 1998;273(32):20438-47. PMID: 9685398.", "pmid": "9685398" }, { "type": "pubmed", "citation": "Oppenheim FG, et al. \"Histatins, a novel family of histidine-rich proteins in human parotid secretion. Isolation, characterization, primary structure, and fungistatic effects on Candida albicans.\" J Biol Chem, 1988;263(16):7472-7. PMID: 3286634.", "pmid": "3286634" }, { "type": "pubmed", "citation": "Lei X, et al. \"The cyclization of human salivary Histatin 1 via click chemistry for skin wound healing.\" Eur J Pharm Sci, 2025;204:106978. PMID: 39631632.", "pmid": "39631632" }, { "type": "other", "citation": "US FDA, Drugs@FDA (openFDA): no application for histatin or P-113. Read September 30, 2026." } ], "interactionCoverage": "unreviewed", "related": [ "ll-37", "cathelicidin", "bpc-157", "ghk-cu" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-21", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "histrelin", "name": "Histrelin", "aliases": [ "Supprelin LA", "Vantas" ], "tier": "mid", "category": "sexual-health", "subcategory": "GnRH agonist", "class": "Synthetic GnRH agonist delivered via a 12-month subcutaneous hydrogel implant — the longest-acting GnRH agonist formulation available in the United States.", "tagline": "A GnRH agonist implant that suppresses puberty for twelve months at a time; the prostate-cancer version has been discontinued.", "oneLiner": "A nonapeptide GnRH agonist released steadily from a hydrogel implant in the upper arm, replaced once a year.", "sequence": "pGlu-His-Trp-Ser-Tyr-D-His(Bzl)-Leu-Arg-Pro-NHEt", "molecularFormula": "C66H86N18O12", "molecularWeight": 1323.5, "halfLife": { "value": null, "unit": null, "range": "no half-life on the label: the implant keeps serum levels steady through the treatment period", "source": { "type": "label", "ref": "Supprelin LA prescribing information, section 12.3 (DailyMed version 38, effective September 25, 2025; read September 30, 2026)" } }, "fdaStatus": "approved", "approvalDetails": "FDA-approved as Supprelin LA (histrelin acetate) subcutaneous implant, Endo, NDA 022058, for central precocious puberty: one 50 mg implant every 12 months. Vantas (histrelin implant for advanced prostate cancer, NDA 021732) is listed in Drugs@FDA as Discontinued.", "mechanism": "GnRHR agonism with continuous drug release from a subcutaneous polymer implant producing sustained receptor desensitization, abolition of pulsatile LH, and chemical castration. Flare phase is brief.", "primaryUses": [ "Central precocious puberty in children (US label)" ], "typicalDose": { "range": "50", "unit": "mg implant", "frequency": "every 12 months", "route": "subcutaneous implant (inner aspect of upper arm)", "notes": "Implant inserted under local anesthetic via small skin incision; removed and optionally replaced after 12 months. Pediatric use should be reassessed annually based on bone-age progression and clinical pubertal staging." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Supprelin LA (histrelin acetate) subcutaneous implant Prescribing Information, sections 1 and 2. Endo USA (DailyMed version 38, effective September 25, 2025; read September 30, 2026)." }, { "type": "pubmed", "citation": "Eugster EA, et al. \"Efficacy and safety of histrelin subdermal implant in children with central precocious puberty: a multicenter trial.\" J Clin Endocrinol Metab, 2007;92(5):1697-704. PMID: 17327379.", "pmid": "17327379" }, { "type": "pubmed", "citation": "Silverman LA, et al. \"Long-Term Continuous Suppression With Once-Yearly Histrelin Subcutaneous Implants for the Treatment of Central Precocious Puberty: A Final Report of a Phase 3 Multicenter Trial.\" J Clin Endocrinol Metab, 2015;100(6):2354-63. PMID: 25803268.", "pmid": "25803268" }, { "type": "pubmed", "citation": "Schlegel PN. \"Efficacy and safety of histrelin subdermal implant in patients with advanced prostate cancer.\" J Urol, 2006;175(4):1353-8. PMID: 16515997.", "pmid": "16515997" }, { "type": "pubmed", "citation": "Shore N, et al. \"Long-term efficacy and tolerability of once-yearly histrelin acetate subcutaneous implant in patients with advanced prostate cancer.\" BJU Int, 2012;109(2):226-32. PMID: 21851539.", "pmid": "21851539" }, { "type": "pubmed", "citation": "Schlegel PN, et al. \"Effective long-term androgen suppression in men with prostate cancer using a hydrogel implant with the GnRH agonist histrelin.\" Urology, 2001;58(4):578-82. PMID: 11597543.", "pmid": "11597543" }, { "type": "other", "citation": "US FDA, Drugs@FDA (openFDA): SUPPRELIN LA, NDA 022058, Endo, prescription; VANTAS, NDA 021732, Discontinued. Read September 30, 2026." } ], "interactionCoverage": "label", "related": [ "leuprolide", "triptorelin", "goserelin", "nafarelin", "gonadorelin" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.2.1", "named": true, "wording": "histrelin", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "malesOnly": true, "monitoring": "GnRH analogues in female athletes under 18, in and out of competition" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.2.1", "named": true, "wording": "histrelin", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "malesOnly": true, "monitoring": "GnRH analogues in female athletes under 18, in and out of competition" } ], "moleculeClass": "peptide" }, { "id": "hm15136", "name": "HM15136", "aliases": [ "HM-15136", "Efpegerglucagon" ], "tier": "mid", "category": "pipeline", "subcategory": "long-acting glucagon analog", "class": "A long-acting glucagon analog conjugated via Hanmi's LAPSCOVERY platform to an Fc fragment for weekly dosing.", "tagline": "A weekly glucagon analogue in early trials for congenital hyperinsulinism, where raising blood sugar is the point.", "oneLiner": "Glucagon fused to an antibody fragment so one injection lasts about a week, developed for a rare disease of unstoppable insulin release.", "sequence": "Glucagon analog conjugated to IgG4 Fc fragment (LAPSCOVERY platform)", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": 89, "unit": "hours", "range": "77 to 101 hours (terminal)", "source": { "type": "pmid", "pmid": "34726329", "cite": "Huh KY, et al. \"A double-blind, placebo-controlled, single-ascending dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of HM15136, a novel long-acting glucagon analogue, in healthy subjects.\" Diabetes Obes Metab, 2022;24(3):411-420. PMID: 34726329." } }, "fdaStatus": "clinical-trials", "approvalDetails": "Not approved anywhere. Hanmi's long-acting glucagon analogue has orphan designation for congenital hyperinsulinism; the published record is two early-phase trials, a rodent study and one patient treated for ten months under expanded access.", "mechanism": "Chronic weekly glucagon receptor agonism to counteract hyperinsulinemic hypoglycemia. In CHI, pancreatic β-cells oversecrete insulin despite hypoglycemia; sustained glucagon signaling restores hepatic glucose output and prevents neuroglycopenic events. A very different therapeutic use of glucagon from the acute rescue setting (Baqsimi, Gvoke).", "primaryUses": [ "Congenital hyperinsulinism (phase 2, orphan designation)" ], "typicalDose": { "range": null, "unit": null, "frequency": "once weekly", "route": "subcutaneous", "notes": "Phase 2 dosing not publicly finalized." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Huh KY, et al. \"A double-blind, placebo-controlled, single-ascending dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of HM15136, a novel long-acting glucagon analogue, in healthy subjects.\" Diabetes Obes Metab, 2022;24(3):411-420. PMID: 34726329.", "pmid": "34726329" }, { "type": "pubmed", "citation": "Shin W, et al. \"Safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of the novel long-acting glucagon analogue HM15136 in overweight and obese patients with co-morbidities.\" Diabetes Obes Metab, 2023;25(9):2723-2733. PMID: 37311732.", "pmid": "37311732" }, { "type": "pubmed", "citation": "Heo YH, et al. \"A novel glucagon analog with an extended half-life, HM15136, normalizes glucose levels in rodent models of congenital hyperinsulinism.\" Sci Rep, 2022;12(1):16765. PMID: 36202918.", "pmid": "36202918" }, { "type": "pubmed", "citation": "Cannon M, et al. \"Treatment of Congenital Hyperinsulinism With a Novel, Long-acting Glucagon Analogue.\" JCEM Case Rep, 2025;3(11):luaf235. PMID: 41080976.", "pmid": "41080976" }, { "type": "other", "citation": "US FDA, Drugs@FDA (openFDA): no application for HM15136 or efpegerglucagon. Read September 30, 2026." }, { "type": "clinicaltrials", "citation": "ClinicalTrials.gov NCT04732416: phase 2 trial of HM15136 (efpegerglucagon) in congenital hyperinsulinism, ages 2 and over (registry read September 30, 2026)." } ], "interactionCoverage": "none-found", "related": [ "glucagon", "pramlintide" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." } ], "moleculeClass": "peptide-conjugate", "moleculeClassBasis": "conjugated" }, { "id": "hm15275", "name": "HM15275", "aliases": [ "HM-15275" ], "tier": "stub", "category": "pipeline", "subcategory": "GLP-1 / GIP / glucagon triple agonist (Phase 2)", "class": "A triple GLP-1 / GIP / glucagon receptor agonist peptide developed by Hanmi Pharmaceutical.", "tagline": "Hanmi's triple-agonist GLP-1/GIP/glucagon candidate, mechanistically analogous to retatrutide — Phase 2 in obesity with a monthly-dosing ambition enabled by Hanmi's LAPSCOVERY platform.", "oneLiner": "A triple GLP-1 / GIP / glucagon receptor agonist peptide in Phase 2 by Hanmi Pharmaceutical — mechanistically the same class as retatrutide (Lilly) — distinguished by Hanmi's LAPSCOVERY Fc-conjugation platform, which is designed to support less-than-weekly dosing intervals (potentially monthly).", "sequence": null, "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": "days", "range": "LAPSCOVERY-extended", "notes": "Targeting weekly or longer dosing intervals." }, "fdaStatus": "clinical-trials", "approvalDetails": "Not approved. Phase 2 in obesity.", "mechanism": "Balanced triple agonism at GLP-1, GIP, and glucagon receptors — same pharmacological concept as retatrutide. Glucagon agonism adds an energy-expenditure component that drives greater weight loss than dual GLP-1/GIP approaches in preclinical work.", "primaryUses": [ "Obesity (Phase 2)" ], "typicalDose": { "range": null, "unit": null, "frequency": "weekly or less frequent", "route": "subcutaneous", "notes": "Phase 2 doses not publicly finalized." }, "evidenceLevel": "low", "sources": [ { "type": "manufacturer", "citation": "Hanmi Pharmaceutical pipeline page — HM15275 triple agonist." } ], "interactionCoverage": "none-found", "related": [ "retatrutide", "survodutide", "mazdutide" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." } ], "moleculeClass": "peptide" }, { "id": "hnp-1", "name": "HNP-1", "aliases": [ "human neutrophil peptide 1", "human α-defensin 1", "DEFA1", "defensin α1", "myeloid-related sequence peptide 30a" ], "tier": "stub", "category": "immune", "subcategory": "α-defensin (antimicrobial innate immunity peptide)", "class": "A 30-amino-acid cationic antimicrobial α-defensin — the prototype human neutrophil peptide — stored in the azurophilic granules of neutrophils and released into the phagosome and, during degranulation, into the extracellular environment.", "tagline": "The prototype human α-defensin — isolated from neutrophil granules by Ganz, Selsted and Lehrer in 1985; the dominant antimicrobial peptide in human neutrophils and a workhorse molecule of innate immunity. Research peptide only: no defensin has ever been developed as an approved drug.", "oneLiner": "A 30-amino-acid cationic antimicrobial peptide of the α-defensin subfamily, cleaved from the 94-residue prodefensin encoded by DEFA1/DEFA3, stabilised by three intramolecular disulfide bonds (Cys1-Cys6, Cys2-Cys4, Cys3-Cys5) producing the characteristic triple-stranded β-sheet \"defensin fold\". HNP-1 was the first human defensin isolated (Ganz, Selsted, Szklarek, Harwig, Daher, Bainton and Lehrer; J Clin Invest, 1985) and remains the most abundant α-defensin in neutrophil azurophilic granules (milligram quantities per 10⁹ cells in combination with HNP-2 and HNP-3, which together constitute roughly 30–50% of azurophilic granule protein).", "sequence": "ACYCRIPACIAGERRYGTCIYQGRLWAFCC (disulfides Cys2-Cys30, Cys4-Cys19, Cys9-Cys29)", "molecularFormula": "C146H215N41O38S6", "molecularWeight": 3442.06, "halfLife": { "value": null, "unit": null, "range": "not applicable — endogenous granule-stored peptide", "notes": "HNP-1 is released from neutrophil azurophilic granules upon activation and functions locally at the phagosome and inflammatory site. No systemic pharmacokinetic profile has been established because it has never been developed as an exogenous drug." }, "fdaStatus": "research-only", "approvalDetails": "Not a drug. HNP-1 is an endogenous human neutrophil peptide studied as a research reagent for antimicrobial, immunomodulatory, and biomarker purposes. Recombinant and synthetic HNP-1 are available from research vendors (Sigma-Aldrich, Peptides International, Bachem) for in-vitro mechanistic work. Elevated HNP-1/2/3 plasma concentrations have been explored as a biomarker of sepsis, bacterial infection, and inflammatory bowel disease, but no defensin has advanced to regulatory approval as a therapeutic.", "mechanism": "Primary mechanism is direct membrane permeabilisation of microbial targets. The cationic, amphipathic defensin fold binds to anionic bacterial and fungal membrane lipids (lipid II, lipopolysaccharide, lipoteichoic acid, phosphatidylglycerol), then inserts into and destabilises the membrane bilayer — forming transient multimeric pores or disordered patches that dissipate the microbial membrane potential and cause leakage of cytoplasmic contents. HNP-1 has been documented to bind lipid II directly (inhibiting peptidoglycan biosynthesis, like vancomycin does) in addition to its membrane-disrupting activity. Microbicidal spectrum in vitro includes Gram-positive bacteria (S. aureus including MRSA, S. pneumoniae), Gram-negative bacteria (E. coli, P. aeruginosa — though activity is salt-sensitive and can be antagonised by serum), fungi (C. albicans), and enveloped viruses (HSV-1, HIV-1 gp120 binding). Beyond antimicrobial activity, HNP-1 engages multiple host receptors (CCR6-independent chemotaxis of memory T cells and immature dendritic cells, TLR4 activation of antigen-presenting cells, P2Y6 engagement on epithelial cells) and acts as a \"alarmin\" linking innate to adaptive immunity.", "primaryUses": [ "Research reagent for antimicrobial peptide studies", "In-vitro mechanistic research on innate immunity, neutrophil biology, and host-pathogen interaction", "Biomarker research (sepsis, ulcerative colitis, periodontal disease)", "Template for rational design of defensin-mimetic antimicrobial drugs (no approved clinical product yet)" ], "typicalDose": { "range": null, "unit": null, "frequency": null, "route": null, "notes": "⚠ No human dosing established. HNP-1 has never been administered as a therapeutic agent. In-vitro microbicidal assays typically use concentrations of 1–100 µg/mL." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Ganz T, Selsted ME, Szklarek D, Harwig SS, Daher K, Bainton DF, Lehrer RI. \"Defensins. Natural peptide antibiotics of human neutrophils.\" J Clin Invest, 1985;76(4):1427-1435. (First isolation and naming of HNP-1, -2, -3.) PMID: 2997278.", "pmid": "2997278" }, { "type": "review", "citation": "Lehrer RI, Lu W. \"α-Defensins in human innate immunity.\" Immunol Rev, 2012;245(1):84-112. PMID: 22168415.", "pmid": "22168415" }, { "type": "pubmed", "citation": "de Leeuw E, Li C, Zeng P, et al. \"Functional interaction of human neutrophil peptide-1 with the cell wall precursor lipid II.\" FEBS Lett, 2010;584(8):1543-1548. PMID: 20214904.", "pmid": "20214904" } ], "interactionCoverage": "unreviewed", "related": [ "hnp-2", "hnp-3", "hd5", "hd6", "hbd-1", "hbd-2", "hbd-3" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "hnp-2", "name": "HNP-2", "aliases": [ "human neutrophil peptide 2", "human α-defensin 2", "defensin α2" ], "tier": "stub", "category": "immune", "subcategory": "α-defensin (antimicrobial innate immunity peptide)", "class": "A 29-amino-acid cationic antimicrobial α-defensin stored in neutrophil azurophilic granules; differs from HNP-1 only by loss of the N-terminal alanine residue.", "tagline": "The N-terminally truncated HNP-1 variant — 29 residues instead of 30, same disulfide scaffold, the same biological activity profile. A direct proteolytic or post-translational derivative of the prodefensin encoded by DEFA1/DEFA3; isolated alongside HNP-1 and HNP-3 by Ganz et al. in 1985. Research peptide only — no clinical development.", "oneLiner": "A 29-amino-acid cationic α-defensin that differs from HNP-1 by the absence of the N-terminal alanine residue; it is generated from the same DEFA1/DEFA3 prodefensin precursor by variant processing rather than from a distinct gene. HNP-2 was co-isolated with HNP-1 and HNP-3 in the landmark 1985 defensin paper and typically accounts for roughly 20–30% of total HNP content of neutrophil azurophilic granules.", "sequence": "CYCRIPACIAGERRYGTCIYQGRLWAFCC (disulfides Cys1-Cys29, Cys3-Cys18, Cys8-Cys28)", "molecularFormula": "C143H210N40O37S6", "molecularWeight": 3370.98, "halfLife": { "value": null, "unit": null, "range": "not applicable — endogenous granule-stored peptide", "notes": "Like HNP-1 and HNP-3, released from neutrophil azurophilic granules and functions locally. No systemic pharmacokinetic profile; never developed as an exogenous drug." }, "fdaStatus": "research-only", "approvalDetails": "Not a drug. HNP-2 is an endogenous human neutrophil peptide studied primarily as a research reagent. Synthetic and recombinant HNP-2 are available from research vendors. HNP-2 is almost always quantified together with HNP-1 and HNP-3 as \"HNP-1–3\" in clinical biomarker work because they cannot be resolved by standard ELISA and share essentially identical biology.", "mechanism": "Mechanism is functionally equivalent to HNP-1: direct cationic membrane permeabilisation of bacterial, fungal and enveloped viral membranes, plus lipid II binding and a range of immunomodulatory activities including chemotaxis of immature dendritic cells and memory T cells. The single N-terminal alanine deletion does not alter the disulfide-stabilised β-sheet fold and produces no consistent change in microbicidal potency in vitro. Because DEFA1 and DEFA3 genes are highly copy-number variable between individuals, the HNP-1 : HNP-2 : HNP-3 ratio in any given person reflects a combination of gene dosage and post-translational processing efficiency rather than regulated differential expression.", "primaryUses": [ "Research reagent for antimicrobial peptide and neutrophil biology studies", "Biomarker research (HNP-1–3 pooled quantification) in sepsis, bacterial pneumonia, ulcerative colitis, periodontitis, and graft-versus-host disease", "Template for defensin-mimetic antimicrobial drug design" ], "typicalDose": { "range": null, "unit": null, "frequency": null, "route": null, "notes": "⚠ No human dosing established. HNP-2 has never been administered as a therapeutic agent. In-vitro microbicidal concentrations parallel HNP-1 (1–100 µg/mL)." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Ganz T, Selsted ME, Szklarek D, Harwig SS, Daher K, Bainton DF, Lehrer RI. \"Defensins. Natural peptide antibiotics of human neutrophils.\" J Clin Invest, 1985;76(4):1427-1435. PMID: 2997278.", "pmid": "2997278" }, { "type": "review", "citation": "Ganz T. \"Defensins: antimicrobial peptides of innate immunity.\" Nat Rev Immunol, 2003;3(9):710-720. PMID: 12949495.", "pmid": "12949495" }, { "type": "pubmed", "citation": "Linzmeier RM, Ganz T. \"Human defensin gene copy number polymorphisms: comprehensive analysis of independent variation in alpha- and beta-defensin regions at 8p22-p23.\" Genomics, 2005;86(4):423-430. PMID: 16039093.", "pmid": "16039093" } ], "interactionCoverage": "unreviewed", "related": [ "hnp-1", "hnp-3", "hd5", "hd6", "hbd-1", "hbd-2", "hbd-3" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "hnp-3", "name": "HNP-3", "aliases": [ "human neutrophil peptide 3", "human α-defensin 3", "DEFA3", "defensin α3" ], "tier": "stub", "category": "immune", "subcategory": "α-defensin (antimicrobial innate immunity peptide)", "class": "A 30-amino-acid cationic antimicrobial α-defensin stored in neutrophil azurophilic granules; differs from HNP-1 by a single N-terminal residue (Asp instead of Ala).", "tagline": "The third of the three classical neutrophil α-defensins — identical to HNP-1 except the first residue (Asp vs. Ala). Encoded predominantly by DEFA3, a nearly-identical paralog of DEFA1 that arose from segmental duplication. Research peptide only.", "oneLiner": "A 30-amino-acid cationic α-defensin that differs from HNP-1 by a single N-terminal residue substitution — aspartate in place of alanine — and is encoded predominantly by DEFA3, a near-identical paralog of DEFA1 in the DEFA1A3 segmental duplication cluster at chromosome 8p23.1. HNP-3 typically accounts for 10–20% of total HNP content of neutrophil azurophilic granules, with person-to-person variability driven by DEFA1A3 copy number variation.", "sequence": "DCYCRIPACIAGERRYGTCIYQGRLWAFCC (disulfides Cys2-Cys30, Cys4-Cys19, Cys9-Cys29)", "molecularFormula": "C145H213N41O40S6", "molecularWeight": 3486.04, "halfLife": { "value": null, "unit": null, "range": "not applicable — endogenous granule-stored peptide", "notes": "Like HNP-1 and HNP-2, HNP-3 is released locally from neutrophil azurophilic granules. No systemic pharmacokinetic profile." }, "fdaStatus": "research-only", "approvalDetails": "Not a drug. HNP-3 is an endogenous human neutrophil peptide studied as a research reagent. The N-terminal aspartate of HNP-3 introduces a small functional difference — HNP-3 tends to be very slightly less potent than HNP-1 in some in-vitro microbicidal assays, attributed to the acidic N-terminal residue partially neutralising the cationic character that drives membrane binding — but the difference is marginal and clinically irrelevant.", "mechanism": "Same mechanism as HNP-1 and HNP-2: cationic membrane permeabilisation, lipid II binding, immunomodulatory and chemotactic activity. The single Ala → Asp N-terminal substitution produces no change in the disulfide-stabilised fold and only marginal changes in microbicidal potency in vitro (HNP-3 is very slightly less potent than HNP-1 against some Gram-negative targets because the negatively charged aspartate reduces the net cationic charge from +4 to +3).", "primaryUses": [ "Research reagent for antimicrobial peptide studies", "Biomarker research (HNP-1–3 quantification pool) in infection and inflammation", "Population-genetics research on DEFA1A3 copy number variation and infection susceptibility" ], "typicalDose": { "range": null, "unit": null, "frequency": null, "route": null, "notes": "⚠ No human dosing established. HNP-3 has never been administered as a therapeutic agent." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Ganz T, Selsted ME, Szklarek D, Harwig SS, Daher K, Bainton DF, Lehrer RI. \"Defensins. Natural peptide antibiotics of human neutrophils.\" J Clin Invest, 1985;76(4):1427-1435. PMID: 2997278.", "pmid": "2997278" }, { "type": "pubmed", "citation": "Aldred PM, Hollox EJ, Armour JA. \"Copy number polymorphism and expression level variation of the human alpha-defensin genes DEFA1 and DEFA3.\" Hum Mol Genet, 2005;14(14):2045-2052. PMID: 15944200.", "pmid": "15944200" }, { "type": "review", "citation": "Lehrer RI, Lu W. \"α-Defensins in human innate immunity.\" Immunol Rev, 2012;245(1):84-112. PMID: 22168415.", "pmid": "22168415" } ], "interactionCoverage": "unreviewed", "related": [ "hnp-1", "hnp-2", "hd5", "hd6", "hbd-1", "hbd-2", "hbd-3" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "hrs9531", "name": "HRS-9531", "aliases": [ "HRS9531", "KAI-9531" ], "tier": "stub", "category": "pipeline", "subcategory": "GLP-1 / GIP dual agonist (Phase 3, China + global)", "class": "A dual GLP-1 / GIP receptor agonist peptide developed by Jiangsu Hengrui Pharmaceuticals, with ex-China rights licensed to Kailera Therapeutics.", "tagline": "Hengrui's once-weekly GLP-1/GIP dual agonist in Phase 3 in China for obesity, with Kailera Therapeutics holding global ex-China rights since 2024; the structurally closest Chinese competitor to tirzepatide.", "oneLiner": "A once-weekly dual GLP-1 / GIP receptor agonist peptide developed by Jiangsu Hengrui Pharmaceuticals — Phase 3 in China for obesity (2024–2025) with reported ~22% weight loss at 48 weeks at top dose in Phase 2 — and licensed globally (ex-China) to Kailera Therapeutics in May 2024, where it is being developed alongside efpeglenatide as part of a Kailera GLP-1 portfolio.", "sequence": null, "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": "days", "range": "~6–8 days (supports weekly dosing)", "notes": "Lipidated backbone for albumin binding." }, "fdaStatus": "clinical-trials", "approvalDetails": "Not approved. Phase 3 in China in obesity ongoing. Hengrui licensed global ex-China rights to Kailera Therapeutics in May 2024.", "mechanism": "Balanced dual GLP-1 / GIP receptor agonism — mechanistically the same class as tirzepatide. Lipidation provides albumin binding and weekly pharmacokinetics.", "primaryUses": [ "Obesity (Phase 3, China)", "Type 2 diabetes mellitus (Phase 2)" ], "typicalDose": { "range": "1–8", "unit": "mg", "frequency": "once weekly", "route": "subcutaneous", "notes": "Phase 2 explored 1–8 mg weekly dose range." }, "evidenceLevel": "medium", "sources": [ { "type": "manufacturer", "citation": "Jiangsu Hengrui Pharmaceuticals. HRS9531 Phase 2 results press release (2024)." }, { "type": "manufacturer", "citation": "Kailera Therapeutics. Press release: global licensing of HRS-9531 from Hengrui, May 2024." } ], "interactionCoverage": "none-found", "related": [ "tirzepatide", "vk2735", "efpeglenatide" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." } ], "moleculeClass": "peptide" }, { "id": "humanin", "name": "Humanin", "aliases": [ "HN", "MTRNR2", "S14G-Humanin (HNG)" ], "tier": "full", "category": "longevity", "subcategory": "mitochondrial-derived peptide", "class": "A 24-amino-acid mitochondrial-derived peptide encoded in the 16S rRNA gene of mitochondrial DNA.", "tagline": "A 24-amino-acid peptide encoded in mitochondrial DNA: protective in cells and animals, measured but never given in human studies.", "oneLiner": "A 24-amino-acid peptide encoded within the mitochondrial 16S rRNA gene (MTRNR2), with broad cytoprotective effects against Alzheimer-type amyloid toxicity, insulin resistance, and cardiac ischemia.", "sequence": "MAPRGFSCLLLLTSEIDLPVKRRA", "molecularFormula": "C119H204N34O32S2", "molecularWeight": 2687.3, "halfLife": { "value": null, "unit": null, "range": "not measured in the abstracts we hold", "notes": "No pharmacokinetic study of humanin or HNG is in our evidence set. The '~30 minutes' given here before had no source." }, "fdaStatus": "research-only", "approvalDetails": "Not approved anywhere. No published study has given humanin to people; human studies measure its levels in blood or tissue. Not on FDA's 503A bulk-substance category list (updated May 14, 2026).", "mechanism": "Interacts with pro-apoptotic BAX and Bid proteins, preventing their activation and inhibiting apoptosis. Activates STAT3 signaling through a membrane receptor complex. Demonstrates insulin-sensitizing activity via effects on IRS-1 and AMPK. Crosses the blood-brain barrier and shows neuroprotective activity against amyloid-β and prion toxicity in neuronal cultures.", "primaryUses": [ "Alzheimer's disease research (preclinical)", "Metabolic disease research", "Cardiac ischemia-reperfusion research", "Aging biology" ], "typicalDose": { "range": "preclinical", "unit": "", "frequency": "varies", "route": "subcutaneous or IV (preclinical)", "notes": "No human dosing established. Community use carries unknown risk." }, "evidenceLevel": "low", "sources": [ { "type": "Review", "citation": "Niikura T, et al. \"Humanin: after the discovery.\" Mol Neurobiol, 2004;30(3):327-40. PMID: 15655255.", "pmid": "15655255" }, { "type": "Review", "citation": "Nishimoto I, et al. \"Unravelling the role of Humanin.\" Trends Mol Med, 2004;10(3):102-5. PMID: 15106598.", "pmid": "15106598" }, { "type": "Animal", "citation": "Muzumdar RH, et al. \"Humanin: a novel central regulator of peripheral insulin action.\" PLoS One, 2009;4(7):e6334. PMID: 19623253.", "pmid": "19623253" }, { "type": "Review", "citation": "Lee C, et al. \"Humanin: a harbinger of mitochondrial-derived peptides?.\" Trends Endocrinol Metab, 2013;24(5):222-8. PMID: 23402768.", "pmid": "23402768" }, { "type": "In Vitro", "citation": "Hashimoto Y, et al. \"Apollon/Bruce is upregulated by Humanin.\" Mol Cell Biochem, 2014;397(1-2):147-55. PMID: 25138702.", "pmid": "25138702" }, { "type": "Animal", "citation": "Gong Z, et al. \"Central effects of humanin on hepatic triglyceride secretion.\" Am J Physiol Endocrinol Metab, 2015;309(3):E283-92. PMID: 26058861.", "pmid": "26058861" }, { "type": "Human", "citation": "Karu I, et al. \"Exposure to sixty minutes of hyperoxia upregulates myocardial humanins in patients with coronary artery disease - a pilot study.\" J Physiol Pharmacol, 2015;66(6):899-906. PMID: 26769839.", "pmid": "26769839" }, { "type": "Human", "citation": "Gidlund EK, et al. \"Humanin skeletal muscle protein levels increase after resistance training in men with impaired glucose metabolism.\" Physiol Rep, 2016;4(23). PMID: 27923980.", "pmid": "27923980" }, { "type": "In Vitro", "citation": "Nashine S, et al. \"Humanin G (HNG) protects age-related macular degeneration (AMD) transmitochondrial ARPE-19 cybrids from mitochondrial and cellular damage.\" Cell Death Dis, 2017;8(7):e2951. PMID: 28726777.", "pmid": "28726777" }, { "type": "Animal", "citation": "Kim SJ, et al. \"Humanin-induced autophagy plays important roles in skeletal muscle function and lifespan extension.\" Biochim Biophys Acta Gen Subj, 2022;1866(1):130017. PMID: 34624450.", "pmid": "34624450" }, { "type": "Animal", "citation": "Ikegawa N, et al. \"Humanin derivative, HNG, enhances neurotransmitter release.\" Biochim Biophys Acta Gen Subj, 2022;1866(10):130204. PMID: 35843407.", "pmid": "35843407" }, { "type": "Human", "citation": "Nashine S, et al. \"Effect of Humanin G (HNG) on inflammation in age-related macular degeneration (AMD).\" Aging (Albany NY), 2022;14(10):4247-4269. PMID: 35576057.", "pmid": "35576057" }, { "type": "Animal", "citation": "El Kattawy HA, et al. \"Humanin Ameliorates Late-onset Hypogonadism in Aged Male Rats.\" Curr Mol Pharmacol, 2022;15(7):996-1008. PMID: 35086467.", "pmid": "35086467" }, { "type": "Review", "citation": "Gong Z, et al. \"Cardio-protective role of Humanin in myocardial ischemia-reperfusion.\" Biochim Biophys Acta Gen Subj, 2022;1866(2):130066. PMID: 34896254.", "pmid": "34896254" }, { "type": "Human", "citation": "Atreya MR, et al. \"SERUM HUMANIN IN PEDIATRIC SEPTIC SHOCK-ASSOCIATED MULTIPLE-ORGAN DYSFUNCTION SYNDROME.\" Shock, 2024;61(1):83-88. PMID: 37917869.", "pmid": "37917869" }, { "type": "In Vitro", "citation": "Li M, et al. \"[Gly14]-Humanin ameliorates high glucose-induced endothelial senescence via SIRT6.\" Sci Rep, 2024;14(1):30924. PMID: 39730568.", "pmid": "39730568" }, { "type": "In Vitro", "citation": "Maraux M, et al. \"HUMANIN produced by human efferocytic macrophages promotes the resolution of inflammation.\" Cell Death Dis, 2025;16(1):656. PMID: 40877234.", "pmid": "40877234" }, { "type": "In Vitro", "citation": "Morris DL, et al. \"Humanin variants aggregate to produce different fibril morphologies.\" J Biol Chem, 2025;301(7):110403. PMID: 40543583.", "pmid": "40543583" }, { "type": "Human", "citation": "Rodríguez-Esparragón F, et al. \"Insights into the Biomarker Potential of Humanin and Mots-c Expression and Telomere Length in Alzheimer's Disease.\" Int J Mol Sci, 2025;26(22). PMID: 41303353.", "pmid": "41303353" }, { "type": "pubmed", "citation": "Hashimoto Y, et al. \"A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Abeta.\" Proc Natl Acad Sci U S A, 2001;98(11):6336-41. PMID: 11371646.", "pmid": "11371646" } ], "interactionCoverage": "unreviewed", "related": [ "mots-c", "ss-31", "epithalon" ], "lastReviewed": "2026-09-27", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "hyaluronic-acid", "name": "Hyaluronic Acid", "aliases": [ "HA", "Hyaluronan", "Sodium hyaluronate", "Juvéderm", "Restylane", "Synvisc", "Euflexxa" ], "tier": "mid", "category": "cosmetic", "subcategory": "glycosaminoglycan polymer", "class": "Note: Hyaluronic acid is a glycosaminoglycan polymer (repeating disaccharides of D-glucuronic acid and N-acetyl-D-glucosamine), not a peptide. It is included here because injectable HA is a mainstay of the same aesthetic and regenerative-medicine market as peptide therapeutics.", "tagline": "A sugar chain, not a peptide: FDA-approved as fillers and joint injections, brand by brand, with thinner evidence as a supplement.", "oneLiner": "A glycosaminoglycan that binds water in skin, joints and the eye, sold as device-approved fillers and joint injections and as supplements.", "sequence": "Not applicable — HA is a linear polymer of repeating [D-glucuronic acid (β1→3) N-acetyl-D-glucosamine (β1→4)] disaccharides.", "molecularFormula": "(C14H21NO11)n", "molecularWeight": null, "halfLife": { "value": null, "unit": null, "range": "no single figure: it depends on cross-linking and where it is injected", "source": { "type": "none", "note": "varies by product; no single half-life applies" } }, "fdaStatus": "approved", "approvalDetails": "Injectable products are FDA-approved as medical devices through premarket approval, brand by brand: for example Synvisc (P940015, intra-articular) and Juvéderm (P050047, dermal implant). Oral products are sold as supplements; it is not approved as a drug.", "mechanism": "Native HA binds large amounts of water (up to 1000x its mass), providing hydration and structural support in the extracellular matrix. In skin, it interacts with CD44 and RHAMM receptors and influences fibroblast signaling; cross-linked dermal filler additionally stimulates de novo collagen production through sustained mechanical stretching of the surrounding matrix. In joints, injected HA temporarily restores synovial fluid viscoelasticity and may modulate chondrocyte signaling, though systematic reviews disagree on clinical benefit magnitude. In all applications, effects are reversible via endogenous hyaluronidase or deliberate injection of exogenous hyaluronidase.", "primaryUses": [ "Dermal filler (device)", "Knee osteoarthritis injection (device)", "Oral and topical skin products" ], "typicalDose": { "range": "0.5–5", "unit": "mL per session", "frequency": "single procedure; repeat every 6–18 months", "route": "dermal injection, intra-articular injection, or topical", "notes": "Product-specific. Dermal filler: 0.5–2 mL per facial region. Intra-articular knee: 2 mL weekly × 3 injections (single-dose products also available). Concentration commonly 20–25 mg/mL." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Wang F, et al. \"In vivo stimulation of de novo collagen production caused by cross-linked hyaluronic acid dermal filler injections in photodamaged human skin.\" Arch Dermatol, 2007;143(2):155-63. PMID: 17309996.", "pmid": "17309996" }, { "type": "pubmed", "citation": "Gao YR, et al. \"Oral administration of hyaluronic acid to improve skin conditions via a randomized double-blind clinical test.\" Skin Res Technol, 2023;29(11):e13531. PMID: 38009035.", "pmid": "38009035" }, { "type": "pubmed", "citation": "Cai YU, et al. \"Sodium Hyaluronate and Platelet-Rich Plasma for Partial-Thickness Rotator Cuff Tears.\" Med Sci Sports Exerc, 2019;51(2):227-233. PMID: 30199423.", "pmid": "30199423" }, { "type": "pubmed", "citation": "Fallacara A, et al. \"Hyaluronic Acid in the Third Millennium.\" Polymers (Basel), 2018;10(7). PMID: 30960626.", "pmid": "30960626" }, { "type": "pubmed", "citation": "Bellamy N, et al. \"Viscosupplementation for the treatment of osteoarthritis of the knee.\" Cochrane Database Syst Rev, 2006;2006(2):CD005321. PMID: 16625635.", "pmid": "16625635" }, { "type": "pubmed", "citation": "Wongprasert P, et al. \"Evaluating hyaluronic acid dermal fillers: A critique of current characterization methods.\" Dermatol Ther, 2022;35(6):e15453. PMID: 35293660.", "pmid": "35293660" }, { "type": "other", "citation": "US FDA, premarket approval database (openFDA device records): SYNVISC, P940015, Sanofi Genzyme, intra-articular hyaluronic acid; JUVEDERM, P050047, Allergan, dermal implant. Read September 30, 2026." } ], "interactionCoverage": "partial", "related": [ "botulinum-toxin", "ghk-cu", "argireline" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-20", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Not a peptide." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Not a peptide." } ], "moleculeClass": "other", "moleculeClassBasis": "glycosaminoglycan" }, { "id": "icatibant", "name": "Icatibant", "aliases": [ "Firazyr", "HOE 140" ], "tier": "mid", "category": "cardiovascular", "subcategory": "Bradykinin B2 receptor antagonist", "class": "Icatibant is a synthetic decapeptide that blocks bradykinin B2 receptors — FDA-approved for acute hereditary angioedema attacks.", "tagline": "The bradykinin blocker for angioedema — a synthetic decapeptide B2 receptor antagonist that stops acute swelling attacks within 30 minutes.", "oneLiner": "A synthetic 10-amino-acid peptidomimetic that selectively antagonizes bradykinin B2 receptors, FDA-approved for the treatment of acute attacks of hereditary angioedema (HAE) in adults.", "sequence": "H-D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-Tic-Oic-Arg-OH", "molecularFormula": "C59H89N19O13S", "molecularWeight": 1304.52, "halfLife": { "value": null, "unit": null, "range": "not reported in the sources read", "source": { "type": "none", "note": "searched PubMed on October 1, 2026; no human half-life figure in the sources read" } }, "fdaStatus": "approved", "approvalDetails": "Firazyr, NDA 022150, approved August 25, 2011, for acute attacks of hereditary angioedema in adults 18 years and older; generic icatibant is also marketed (Drugs@FDA and the label, read October 1, 2026).", "mechanism": "Selective competitive antagonist at bradykinin B2 receptor. In HAE, C1-esterase inhibitor deficiency leads to excess bradykinin causing vascular leak and edema. Icatibant blocks B2R activation, reversing swelling within 30-60 minutes.", "primaryUses": [ "Acute hereditary angioedema attacks (FDA-approved)", "ACE inhibitor-induced angioedema (off-label)" ], "typicalDose": { "range": "30", "unit": "mg", "frequency": "repeatable at 6-hour intervals, maximum 3 doses in 24 hours", "route": "subcutaneous", "notes": "Firazyr label: 30 mg injected subcutaneously into the abdominal area; if response is inadequate or symptoms recur, further 30 mg injections at intervals of at least six hours, no more than three in 24 hours. Patients may self-administer on recognising an attack." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Firazyr (icatibant) prescribing information, sections 1 and 2 (DailyMed SPL version 19, effective July 7, 2025; read October 1, 2026)." }, { "type": "pubmed", "citation": "Cicardi M, et al. \"Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema.\" N Engl J Med, 2010;363(6):532-41. PMID: 20818888.", "pmid": "20818888" }, { "type": "pubmed", "citation": "Baş M, et al. \"A randomized trial of icatibant in ACE-inhibitor-induced angioedema.\" N Engl J Med, 2015;372(5):418-25. PMID: 25629740.", "pmid": "25629740" }, { "type": "pubmed", "citation": "Sinert R, et al. \"Randomized Trial of Icatibant for Angiotensin-Converting Enzyme Inhibitor-Induced Upper Airway Angioedema.\" J Allergy Clin Immunol Pract, 2017;5(5):1402-1409.e3. PMID: 28552382.", "pmid": "28552382" }, { "type": "pubmed", "citation": "Farkas H, et al. \"Treatment Effect and Safety of Icatibant in Pediatric Patients with Hereditary Angioedema.\" J Allergy Clin Immunol Pract, 2017;5(6):1671-1678.e2. PMID: 28601641.", "pmid": "28601641" }, { "type": "pubmed", "citation": "Leach JK, et al. \"Pharmacokinetics of single and repeat doses of icatibant.\" Clin Pharmacol Drug Dev, 2015;4(2):105-11. PMID: 27128215.", "pmid": "27128215" } ], "interactionCoverage": "label", "related": [ "bradykinin", "angiotensin-ii", "vasopressin" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-21", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "interactionCoverage": "none-found", "lastReviewed": "2026-09-30", "publishedAt": "2026-09-30", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-30" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-30" } ], "moleculeClass": "peptide", "tier": "mid", "fdaStatus": "approved", "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Janssen Biotech. ICOTYDE (icotrokinra) tablets, US prescribing information: indication, dosage (200 mg once daily on waking), warnings (infections, tuberculosis, live vaccines), no contraindications, mechanism (IL-23R, KD 7 pM) and pharmacokinetics (half-life about 12 hours). DailyMed version effective March 17, 2026; read September 30, 2026." }, { "type": "pubmed", "citation": "Gold LS, et al. \"Once-daily oral icotrokinra versus placebo and once-daily oral deucravacitinib in participants with moderate-to-severe plaque psoriasis (ICONIC-ADVANCE 1 & 2): two phase 3, randomised, placebo-controlled and active-comparator-controlled trials.\" Lancet, 2025;406(10510):1363-1374. PMID: 40976249.", "pmid": "40976249" }, { "type": "pubmed", "citation": "Stein Gold L, et al. \"Durability of response to icotrokinra in adults with moderate-to-severe plaque psoriasis: 1-year results from the phase III, placebo- and active comparator-controlled ICONIC-ADVANCE 1 and ICONIC-ADVANCE 2 trials.\" Br J Dermatol, 2026;195(4):600. PMID: 42397072.", "pmid": "42397072" }, { "type": "pubmed", "citation": "Lebwohl MG, et al. \"Safety of Icotrokinra Through 1 Year for the Treatment of Moderate-to-Severe Plaque Psoriasis and Psoriasis Affecting High-Impact Sites: Pooled Results Across the ICONIC-LEAD, ICONIC-TOTAL, and ICONIC-ADVANCE 1 and 2 Phase 3 Trials.\" Dermatol Ther (Heidelb), 2026. PMID: 42663861.", "pmid": "42663861" }, { "type": "pubmed", "citation": "Fourie AM, et al. \"JNJ-77242113, a highly potent, selective peptide targeting the IL-23 receptor, provides robust IL-23 pathway inhibition upon oral dosing in rats and humans.\" Sci Rep, 2024;14(1):17515. PMID: 39080319.", "pmid": "39080319" }, { "type": "pubmed", "citation": "Bissonnette R, et al. \"An Oral Interleukin-23-Receptor Antagonist Peptide for Plaque Psoriasis.\" N Engl J Med, 2024;390(6):510-521. PMID: 38324484.", "pmid": "38324484" }, { "type": "fda", "citation": "FDA. Drugs@FDA (openFDA): ICOTYDE NDA 220149, approved March 17, 2026; and FDA, Novel Drug Approvals for 2026 (content current as of September 28, 2026). Read September 30, 2026." }, { "type": "other", "citation": "European Medicines Agency. Medicines register: Icotyde, authorised September 18, 2026. Read September 30, 2026." } ], "id": "icotrokinra", "name": "Icotrokinra", "aliases": [ "Icotyde", "JNJ-77242113", "JNJ-2113" ], "category": "immune", "subcategory": "oral IL-23 receptor antagonist peptide", "class": "A 13-amino-acid oral peptide that blocks the interleukin-23 receptor; FDA-approved as Icotyde in March 2026 for moderate-to-severe plaque psoriasis.", "tagline": "Johnson & Johnson's oral IL-23 receptor-blocking peptide, approved by FDA as Icotyde on March 17, 2026 for moderate-to-severe plaque psoriasis from age 12: in two phase 3 trials 68-70% had clear or almost clear skin at week 16.", "oneLiner": "A 13-amino-acid peptide taken as a daily tablet that binds the IL-23 receptor (dissociation constant 7 pM) and blocks IL-23 signalling; FDA-approved March 17, 2026 as Icotyde (Janssen Biotech, NDA 220149) for moderate-to-severe plaque psoriasis in adults and in children 12 and older weighing at least 40 kg; authorised in the EU on September 18, 2026.", "sequence": "13-amino-acid peptide with a disulfide-bridged ring and non-natural residues; structure in the Icotyde label, section 11 (hydrochloride salt)", "molecularFormula": "C90H120N20O22S2", "molecularWeight": 1898.2, "halfLife": { "value": 12, "unit": "hours", "range": "about 12 hours", "source": { "type": "label", "ref": "Icotyde prescribing information, section 12.3 (DailyMed version 2, effective March 17, 2026; read September 30, 2026)" } }, "approvalDetails": "FDA: ICOTYDE (icotrokinra) tablets, NDA 220149 (Janssen Biotech), approved March 17, 2026 for moderate-to-severe plaque psoriasis in adults and pediatric patients 12 years and older weighing at least 40 kg who are candidates for systemic therapy or phototherapy (Drugs@FDA; FDA Novel Drug Approvals for 2026). EU: Icotyde authorised September 18, 2026 (EMA register).", "mechanism": "Binds the IL-23 receptor with a dissociation constant of 7 pM and antagonises IL-23 binding, inhibiting IL-23-dependent release of pro-inflammatory cytokines (Icotyde label, section 12.1).", "primaryUses": [ "Moderate-to-severe plaque psoriasis in adults and children 12+ weighing at least 40 kg (FDA-approved)" ], "typicalDose": { "range": "200", "unit": "mg", "frequency": "once daily, on waking, on an empty stomach", "route": "oral", "notes": "Label: take with water and wait at least 30 minutes before eating; the tablet can be dispersed in water." }, "related": [ "kpv", "ll-37", "enlicitide", "semaglutide" ] }, { "id": "ideglira", "name": "Insulin degludec / liraglutide (IDegLira)", "aliases": [ "Xultophy", "Xultophy 100/3.6", "IDegLira" ], "tier": "mid", "category": "metabolic", "subcategory": "fixed-ratio insulin / GLP-1 combination", "class": "A fixed-ratio combination of the ultra-long-acting basal insulin analog degludec and the GLP-1 receptor agonist liraglutide in a single injection pen.", "tagline": "Insulin degludec and liraglutide in one daily pen at a fixed ratio: more HbA1c lowering than either alone, with a boxed thyroid warning.", "oneLiner": "A fixed-ratio combination of a long-acting insulin and a GLP-1 drug, so titrating one titrates both, sold as Xultophy 100/3.6.", "sequence": "Combination of two separate molecules (see insulin-degludec and liraglutide entries).", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": 25, "unit": "hours", "range": "about 25 hours (degludec) and 13 hours (liraglutide)", "notes": "Two molecules with different PK profiles co-administered.", "source": { "type": "label", "ref": "Xultophy 100/3.6 prescribing information, section 12.3 (DailyMed version 14, effective October 14, 2025; read September 30, 2026)" } }, "fdaStatus": "approved", "approvalDetails": "FDA-approved as Xultophy 100/3.6 (insulin degludec 100 U/mL and liraglutide 3.6 mg/mL), Novo Nordisk, with a boxed warning for thyroid C-cell tumours from its liraglutide component. Starting dose 10 or 16 units once daily, maximum 50 units.", "mechanism": "Dual mechanism: insulin degludec provides sustained basal insulin receptor agonism; liraglutide provides GLP-1 receptor agonism (glucose-dependent insulin secretion, glucagon suppression, delayed gastric emptying, central appetite suppression). The fixed-ratio pen delivers both at a constant ratio with each dose increment.", "primaryUses": [ "Glycaemic control in adults with type 2 diabetes (US label)" ], "typicalDose": { "range": "16–50", "unit": "dose units", "frequency": "once daily", "route": "subcutaneous", "notes": "1 dose unit = 1 unit degludec + 0.036 mg liraglutide. Max daily dose 50 units." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Xultophy 100/3.6 (insulin degludec and liraglutide) injection Prescribing Information, sections 1 and 2 (DailyMed version 14, effective October 14, 2025; read September 30, 2026)." }, { "type": "pubmed", "citation": "Gough SC, et al. \"Efficacy and safety of a fixed-ratio combination of insulin degludec and liraglutide (IDegLira) compared with its components given alone: results of a phase 3, open-label, randomised, 26-week, treat-to-target trial in insulin-naive patients with type 2 diabetes.\" Lancet Diabetes Endocrinol, 2014;2(11):885-93. PMID: 25190523.", "pmid": "25190523" }, { "type": "pubmed", "citation": "Rodbard HW, et al. \"Safety and efficacy of insulin degludec/liraglutide (IDegLira) added to sulphonylurea alone or to sulphonylurea and metformin in insulin-naïve people with Type 2 diabetes: the DUAL IV trial.\" Diabet Med, 2017;34(2):189-196. PMID: 27589252.", "pmid": "27589252" }, { "type": "pubmed", "citation": "Kaku K, et al. \"Superior efficacy with a fixed-ratio combination of insulin degludec and liraglutide (IDegLira) compared with insulin degludec and liraglutide in insulin-naïve Japanese patients with type 2 diabetes in a phase 3, open-label, randomized trial.\" Diabetes Obes Metab, 2019;21(12):2674-2683. PMID: 31407845.", "pmid": "31407845" }, { "type": "pubmed", "citation": "Pei Y, et al. \"DUAL II China: Superior HbA1c reductions and weight loss with insulin degludec/liraglutide (IDegLira) versus insulin degludec in a randomized trial of Chinese people with type 2 diabetes inadequately controlled on basal insulin.\" Diabetes Obes Metab, 2021;23(12):2687-2696. PMID: 34387411.", "pmid": "34387411" } ], "interactionCoverage": "label", "related": [ "insulin-degludec", "liraglutide", "iglarlixi" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S4.4.2", "named": false, "wording": "Insulins and insulin-mimetics", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Contains insulin degludec, prohibited as a class under S4.4.2; its liraglutide is not listed." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S4.4.2", "named": false, "wording": "Insulins and insulin-mimetics", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Contains insulin degludec, prohibited as a class under S4.4.2; its liraglutide is not listed." } ], "moleculeClass": "peptide" }, { "id": "igf-1", "name": "IGF-1", "aliases": [ "Insulin-like Growth Factor 1", "Somatomedin C", "IGF-I" ], "tier": "mid", "category": "growth-hormone", "subcategory": "Endogenous growth factor", "class": "IGF-1 is the primary mediator of growth hormone's anabolic effects — the peptide that actually builds tissue when GH stimulates its production in the liver. Parent molecule to IGF-1 LR3 and IGF-1 DES already in the encyclopedia.", "tagline": "The growth factor behind growth hormone: given as Increlex to children who cannot make it, and in adults a level whose extremes both track risk.", "oneLiner": "A growth factor released mainly in response to growth hormone; recombinant IGF-1 (mecasermin, Increlex) treats severe primary IGF-1 deficiency.", "sequence": "GPETLCGAELVDALQFVCGDRGFYFNKPTGYGSSSRRAPQTGIVDECCFRSCDLRRLEMYCAPLKPAKSA (70 aa, 3 disulfide bonds)", "molecularFormula": "C331H512N94O101S7", "molecularWeight": 7649.0, "halfLife": { "value": 5.8, "unit": "hours", "range": "5.8 hours after a subcutaneous dose (children)", "source": { "type": "label", "ref": "Increlex prescribing information, section 12.3 (DailyMed version 5, effective May 18, 2026; read September 30, 2026)" } }, "fdaStatus": "approved", "approvalDetails": "FDA-approved as Increlex (mecasermin), BLA 021839, for growth failure in children 2 years and older with severe primary IGF-1 deficiency or growth hormone gene deletion with neutralising antibodies; 0.04-0.08 mg/kg twice daily, up to 0.12 mg/kg, given within 20 minutes of a meal or snack. Not a substitute for growth hormone.", "mechanism": "Binds IGF-1R (receptor tyrosine kinase), triggering PI3K/Akt/mTOR (protein synthesis, cell survival) and RAS/MAPK (cell proliferation) pathways. In bone: chondrocyte and osteoblast stimulation. In muscle: myofibrillar protein synthesis and satellite cell activation. Circulating IGF-1 provides negative feedback to hypothalamic GH release.", "primaryUses": [ "Growth failure from severe primary IGF-1 deficiency (Increlex)", "Biomarker of growth hormone activity" ], "typicalDose": { "range": "40-120", "unit": "mcg/kg", "frequency": "twice daily (with meals)", "route": "subcutaneous", "notes": "Mecasermin: 40 mcg/kg SC twice daily, titrated to 120 mcg/kg. Must be taken with meals (hypoglycemia risk). Black box warning." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "INCRELEX (mecasermin) injection Prescribing Information, sections 1, 2 and 12.3 (DailyMed version 5, effective May 18, 2026; read September 30, 2026)." }, { "type": "pubmed", "citation": "Chernausek SD, et al. \"Long-term treatment with recombinant insulin-like growth factor (IGF)-I in children with severe IGF-I deficiency due to growth hormone insensitivity.\" J Clin Endocrinol Metab, 2007;92(3):902-10. PMID: 17192294.", "pmid": "17192294" }, { "type": "pubmed", "citation": "Zhang WB, et al. \"The antagonistic pleiotropy of insulin-like growth factor 1.\" Aging Cell, 2021;20(9):e13443. PMID: 34363732.", "pmid": "34363732" }, { "type": "pubmed", "citation": "Laron Z. \"Insulin-like growth factor 1 (IGF-1): a growth hormone.\" Mol Pathol, 2001;54(5):311-6. PMID: 11577173.", "pmid": "11577173" }, { "type": "pubmed", "citation": "Higashi Y, et al. \"IGF-1 and cardiovascular disease.\" Growth Horm IGF Res, 2019;45:6-16. PMID: 30735831.", "pmid": "30735831" }, { "type": "other", "citation": "US FDA, Drugs@FDA (openFDA): INCRELEX (mecasermin), BLA 021839, prescription. Read September 30, 2026." } ], "interactionCoverage": "partial", "related": [ "igf-1-lr3", "igf-1-des", "somatropin", "mecasermin", "mgf" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-21", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.3", "named": true, "wording": "Insulin-like growth factor 1 (IGF-1, mecasermin) and its analogues", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.3", "named": true, "wording": "Insulin-like growth factor 1 (IGF-1, mecasermin) and its analogues", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "igf-1-des", "name": "IGF-1 DES(1-3)", "aliases": [ "DES(1-3) IGF-1", "DES IGF-1", "des1-3 IGF-1" ], "tier": "stub", "category": "research", "subcategory": "IGF-1 analog", "class": "A truncated IGF-1 analog missing the first three N-terminal residues (Gly-Pro-Glu).", "tagline": "Deleting the first three amino acids of IGF-1 cripples IGFBP binding while preserving receptor activity — giving DES(1-3) roughly 10× the in vitro potency of native IGF-1 at promoting cell growth in IGFBP-rich environments.", "oneLiner": "A naturally occurring IGF-1 variant (first identified in bovine colostrum and human brain tissue) lacking the Gly-Pro-Glu N-terminal tripeptide, which binds IGF-1R normally but has dramatically reduced affinity for the IGF-binding proteins that normally sequester IGF-1 in circulation.", "sequence": "TLCGAELVDALQFVCGDRGFYFNKPTGYGSSSRRAPQTGIVDECCFRSCDLRRLEMYCAPLKPAKSA", "molecularFormula": null, "molecularWeight": 7372, "halfLife": { "value": null, "unit": null, "range": "minutes to low hours", "notes": "Shorter systemic persistence than LR3; local/tissue action is the relevant kinetic parameter in most research contexts." }, "fdaStatus": "research-only", "approvalDetails": "Not approved. Research reagent only. Unlike LR3, DES(1-3) occurs endogenously in small quantities and was not deliberately engineered.", "mechanism": "Binds IGF-1R with similar affinity to native IGF-1 but with ~10-fold reduced binding to IGFBP-3, the dominant serum IGFBP. In IGFBP-rich environments — which is essentially all extracellular human biology — DES(1-3) is therefore substantially more bioavailable at the receptor. Downstream signaling (PI3K/Akt/mTOR and MAPK) is identical to native IGF-1.", "primaryUses": [ "Research reagent for IGF-1 bioavailability studies", "Cell culture growth media", "Community bodybuilding use (unapproved, no safety data)" ], "typicalDose": { "range": "research-only", "unit": "", "frequency": "varies", "route": "subcutaneous (community)", "notes": "No human clinical dosing standard. Community use carries the same hypoglycemia and theoretical cancer-promotion concerns as LR3, with even less pharmacokinetic data to guide dosing." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Ballard FJ, et al. \"Des(1-3)IGF-I: a truncated form of insulin-like growth factor-I.\" Int J Biochem Cell Biol, 1996;28:1085-1087. PMID: 8930132.", "pmid": "8930132" }, { "type": "pubmed", "citation": "Francis GL, et al. \"Insulin-like growth factor (IGF)-I and IGF-II which partially lack N-terminal amino acids have reduced affinity for IGF-binding proteins.\" J Mol Endocrinol, 1992;8:213-223." } ], "interactionCoverage": "unreviewed", "related": [ "igf-1-lr3", "peg-mgf", "mgf", "somatropin" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.3", "named": false, "wording": "Insulin-like growth factor 1 (IGF-1, mecasermin) and its analogues", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "A truncated IGF-1 that also occurs naturally in small amounts." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.3", "named": false, "wording": "Insulin-like growth factor 1 (IGF-1, mecasermin) and its analogues", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "A truncated IGF-1 that also occurs naturally in small amounts." } ], "moleculeClass": "peptide" }, { "id": "igf-1-lr3", "name": "IGF-1 LR3", "aliases": [ "Long R3 IGF-1", "Long Arg3 IGF-1", "LR3 IGF-1" ], "tier": "full", "category": "research", "subcategory": "IGF-1 analog", "class": "An 83-amino-acid analogue of insulin-like growth factor 1 with a 13-residue N-terminal extension and arginine at position 3, which together nearly abolish binding to IGF-binding proteins.", "tagline": "IGF-1 rebuilt so its binding proteins barely hold it: more potent than IGF-1 in rats, cleared faster, and never given to a person in a published study.", "oneLiner": "A recombinant 83-residue IGF-1 analogue (Long [Arg3]-IGF-I, 1992) that activates IGF-1 receptors while largely escaping IGF-binding proteins; studied in rats, calves and fetal sheep, never in people.", "sequence": "MFPAMPLSSLFVNGPRTLCGAELVDALQFVCGDRGFYFNKPTGYGSSSRRAPQTGIVDECCFRSCDLRRLEMYCAPLKPAKSA", "molecularFormula": "C400H619N111O115S9", "molecularWeight": 9111.6, "halfLife": { "value": null, "unit": "hours", "range": "Not measured in people; rats clear it faster than IGF-1", "notes": "Because IGF-binding proteins barely hold it, rats cleared it from the circulation faster than IGF-1 (1996), and after one intramuscular dose in rats the intact peptide was undetectable after 4 hours (2021). The '~6 hours (rat)' figure in our earlier entry had no source." }, "fdaStatus": "research-only", "approvalDetails": "Not approved for human use anywhere, and no published study has given it to a person. Recombinant human IGF-1 (mecasermin, Increlex) is FDA-approved for severe primary IGF-1 deficiency; IGF-1 LR3 is a different molecule.", "mechanism": "Activates the IGF-1 receptor while IGF-binding proteins barely bind it, so more of each dose is free to act: infused in rats it was 1.5–2 times as potent as IGF-1, and it is cleared faster. In animals it lowered blood glucose and insulin (calves, fetal sheep) and enlarged the gut, kidneys, spleen and adrenals without increasing body growth (guinea pigs).", "primaryUses": [ "Laboratory reagent for IGF-1 signalling without binding-protein interference", "Animal research on growth, the gut, lactation, fetal growth and nerve repair", "Unapproved bodybuilding use (no human data)" ], "typicalDose": { "range": "research-only", "unit": "", "frequency": "varies", "route": "subcutaneous (community)", "notes": "No human dose has been studied. Community protocols (20–100 µg/day) rest on no trial; in animals it lowered blood glucose, and IGF-1 signalling drives some cancer cells." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Conlon MA, et al. \"Long R3 insulin-like growth factor-I (IGF-I) infusion stimulates organ growth but reduces plasma IGF-I, IGF-II and IGF binding protein concentrations in the guinea pig.\" J Endocrinol, 1995;146(2):247-53. PMID: 7561636.", "pmid": "7561636" }, { "type": "pubmed", "citation": "Bryant KJ, et al. \"Design and characterisation of long-R3-insulin-like growth factor-I muteins which show resistance to pepsin digestion.\" Growth Factors, 1996;13(3-4):261-72. PMID: 8919033.", "pmid": "8919033" }, { "type": "pubmed", "citation": "Hammon H, et al. \"The somatotropic axis in neonatal calves can be modulated by nutrition, growth hormone, and Long-R3-IGF-I.\" Am J Physiol, 1997;273(1 Pt 1):E130-8. PMID: 9252489.", "pmid": "9252489" }, { "type": "pubmed", "citation": "Hammon H, et al. \"Endocrine and metabolic changes in neonatal calves in response to growth hormone and long-R3-insulin-like growth factor-I administration.\" Biol Neonate, 1998;73(2):121-8. PMID: 9483305.", "pmid": "9483305" }, { "type": "pubmed", "citation": "Bühler C, et al. \"Small intestinal morphology in eight-day-old calves fed colostrum for different durations or only milk replacer and treated with long-R3-insulin-like growth factor I and growth hormone.\" J Anim Sci, 1998;76(3):758-65. PMID: 9535335.", "pmid": "9535335" }, { "type": "pubmed", "citation": "Staley MD, et al. \"Rat milk and dietary long arginine3 insulin-like growth factor I promote intestinal growth of newborn rat pups.\" Pediatr Res, 1998;44(4):512-8. PMID: 9773839.", "pmid": "9773839" }, { "type": "pubmed", "citation": "Garnaut SM, et al. \"Effects of insulin-like growth factor-I and its analogue, long-R3-IGF-I, on intestinal absorption of 3-O-methyl-D-glucose are less pronounced than gut mucosal growth responses.\" Growth Factors, 2002;20(1):17-25. PMID: 11999215.", "pmid": "11999215" }, { "type": "pubmed", "citation": "Xi G, et al. \"Effect of recombinant porcine IGFBP-3 on IGF-I and long-R3-IGF-I-stimulated proliferation and differentiation of L6 myogenic cells.\" J Cell Physiol, 2004;200(3):387-94. PMID: 15254966.", "pmid": "15254966" }, { "type": "pubmed", "citation": "Hadsell DL, et al. \"Enhancement of maternal lactation performance during prolonged lactation in the mouse by mouse GH and long-R3-IGF-I is linked to changes in mammary signaling and gene expression.\" J Endocrinol, 2008;198(1):61-70. PMID: 18577570.", "pmid": "18577570" }, { "type": "pubmed", "citation": "Mongongu C, et al. \"Detection of LongR(3) -IGF-I, Des(1-3)-IGF-I, and R(3) -IGF-I using immunopurification and high resolution mass spectrometry for antidoping purposes.\" Drug Test Anal, 2021;13(7):1256-1269. PMID: 33587816.", "pmid": "33587816" }, { "type": "pubmed", "citation": "White A, et al. \"Attenuated glucose-stimulated insulin secretion during an acute IGF-1 LR3 infusion into fetal sheep does not persist in isolated islets.\" J Dev Orig Health Dis, 2023;14(3):353-361. PMID: 37114757.", "pmid": "37114757" }, { "type": "pubmed", "citation": "Lu Z, et al. \"Recombinant expression of IGF-1 and LR3 IGF-1 fused with xylanase in Pichia pastoris.\" Appl Microbiol Biotechnol, 2023;107(14):4543-4551. PMID: 37261455.", "pmid": "37261455" }, { "type": "pubmed", "citation": "Engel MG, et al. \"Intranasal long R3 insulin-like growth factor-1 treatment promotes amyloid plaque remodeling in cerebral cortex but fails to preserve cognitive function in male 5XFAD mice.\" J Alzheimers Dis, 2025;103(1):113-126. PMID: 39610283.", "pmid": "39610283" }, { "type": "pubmed", "citation": "White A, et al. \"IGF-1 LR3 does not promote growth in late-gestation growth-restricted fetal sheep.\" Am J Physiol Endocrinol Metab, 2025;328(1):E116-E125. PMID: 39679943.", "pmid": "39679943" }, { "type": "pubmed", "citation": "Yavuz E, et al. \"Revolutionary decellularized Alstroemeria stem-based nerve conduit integrated with GelMA and controlled IGF-1 LR3 release for enhanced rat sciatic nerve regeneration.\" Int J Biol Macromol, 2025;329(Pt 2):147888. PMID: 41015370.", "pmid": "41015370" }, { "type": "pubmed", "citation": "Francis GL, et al. \"Novel recombinant fusion protein analogues of insulin-like growth factor (IGF)-I indicate the relative importance of IGF-binding protein and receptor binding for enhanced biological potency.\" J Mol Endocrinol, 1992;8(3):213-23. PMID: 1378742.", "pmid": "1378742" }, { "type": "pubmed", "citation": "Tomas FM, et al. \"Anabolic effects of insulin-like growth factor-I (IGF-I) and an IGF-I variant in normal female rats.\" J Endocrinol, 1993;137(3):413-21. PMID: 8371075.", "pmid": "8371075" }, { "type": "pubmed", "citation": "Tomas FM, et al. \"Superior potency of infused IGF-I analogues which bind poorly to IGF-binding proteins is maintained when administered by injection.\" J Endocrinol, 1996;150(1):77-84. PMID: 8708565.", "pmid": "8708565" }, { "type": "pubmed", "citation": "Stremming J, et al. \"IGF-1 infusion to fetal sheep increases organ growth but not by stimulating nutrient transfer to the fetus.\" Am J Physiol Endocrinol Metab, 2021;320(3):E527-E538. PMID: 33427051.", "pmid": "33427051" }, { "type": "pubmed", "citation": "Vink-van Wijngaarden T, et al. \"Inhibition of insulin- and insulin-like growth factor-I-stimulated growth of human breast cancer cells by 1,25-dihydroxyvitamin D3 and the vitamin D3 analogue EB1089.\" Eur J Cancer, 1996;32A(5):842-8. PMID: 9081364.", "pmid": "9081364" }, { "type": "fda-pi", "citation": "Increlex (mecasermin [rDNA origin]) Prescribing Information. Ipsen Biopharmaceuticals. (Reference: native IGF-1, not LR3.)" } ], "interactionCoverage": "partial", "related": [ "igf-1-des", "peg-mgf", "mgf", "somatropin", "cjc-1295", "ipamorelin" ], "lastReviewed": "2026-09-27", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.3", "named": false, "wording": "Insulin-like growth factor 1 (IGF-1, mecasermin) and its analogues", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.3", "named": false, "wording": "Insulin-like growth factor 1 (IGF-1, mecasermin) and its analogues", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "protein", "moleculeClassBasis": "83-amino-acid" }, { "id": "iglarlixi", "name": "Insulin glargine / lixisenatide (iGlarLixi)", "aliases": [ "Soliqua", "Soliqua 100/33", "Suliqua", "iGlarLixi" ], "tier": "mid", "category": "metabolic", "subcategory": "fixed-ratio insulin / GLP-1 combination", "class": "A fixed-ratio combination of insulin glargine and the short-acting GLP-1 agonist lixisenatide in a single injection pen.", "tagline": "Sanofi's fixed-ratio insulin/GLP-1 combo pen (Soliqua, FDA 2016) — 100 units/mL insulin glargine + 33 mcg/mL lixisenatide; a parallel to Xultophy, differentiated by using short-acting prandial-biased lixisenatide rather than liraglutide.", "oneLiner": "A fixed-ratio combination pen of insulin glargine (100 units/mL) and lixisenatide (33 mcg/mL) administered once daily, FDA-approved as Soliqua in 2016 (marketed as Suliqua in the EU); the lixisenatide component contributes prandial glucose control via its short-acting gastric-emptying-slowing effects, making this combination prandial-biased in contrast with the basal-biased Xultophy (IDegLira).", "sequence": "Combination of two separate molecules (see insulin-glargine and lixisenatide entries).", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": 3, "unit": "hours", "range": "about 3 hours for lixisenatide (terminal)", "notes": "Two molecules, so no single value; insulin glargine is a once-daily basal insulin.", "source": { "type": "label", "ref": "Soliqua 100/33 prescribing information, section 12.3 (DailyMed version 25, effective March 18, 2026; read September 30, 2026)" } }, "fdaStatus": "approved", "approvalDetails": "FDA: SOLIQUA 100/33 (insulin glargine and lixisenatide injection), BLA 208673 (Sanofi), approved November 21, 2016 (Drugs@FDA), as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes; label effective March 18, 2026. EU: authorised as Suliqua.", "mechanism": "Dual mechanism: insulin glargine provides 24-hour basal insulin coverage; lixisenatide provides prandial-biased GLP-1 agonism — because of its short half-life and once-daily dosing before the largest meal, lixisenatide most effectively controls postprandial glucose for that meal.", "primaryUses": [ "Type 2 diabetes mellitus inadequately controlled on basal insulin or GLP-1 monotherapy" ], "typicalDose": { "range": "15–60", "unit": "dose units", "frequency": "once daily before first meal", "route": "subcutaneous", "notes": "1 dose unit = 1 unit glargine + 0.33 mcg lixisenatide. Max 60 units daily." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Sanofi-Aventis U.S. SOLIQUA 100/33 (insulin glargine and lixisenatide injection), US prescribing information: indication, dosing (15-60 units once daily, maximum 60 units), limitations of use, lixisenatide half-life about 3 hours. DailyMed version effective March 18, 2026; read September 30, 2026." }, { "type": "pubmed", "citation": "Rosenstock J, et al. \"Efficacy and Safety of LixiLan, a Titratable Fixed-Ratio Combination of Lixisenatide and Insulin Glargine, Versus Insulin Glargine in Type 2 Diabetes Inadequately Controlled on Metformin Monotherapy: The LixiLan Proof-of-Concept Randomized Trial.\" Diabetes Care, 2016;39(9):1579-86. PMID: 27284114.", "pmid": "27284114" }, { "type": "pubmed", "citation": "Rosenstock J, et al. \"Advancing Therapy in Suboptimally Controlled Basal Insulin-Treated Type 2 Diabetes: Clinical Outcomes With iGlarLixi Versus Premix BIAsp 30 in the SoliMix Randomized Controlled Trial.\" Diabetes Care, 2021;44(10):2361-70. PMID: 34183429.", "pmid": "34183429" }, { "type": "pubmed", "citation": "Yuan X, et al. \"Improved glycaemic control and weight benefit with iGlarLixi versus insulin glargine 100 U/mL in Chinese people with type 2 diabetes advancing their therapy from basal insulin plus oral antihyperglycaemic drugs: Results from the LixiLan-L-CN randomized controlled trial.\" Diabetes Obes Metab, 2022;24(11):2182-2191. PMID: 35762489.", "pmid": "35762489" }, { "type": "pubmed", "citation": "Liu M, et al. \"The efficacy and safety of iGlarLixi versus IDegAsp in Chinese people with type 2 diabetes suboptimally controlled with oral antidiabetic drugs: The Soli-D randomized controlled trial.\" Diabetes Obes Metab, 2024;26(9):3791-3800. PMID: 38922731.", "pmid": "38922731" }, { "type": "pubmed", "citation": "Novodvorský P, et al. \"Insulin therapy DE-intensificAtion with iGlarLixi: A phase 4, open-label, parallel-group randomised controlled trial.\" Diabetes Obes Metab, 2026;28(3):1817-1825. PMID: 41395661.", "pmid": "41395661" }, { "type": "fda", "citation": "FDA. Drugs@FDA (openFDA): SOLIQUA 100/33, BLA 208673, approved November 21, 2016. Read September 30, 2026." } ], "interactionCoverage": "label", "related": [ "insulin-glargine", "lixisenatide", "ideglira" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S4.4.2", "named": false, "wording": "Insulins and insulin-mimetics", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Contains insulin glargine, prohibited as a class under S4.4.2; its lixisenatide is not listed." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S4.4.2", "named": false, "wording": "Insulins and insulin-mimetics", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Contains insulin glargine, prohibited as a class under S4.4.2; its lixisenatide is not listed." } ], "moleculeClass": "peptide" }, { "id": "insulin-aspart", "name": "Insulin aspart", "aliases": [ "NovoLog", "NovoRapid", "Fiasp", "Kirsty" ], "tier": "full", "category": "metabolic", "subcategory": "rapid-acting insulin analog", "class": "A rapid-acting recombinant human insulin analog with proline at B28 replaced by aspartic acid.", "tagline": "Novo Nordisk's rapid-acting insulin analogue (NovoLog / NovoRapid, approved 2000): one amino-acid change at B28 brings its peak to 40–50 minutes after injection, against 80–120 for regular human insulin. Fiasp (2017) adds niacinamide and L-arginine for faster early absorption, and US biosimilars followed from 2025.", "oneLiner": "A rapid-acting recombinant human insulin analogue (NovoLog in the US, NovoRapid elsewhere; Novo Nordisk; FDA-approved June 7, 2000) in which the proline at B28 is replaced by aspartic acid. It is absorbed faster than regular human insulin, peaking 40 to 50 minutes after subcutaneous injection, and is given 5 to 10 minutes before meals, by pump, or intravenously under supervision. Fiasp (approved September 29, 2017) is the same insulin with niacinamide and L-arginine added, which speed initial absorption; biosimilars Merilog (2025), Kirsty (2025) and Garzulys (2026) are also FDA-approved.", "sequence": "A chain GIVEQCCTSICSLYQLENYCN; B chain FVNQHLCGSHLVEALYLVCGERGFFYTDKT (Asp at B28 in place of human insulin's Pro); three disulfide bonds", "molecularFormula": "C256H381N65O79S6", "molecularWeight": 5825.8, "halfLife": { "value": 81, "unit": "minutes", "range": "apparent half-life 81 minutes after subcutaneous injection (NovoLog label)", "notes": "Median time to peak concentration 40 to 50 minutes, against 80 to 120 minutes for regular human insulin (NovoLog label, section 12.3)." }, "fdaStatus": "approved", "approvalDetails": "FDA: NovoLog (BLA 020986), approved June 7, 2000; Fiasp (BLA 208751), September 29, 2017; biosimilars Merilog (insulin aspart-szjj, BLA 761325), February 14, 2025, Kirsty (BLA 761188), July 15, 2025, and Garzulys (BLA 761497), July 24, 2026 (Drugs@FDA, read September 30, 2026). EU: NovoRapid, Fiasp and biosimilars authorised centrally.", "mechanism": "Insulin receptor agonist with the same actions as human insulin: it stimulates glucose uptake by muscle and fat and suppresses hepatic glucose output. Replacing proline B28 with aspartic acid speeds absorption from subcutaneous tissue, so serum concentrations rise and fall sooner than with regular human insulin. In Fiasp, niacinamide and L-arginine accelerate initial absorption further (onset of appearance about 3 minutes; up to 2.5-fold greater glucose-lowering in the first 30 minutes).", "primaryUses": [ "Type 1 diabetes mellitus (mealtime bolus)", "Type 2 diabetes mellitus requiring prandial insulin", "Insulin pump therapy (CSII)" ], "typicalDose": { "range": null, "unit": "units", "frequency": "with meals", "route": "subcutaneous, pump or IV", "notes": "Fully individualised, as with all mealtime insulins; injected 5 to 10 minutes before a meal (NovoLog label)." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Novo Nordisk. NOVOLOG (insulin aspart) injection, US prescribing information: B28 proline-to-aspartic acid substitution, formula C256H381N65O79S6 and molecular weight 5825.8 Da (section 11); median time to peak 40 to 50 minutes vs 80 to 120 for regular human insulin and apparent half-life 81 minutes (section 12.3); hypoglycemia, hypokalemia, hypersensitivity and TZD fluid retention (section 5). DailyMed version effective February 28, 2023, read September 30, 2026." }, { "type": "pubmed", "citation": "Simpson KL, et al. \"Insulin aspart.\" Drugs, 1999;57(5):759-65; discussion 766-7. PMID: 10353301.", "pmid": "10353301" }, { "type": "pubmed", "citation": "Owens D, et al. \"Insulin aspart: a review.\" Expert Opin Drug Metab Toxicol, 2006;2(5):793-804. PMID: 17014395.", "pmid": "17014395" }, { "type": "pubmed", "citation": "Biester T, et al. \"Pharmacological Properties of Faster-Acting Insulin Aspart.\" Curr Diab Rep, 2017;17(11):101. PMID: 28940145.", "pmid": "28940145" }, { "type": "pubmed", "citation": "Haahr H, et al. \"Fast-Acting Insulin Aspart: A Review of its Pharmacokinetic and Pharmacodynamic Properties and the Clinical Consequences.\" Clin Pharmacokinet, 2020;59(2):155-172. PMID: 31667789.", "pmid": "31667789" }, { "type": "pubmed", "citation": "Hövelmann U, et al. \"Pharmacokinetic Properties of Fast-Acting Insulin Aspart Administered in Different Subcutaneous Injection Regions.\" Clin Drug Investig, 2017;37(5):503-509. PMID: 28185141.", "pmid": "28185141" }, { "type": "pubmed", "citation": "Nørgaard SK, et al. \"Faster-acting insulin aspart versus insulin aspart in the treatment of type 1 or type 2 diabetes during pregnancy and post-delivery (CopenFast): an open-label, single-centre, randomised controlled trial.\" Lancet Diabetes Endocrinol, 2023;11(11):811-821. PMID: 37804858.", "pmid": "37804858" }, { "type": "pubmed", "citation": "Alexanian SM, et al. \"Comparing Postprandial Glycemic Control Using Fiasp vs Insulin Aspart in Hospitalized Patients With Type 2 Diabetes.\" Endocr Pract, 2025;31(3):306-314. PMID: 39643003.", "pmid": "39643003" }, { "type": "pubmed", "citation": "Ware J, et al. \"Hybrid Closed-Loop with Faster Insulin Aspart Compared with Standard Insulin Aspart in Very Young Children with Type 1 Diabetes: A Double-Blind, Multicenter, Randomized, Crossover Study.\" Diabetes Technol Ther, 2023;25(6):431-436. PMID: 36880866.", "pmid": "36880866" }, { "type": "pubmed", "citation": "Thrasher J, et al. \"Safety and Tolerability of Insulin Aspart Biosimilar SAR341402 Versus Originator Insulin Aspart (NovoLog) When Used in Insulin Pumps in Adults with Type 1 Diabetes: A Randomized, Open-Label Clinical Trial.\" Diabetes Technol Ther, 2020;22(9):666-673. PMID: 31833801.", "pmid": "31833801" }, { "type": "pubmed", "citation": "Blevins TC, et al. \"Immunogenicity, Efficacy, and Safety of Biosimilar Insulin Aspart (MYL-1601D) Compared with Originator Insulin Aspart (Novolog(®)) in Patients with Type 1 Diabetes After 24 Weeks: A Randomized Open-Label Study.\" BioDrugs, 2022;36(6):761-772. PMID: 36114990.", "pmid": "36114990" }, { "type": "pubmed", "citation": "McGuigan A. \"Insulin Aspart-szjj: An Insulin Aspart Biosimilar.\" Clin Drug Investig, 2026;46(3):353-357. PMID: 41572097.", "pmid": "41572097" }, { "type": "pubmed", "citation": "Brange J, et al. \"Monomeric insulins obtained by protein engineering and their medical implications.\" Nature, 1988;333(6174):679-82. PMID: 3287182.", "pmid": "3287182" }, { "type": "fda", "citation": "FDA. Drugs@FDA (openFDA): NovoLog BLA 020986 (approved June 7, 2000), Fiasp BLA 208751 (September 29, 2017), Merilog BLA 761325 (February 14, 2025), Kirsty BLA 761188 (July 15, 2025), Garzulys BLA 761497 (July 24, 2026). Read September 30, 2026." }, { "type": "other", "citation": "European Medicines Agency. Medicines register (centrally authorised human medicines): NovoRapid, Fiasp, Kirsty, Insulin aspart Sanofi, Dazparda and Maapliv authorised. Read September 30, 2026." } ], "interactionCoverage": "label", "related": [ "insulin-lispro", "insulin-glulisine", "insulin-regular" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S4.4.2", "named": false, "wording": "Insulins and insulin-mimetics", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Insulins are prohibited as a class; athletes with diabetes use them under a Therapeutic Use Exemption." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S4.4.2", "named": false, "wording": "Insulins and insulin-mimetics", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Insulins are prohibited as a class; athletes with diabetes use them under a Therapeutic Use Exemption." } ], "moleculeClass": "protein", "moleculeClassBasis": "insulin analog" }, { "id": "insulin-degludec", "name": "Insulin degludec", "aliases": [ "Tresiba", "Xultophy (combo)", "NN1250" ], "tier": "mid", "category": "metabolic", "subcategory": "ultra-long-acting basal insulin analog", "class": "An ultra-long-acting recombinant human insulin analog with threonine at B30 removed and a glutamic-acid-linked 16-carbon hexadecanedioic fatty acid attached at lysine B29.", "tagline": "Novo Nordisk's ultra-long-acting insulin (Tresiba, 2015) — forms soluble multi-hexamers in SC tissue that slowly dissociate for a >42-hour half-life and a flat, forgiving dosing window; the basal insulin with the lowest hypoglycemia risk profile.", "oneLiner": "An ultra-long-acting basal insulin analog (Tresiba, Novo Nordisk, FDA-approved 2015) engineered to self-assemble into soluble multi-hexamer chains in subcutaneous tissue via its hexadecanedioic-acid-glutamyl side chain — these slowly dissociate over days, producing a plasma half-life of approximately 25 hours and a clinical effect duration >42 hours, which translates into flat pharmacokinetics, flexible dosing windows, and the lowest rates of hypoglycemia among basal insulins in the SWITCH and DEVOTE trials.", "sequence": "Modified human insulin with des-Thr-B30 and γ-Glu-hexadecanedioyl-Lys(B29)", "molecularFormula": "C274H411N65O81S6", "molecularWeight": 6104, "halfLife": { "value": null, "unit": null, "range": "the label gives no half-life; after eight days of once-daily dosing in type 1 diabetes, peak concentration was reached at a median of 9 hours", "source": { "type": "label", "ref": "Tresiba (insulin degludec) prescribing information, sections 1, 2 and 12.3 (DailyMed SPL version 14, effective July 1, 2022; read October 1, 2026)" } }, "fdaStatus": "approved", "approvalDetails": "Tresiba, BLA 203314, approved September 25, 2015, to improve glycemic control in patients one year of age and older with diabetes mellitus; not recommended for diabetic ketoacidosis (Drugs@FDA and the label, read October 1, 2026).", "mechanism": "Insulin receptor agonism with pharmacokinetics driven by self-assembly into soluble multi-hexamer chains in the subcutaneous depot. Slow disassembly releases monomers over multiple days. The flat profile gives a uniquely forgiving dosing window — injections can be given at different times each day within an 8-to-40-hour range without loss of control.", "primaryUses": [ "Type 1 diabetes mellitus (basal)", "Type 2 diabetes mellitus (basal)" ], "typicalDose": { "range": null, "unit": null, "frequency": "once daily", "route": "subcutaneous", "notes": "Tresiba label: individualised, injected subcutaneously once daily into thigh, upper arm or abdomen, in adults at any time of day; rotate sites. For paediatric patients needing fewer than 5 units a day, use the U-100 vial." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Tresiba (insulin degludec) prescribing information, sections 1, 2 and 12.3 (DailyMed SPL version 14, effective July 1, 2022; read October 1, 2026)." }, { "type": "pubmed", "citation": "Marso SP, et al. \"Efficacy and Safety of Degludec versus Glargine in Type 2 Diabetes.\" N Engl J Med, 2017;377(8):723-732. PMID: 28605603.", "pmid": "28605603" }, { "type": "pubmed", "citation": "Lingvay I, et al. \"Once-Weekly Insulin Icodec vs Once-Daily Insulin Degludec in Adults With Insulin-Naive Type 2 Diabetes: The ONWARDS 3 Randomized Clinical Trial.\" JAMA, 2023;330(3):228-237. PMID: 37354562.", "pmid": "37354562" }, { "type": "pubmed", "citation": "Wysham C, et al. \"Insulin Efsitora versus Degludec in Type 2 Diabetes without Previous Insulin Treatment.\" N Engl J Med, 2024;391(23):2201-2211. PMID: 39254740.", "pmid": "39254740" }, { "type": "pubmed", "citation": "Gastaldelli A, et al. \"Effect of tirzepatide versus insulin degludec on liver fat content and abdominal adipose tissue in people with type 2 diabetes (SURPASS-3 MRI): a substudy of the randomised, open-label, parallel-group, phase 3 SURPASS-3 trial.\" Lancet Diabetes Endocrinol, 2022;10(6):393-406. PMID: 35468325.", "pmid": "35468325" }, { "type": "pubmed", "citation": "Jonassen I, et al. \"Design of the novel protraction mechanism of insulin degludec, an ultra-long-acting basal insulin.\" Pharm Res, 2012;29(8):2104-14. PMID: 22485010.", "pmid": "22485010" } ], "interactionCoverage": "label", "related": [ "insulin-glargine", "insulin-detemir", "insulin-icodec", "liraglutide" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S4.4.2", "named": false, "wording": "Insulins and insulin-mimetics", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Insulins are prohibited as a class; athletes with diabetes use them under a Therapeutic Use Exemption." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S4.4.2", "named": false, "wording": "Insulins and insulin-mimetics", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Insulins are prohibited as a class; athletes with diabetes use them under a Therapeutic Use Exemption." } ], "moleculeClass": "peptide" }, { "id": "insulin-detemir", "name": "Insulin detemir", "aliases": [ "Levemir", "NN304" ], "tier": "mid", "category": "metabolic", "subcategory": "long-acting basal insulin analog", "class": "A long-acting recombinant human insulin analog in which threonine at B30 is removed and a 14-carbon myristic acid is attached to lysine at B29.", "tagline": "Novo Nordisk's fatty-acid-acylated basal insulin (Levemir, 2005) — the myristoyl chain enables reversible albumin binding, extending the half-life; Novo Nordisk announced global discontinuation in December 2023 (US supply ended 2024).", "oneLiner": "A once- or twice-daily basal insulin analog (Levemir, Novo Nordisk, FDA-approved 2005) created by removing threonine from B30 and acylating lysine at B29 with a 14-carbon myristic acid; this fatty-acid tag enables reversible albumin binding that prolongs action to approximately 16–24 hours. Novo Nordisk announced global discontinuation in December 2023, with US commercial supply ending 2024 — a significant clinical event given Levemir's role in pregnancy-related diabetes.", "sequence": "Modified human insulin with des-Thr-B30 and myristoyl-Lys(B29)", "molecularFormula": "C267H402N64O76S6", "molecularWeight": 5917, "halfLife": { "value": null, "unit": null, "range": "not reported in the sources read", "source": { "type": "none", "note": "searched PubMed on October 1, 2026; no human half-life figure in the sources read" } }, "fdaStatus": "discontinued", "approvalDetails": "Levemir, BLA 021878, approved October 19, 2005 (Drugs@FDA, read October 1, 2026). Its manufacturer has announced discontinuation in the United States, so current availability should be checked.", "mechanism": "Insulin receptor agonism with action extended by reversible albumin binding via the myristic acid moiety — roughly 98% of circulating drug is albumin-bound, creating a slow-release reservoir. The remaining free fraction provides the pharmacologically active pool.", "primaryUses": [ "Type 1 diabetes mellitus (basal, historical)", "Type 2 diabetes mellitus (basal, historical)", "Gestational diabetes (notable — widely used in pregnancy before discontinuation)" ], "typicalDose": { "range": null, "unit": null, "frequency": "once or twice daily", "route": "subcutaneous", "notes": "Individualised basal insulin; in the head-to-head trial against glargine, 87.4% of detemir patients remained on once-daily dosing." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Raskin P, et al. \"Comparison of insulin detemir and insulin glargine using a basal-bolus regimen in a randomized, controlled clinical study in patients with type 2 diabetes.\" Diabetes Metab Res Rev, 2009;25(6):542-8. PMID: 19565569.", "pmid": "19565569" }, { "type": "pubmed", "citation": "Herrera KM, et al. \"Randomized controlled trial of insulin detemir versus NPH for the treatment of pregnant women with diabetes.\" Am J Obstet Gynecol, 2015;213(3):426.e1-7. PMID: 26070699.", "pmid": "26070699" }, { "type": "pubmed", "citation": "Mathiesen ER, et al. \"Insulin degludec versus insulin detemir, both in combination with insulin aspart, in the treatment of pregnant women with type 1 diabetes (EXPECT): an open‑label, multinational, randomised, controlled, non-inferiority trial.\" Lancet Diabetes Endocrinol, 2023;11(2):86-95. PMID: 36623517.", "pmid": "36623517" }, { "type": "pubmed", "citation": "Fishel Bartal M, et al. \"Detemir vs neutral protamine Hagedorn insulin for diabetes mellitus in pregnancy: a comparative effectiveness, randomized controlled trial.\" Am J Obstet Gynecol, 2021;225(1):87.e1-87.e10. PMID: 33865836.", "pmid": "33865836" }, { "type": "pubmed", "citation": "Swinnen SG, et al. \"Rationale, design, and baseline data of the insulin glargine (Lantus) versus insulin detemir (Levemir) Treat-To-Target (L2T3) study: A multinational, randomized noninferiority trial of basal insulin initiation in type 2 diabetes.\" Diabetes Technol Ther, 2009;11(11):739-43. PMID: 19905891.", "pmid": "19905891" }, { "type": "pubmed", "citation": "Havelund S, et al. \"The mechanism of protraction of insulin detemir, a long-acting, acylated analog of human insulin.\" Pharm Res, 2004;21(8):1498-504. PMID: 15359587.", "pmid": "15359587" }, { "type": "fda-pi", "citation": "FDA. Levemir (insulin detemir) prescribing information. Novo Nordisk." }, { "type": "manufacturer", "citation": "Novo Nordisk. Announcement: discontinuation of Levemir globally, December 2023." } ], "interactionCoverage": "label", "related": [ "insulin-glargine", "insulin-degludec", "insulin-nph" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S4.4.2", "named": false, "wording": "Insulins and insulin-mimetics", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Insulins are prohibited as a class; athletes with diabetes use them under a Therapeutic Use Exemption." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S4.4.2", "named": false, "wording": "Insulins and insulin-mimetics", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Insulins are prohibited as a class; athletes with diabetes use them under a Therapeutic Use Exemption." } ], "moleculeClass": "peptide" }, { "id": "insulin-efsitora", "name": "Insulin efsitora alfa", "aliases": [ "efsitora", "efsitora alfa", "LY3209590", "basal insulin Fc" ], "tier": "full", "category": "pipeline", "subcategory": "once-weekly basal insulin (approved 2026)", "class": "A once-weekly basal insulin analog in which a single-chain insulin variant is fused to an IgG2 Fc region via a peptide linker.", "tagline": "Lilly's once-weekly basal insulin, an insulin variant fused to an antibody Fc fragment, FDA-approved in September 2026 as Onswik for adults with type 2 diabetes after four QWINT trials found HbA1c lowering non-inferior to daily basal insulin.", "oneLiner": "A once-weekly basal insulin analog (Eli Lilly) constructed as a single-chain insulin variant fused to an IgG2 Fc region via a peptide linker — FcRn-mediated recycling and slow receptor-mediated clearance produce a plasma half-life of approximately 17 days. The Phase 3 QWINT program (five trials in T1DM and T2DM) read out in 2024 with non-inferior glycemic control versus daily basal analogs; NDA submission 2025 and FDA review ongoing.", "sequence": "Single-chain insulin analog fused to IgG2 Fc region via peptide linker", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": 408, "unit": "hours", "range": "~17 days", "notes": "About 17 days after single doses (phase 1) and 19 days at steady state (2026 clamp study); peak-to-trough ratio about 1.14 to 1.16." }, "fdaStatus": "approved", "approvalDetails": "FDA-approved as Onswik (insulin efsitora alfa-gobe; Eli Lilly; BLA 761408), original approval September 23, 2026 per Drugs@FDA, announced September 24, 2026, for adults with type 2 diabetes; not for type 1 diabetes. Lilly lists earlier approvals from the EMA, Japan's PMDA and Mexico's COFEPRIS.", "mechanism": "Insulin receptor agonism via a single-chain insulin analog engineered with reduced insulin receptor affinity and IgG2 Fc fusion. The Fc fusion provides FcRn-mediated recycling (the same half-life-extending mechanism used by monoclonal antibodies), while the attenuated receptor affinity slows receptor-mediated clearance. Together these produce ultra-long half-life and a flat PK profile.", "primaryUses": [ "Type 2 diabetes mellitus (Phase 3 complete)", "Type 1 diabetes mellitus (Phase 3 complete)" ], "typicalDose": { "range": null, "unit": "units", "frequency": "once weekly", "route": "subcutaneous", "notes": "QWINT program used flexible initiation/titration protocols. Typical T2DM weekly dose approximately 7× equivalent daily basal dose." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Rosenstock J, et al. \"Weekly Fixed-Dose Insulin Efsitora in Type 2 Diabetes without Previous Insulin Therapy.\" N Engl J Med, 2025;393(4):325-335. PMID: 40548694.", "pmid": "40548694" }, { "type": "pubmed", "citation": "Wysham C, et al. \"Insulin Efsitora versus Degludec in Type 2 Diabetes without Previous Insulin Treatment.\" N Engl J Med, 2024;391(23):2201-2211. PMID: 39254740.", "pmid": "39254740" }, { "type": "pubmed", "citation": "Philis-Tsimikas A, et al. \"Once-weekly insulin efsitora alfa versus once-daily insulin degludec in adults with type 2 diabetes currently treated with basal insulin (QWINT-3): a phase 3, randomised, non-inferiority trial.\" Lancet, 2025;405(10497):2279-2289. PMID: 40562047.", "pmid": "40562047" }, { "type": "pubmed", "citation": "Blevins T, et al. \"Once-weekly insulin efsitora alfa versus once-daily insulin glargine U100 in adults with type 2 diabetes treated with basal and prandial insulin (QWINT-4): a phase 3, randomised, non-inferiority trial.\" Lancet, 2025;405(10497):2290-2301. PMID: 40562048.", "pmid": "40562048" }, { "type": "pubmed", "citation": "Bergenstal RM, et al. \"Once-weekly insulin efsitora alfa versus once-daily insulin degludec in adults with type 1 diabetes (QWINT-5): a phase 3 randomised non-inferiority trial.\" Lancet, 2024;404(10458):1132-1142. PMID: 39270686.", "pmid": "39270686" }, { "type": "pubmed", "citation": "Kazda CM, et al. \"Novel Once-Weekly Basal Insulin Fc Achieved Similar Glycemic Control With a Safety Profile Comparable to Insulin Degludec in Patients With Type 1 Diabetes.\" Diabetes Care, 2023;46(5):1052-1059. PMID: 36920867.", "pmid": "36920867" }, { "type": "pubmed", "citation": "Frias J, et al. \"Safety and efficacy of once-weekly basal insulin Fc in people with type 2 diabetes previously treated with basal insulin: a multicentre, open-label, randomised, phase 2 study.\" Lancet Diabetes Endocrinol, 2023;11(3):158-168. PMID: 36758572.", "pmid": "36758572" }, { "type": "pubmed", "citation": "Heise T, et al. \"Pharmacokinetic and pharmacodynamic properties of the novel basal insulin Fc (insulin efsitora alfa), an insulin fusion protein in development for once-weekly dosing for the treatment of patients with diabetes.\" Diabetes Obes Metab, 2023;25(4):1080-1090. PMID: 36541037.", "pmid": "36541037" }, { "type": "pubmed", "citation": "Leohr J, et al. \"Characterisation of steady-state pharmacokinetics and glucodynamics of once-weekly insulin efsitora alfa in individuals with type 2 diabetes.\" Diabetes Obes Metab, 2026;28(5):4010-4018. PMID: 41725424.", "pmid": "41725424" }, { "type": "pubmed", "citation": "Heise T, et al. \"Frequency and Severity of Hypoglycemia Under Conditions of Increased Hypoglycemic Risk with Insulin Efsitora Alfa Versus Insulin Glargine Treatment in Participants with Type 2 Diabetes.\" Diabetes Ther, 2024;15(8):1785-1797. PMID: 38907935.", "pmid": "38907935" }, { "type": "pubmed", "citation": "Connery L, et al. \"Glycaemic Control According to the Final Insulin Dose Using an Innovative Fixed-Dose Titration of Weekly Insulin Efsitora in Insulin-Naïve Type 2 Diabetes.\" Diabetes Obes Metab, 2026;28(7):6217-6224. PMID: 42070786.", "pmid": "42070786" }, { "type": "pubmed", "citation": "Moyers JS, et al. \"Preclinical Characterization of LY3209590, a Novel Weekly Basal Insulin Fc-Fusion Protein.\" J Pharmacol Exp Ther, 2022;382(3):346-355. PMID: 35840338.", "pmid": "35840338" }, { "type": "pubmed", "citation": "Bergenstal RM, et al. \"Once-weekly insulin efsitora alfa: Design and rationale for the QWINT phase 3 clinical development programme.\" Diabetes Obes Metab, 2024;26(8):3020-3030. PMID: 38679838.", "pmid": "38679838" }, { "type": "pubmed", "citation": "Rosenstock J, et al. \"The Basis for Weekly Insulin Therapy: Evolving Evidence With Insulin Icodec and Insulin Efsitora Alfa.\" Endocr Rev, 2024;45(3):379-413. PMID: 38224978.", "pmid": "38224978" }, { "type": "fda", "citation": "FDA. Drugs@FDA (openFDA), BLA 761408: ONSWIK (insulin efsitora alfa-gobe), Eli Lilly and Co; original approval September 23, 2026; marketing status Prescription. Read September 30, 2026." }, { "type": "manufacturer", "citation": "Eli Lilly and Company. U.S. Food and Drug Administration (FDA) approves Lilly's Onswik (insulin efsitora alfa-gobe), a once-weekly basal insulin injection treatment for adults living with type 2 diabetes. Press release, September 24, 2026. Read September 30, 2026." }, { "type": "fda-pi", "citation": "Eli Lilly and Company. ONSWIK (insulin efsitora alfa-gobe) injection, US prescribing information, revised 09/2026 (ONS-0001-USPI-20260923), pi.lilly.com; not yet on DailyMed. Read September 30, 2026." } ], "interactionCoverage": "none-found", "related": [ "insulin-icodec", "insulin-degludec", "insulin-glargine" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S4.4.2", "named": false, "wording": "Insulins and insulin-mimetics", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Insulins are prohibited as a class; athletes with diabetes use them under a Therapeutic Use Exemption." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S4.4.2", "named": false, "wording": "Insulins and insulin-mimetics", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Insulins are prohibited as a class; athletes with diabetes use them under a Therapeutic Use Exemption." } ], "moleculeClass": "protein", "moleculeClassBasis": "single-chain insulin" }, { "id": "insulin-glargine", "name": "Insulin glargine", "aliases": [ "Lantus", "Basaglar", "Toujeo", "Semglee", "Rezvoglar" ], "tier": "mid", "category": "metabolic", "subcategory": "long-acting basal insulin analog", "class": "A long-acting recombinant human insulin analog with A21 asparagine → glycine and two arginine residues added to the C-terminus of the B-chain (positions B31 and B32).", "tagline": "The dominant once-daily basal insulin for two decades (Lantus, Sanofi, 2000) — the pI-shift design causes microprecipitation in subcutaneous tissue for a nearly peakless 24-hour absorption profile; Toujeo (U-300) is the same molecule at 3× concentration.", "oneLiner": "A once-daily basal insulin analog (Lantus, Sanofi, FDA-approved 2000) engineered to shift the isoelectric point to physiologic pH, causing the drug — soluble at pH 4 in the vial — to microprecipitate after SC injection at pH 7.4, producing slow, nearly peakless 24-hour absorption; available as Lantus (U-100), Toujeo (U-300), and biosimilars Basaglar, Semglee, and Rezvoglar.", "sequence": "Modified human insulin with A21 Gly and B30 extended by Arg-Arg", "molecularFormula": "C267H404N72O78S6", "molecularWeight": 6063, "halfLife": { "value": null, "unit": null, "range": "the label gives no half-life; absorption is slower and more prolonged than NPH, with a relatively constant profile over 24 hours and no pronounced peak", "source": { "type": "label", "ref": "Lantus (insulin glargine) prescribing information, sections 1, 2, 4, 5, 6 and 12.3 (DailyMed SPL version 35, effective June 2, 2025; read October 1, 2026)" } }, "fdaStatus": "approved", "approvalDetails": "Lantus, BLA 021081, approved April 20, 2000; Toujeo, BLA 206538, February 25, 2015; Basaglar, BLA 205692, December 16, 2015; Semglee, BLA 210605, June 11, 2020, with the interchangeable version under BLA 761201 on July 28, 2021 (Drugs@FDA, read October 1, 2026). Indicated to improve glycemic control in adults and children with diabetes; not recommended for diabetic ketoacidosis.", "mechanism": "Insulin receptor agonism with a unique absorption profile driven by pI engineering. The addition of two C-terminal arginines to the B-chain shifts the isoelectric point from ~5.4 to ~6.7; the drug is formulated as a soluble acidic (pH 4) solution but precipitates into microcrystals on contact with subcutaneous tissue at pH 7.4, then slowly redissolves to deliver monomers over ~24 hours.", "primaryUses": [ "Type 1 diabetes mellitus (basal)", "Type 2 diabetes mellitus (basal)" ], "typicalDose": { "range": null, "unit": null, "frequency": "once daily, at the same time each day", "route": "subcutaneous", "notes": "The Lantus label sets no fixed dose: it is individualised to metabolic need, glucose monitoring, type of diabetes and prior insulin use. It is injected into the abdomen, thigh or upper arm, sites rotated, and must not be diluted or mixed with another insulin." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Lantus (insulin glargine) prescribing information, sections 1, 2, 4, 5, 6 and 12.3 (DailyMed SPL version 35, effective June 2, 2025; read October 1, 2026)." }, { "type": "pubmed", "citation": "Rosenstock J, et al. \"Basal insulin therapy in type 2 diabetes: 28-week comparison of insulin glargine (HOE 901) and NPH insulin.\" Diabetes Care, 2001;24(4):631-6. PMID: 11315821.", "pmid": "11315821" }, { "type": "pubmed", "citation": "Aroda VR, et al. \"Efficacy and safety of once-weekly semaglutide versus once-daily insulin glargine as add-on to metformin (with or without sulfonylureas) in insulin-naive patients with type 2 diabetes (SUSTAIN 4): a randomised, open-label, parallel-group, multicentre, multinational, phase 3a trial.\" Lancet Diabetes Endocrinol, 2017;5(5):355-366. PMID: 28344112.", "pmid": "28344112" }, { "type": "pubmed", "citation": "Pitlick JM, et al. \"Real-World Evaluation of Dosing in Patients Converted From Insulin Glargine (Lantus) to Insulin Glargine (Basaglar).\" Ann Pharmacother, 2020;54(9):846-851. PMID: 32037850.", "pmid": "32037850" }, { "type": "pubmed", "citation": "Wang W, et al. \"Immunogenicity of LY2963016 insulin glargine and Lantus® insulin glargine in Chinese patients with type 1 or type 2 diabetes mellitus.\" Diabetes Obes Metab, 2022;24(6):1094-1104. PMID: 35187770.", "pmid": "35187770" } ], "interactionCoverage": "label", "related": [ "insulin-nph", "insulin-detemir", "insulin-degludec", "insulin-icodec" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S4.4.2", "named": false, "wording": "Insulins and insulin-mimetics", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Insulins are prohibited as a class; athletes with diabetes use them under a Therapeutic Use Exemption." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S4.4.2", "named": false, "wording": "Insulins and insulin-mimetics", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Insulins are prohibited as a class; athletes with diabetes use them under a Therapeutic Use Exemption." } ], "moleculeClass": "peptide" }, { "id": "insulin-glulisine", "name": "Insulin glulisine", "aliases": [ "Apidra", "HMR1964" ], "tier": "mid", "category": "metabolic", "subcategory": "rapid-acting insulin analog", "class": "A rapid-acting recombinant human insulin analog with asparagine at B3 replaced by lysine and lysine at B29 replaced by glutamic acid.", "tagline": "Sanofi's rapid-acting insulin analog (Apidra, 2004) — the third rapid-acting analog approved, differentiated by being zinc-free in formulation, which gives it slightly faster monomeric onset than lispro or aspart.", "oneLiner": "A rapid-acting insulin analog (Apidra, Sanofi, FDA-approved 2004) with two B-chain substitutions — asparagine-B3 → lysine and lysine-B29 → glutamate — that together with a zinc-free polysorbate-20-stabilized formulation produce an absorption profile slightly faster than lispro or aspart, particularly in patients with higher BMI.", "sequence": "Modified human insulin with Lys(B3) / Glu(B29) substitutions", "molecularFormula": "C258H384N64O78S6", "molecularWeight": 5823, "halfLife": { "value": 42, "unit": "minutes", "range": "about 42 minutes after subcutaneous injection, against 86 minutes for regular insulin", "notes": "Apidra label, section 12.3.", "source": { "type": "label", "ref": "Apidra prescribing information, section 12.3 (DailyMed version 28, effective November 25, 2025; read September 30, 2026)" } }, "fdaStatus": "approved", "approvalDetails": "FDA: APIDRA (insulin glulisine injection), BLA 021629 (Sanofi), approved April 16, 2004 (Drugs@FDA), to improve glycemic control in adults and children with diabetes; label effective November 25, 2025.", "mechanism": "Insulin receptor agonism. The zinc-free formulation means the drug is already predominantly monomeric in the vial, so SC absorption is not limited by hexamer dissociation. The B3 and B29 charge changes stabilize the monomer against self-association even without zinc.", "primaryUses": [ "Type 1 diabetes mellitus (mealtime bolus)", "Type 2 diabetes mellitus requiring prandial insulin", "Insulin pump therapy (CSII)" ], "typicalDose": { "range": null, "unit": "units", "frequency": "with meals", "route": "subcutaneous or IV", "notes": "Fully individualized." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Sanofi. APIDRA (insulin glulisine injection), US prescribing information: indication, pharmacokinetics (subcutaneous half-life about 42 minutes vs 86 minutes for regular human insulin). DailyMed version effective November 25, 2025; read September 30, 2026." }, { "type": "pubmed", "citation": "Philotheou A, et al. \"Comparable efficacy and safety of insulin glulisine and insulin lispro when given as part of a Basal-bolus insulin regimen in a 26-week trial in pediatric patients with type 1 diabetes.\" Diabetes Technol Ther, 2011;13(3):327-34. PMID: 21291333.", "pmid": "21291333" }, { "type": "pubmed", "citation": "van Bon AC, et al. \"Insulin glulisine compared to insulin aspart and to insulin lispro administered by continuous subcutaneous insulin infusion in patients with type 1 diabetes: a randomized controlled trial.\" Diabetes Technol Ther, 2011;13(6):607-14. PMID: 21457066.", "pmid": "21457066" }, { "type": "pubmed", "citation": "Vora J, et al. \"Intensifying insulin regimen after basal insulin optimization in adults with type 2 diabetes: a 24-week, randomized, open-label trial comparing insulin glargine plus insulin glulisine with biphasic insulin aspart (LanScape).\" Diabetes Obes Metab, 2015;17(12):1133-41. PMID: 26085028.", "pmid": "26085028" }, { "type": "pubmed", "citation": "Drai R, et al. \"Immunogenicity, efficacy and safety of a biosimilar insulin glulisine compared with originator in adults with type 1 diabetes mellitus: A phase III randomised clinical trial.\" Diabetes Obes Metab, 2026;28(3):1791-1799. PMID: 41366610.", "pmid": "41366610" }, { "type": "fda", "citation": "FDA. Drugs@FDA (openFDA): APIDRA, BLA 021629, approved April 16, 2004. Read September 30, 2026." } ], "interactionCoverage": "label", "related": [ "insulin-lispro", "insulin-aspart", "insulin-regular" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S4.4.2", "named": false, "wording": "Insulins and insulin-mimetics", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Insulins are prohibited as a class; athletes with diabetes use them under a Therapeutic Use Exemption." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S4.4.2", "named": false, "wording": "Insulins and insulin-mimetics", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Insulins are prohibited as a class; athletes with diabetes use them under a Therapeutic Use Exemption." } ], "moleculeClass": "protein", "moleculeClassBasis": "insulin analog" }, { "id": "insulin-icodec", "name": "Insulin icodec", "aliases": [ "Awiqli", "NN1436" ], "tier": "mid", "category": "metabolic", "subcategory": "once-weekly basal insulin (approved 2026)", "class": "A once-weekly basal insulin analog with three amino acid substitutions (A14 Tyr→Glu, B16 Tyr→His, B25 Phe→His) and a C20 fatty diacid side chain at B29 conferring ultra-high albumin affinity.", "tagline": "The first once-weekly basal insulin: better HbA1c than daily insulin in type 2 diabetes, nearly double the serious hypos in type 1.", "oneLiner": "An albumin-binding basal insulin analogue injected once a week, approved as Awiqli for adults with type 2 diabetes.", "sequence": "Modified human insulin with A14E, B16H, B25H, des-Thr-B30, γ-Glu-C20-fatty-diacid-Lys(B29)", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": 7, "unit": "days", "range": "about one week after subcutaneous injection", "source": { "type": "label", "ref": "Awiqli prescribing information, section 12.3 (DailyMed version 1, effective March 26, 2026; read September 30, 2026)" } }, "fdaStatus": "approved", "approvalDetails": "FDA-approved March 26, 2026 as Awiqli (insulin icodec-abae), Novo Nordisk, BLA 761326, for glycaemic control in adults with type 2 diabetes; once weekly. Not approved for type 1 diabetes, where its phase 3 trial found serious hypoglycaemia nearly doubled. FDA had first issued a complete response letter in July 2024, citing manufacturing and the type 1 diabetes indication.", "mechanism": "Once-weekly insulin receptor agonism via three mechanisms: (1) the A14, B16, B25 substitutions reduce insulin receptor binding affinity, which paradoxically extends half-life by slowing receptor-mediated clearance; (2) the C20 fatty diacid side chain produces extremely high reversible albumin binding (>99%), creating a large circulating reservoir; (3) the dose is administered as a pre-amplified weekly equivalent (~7× daily glargine), which steady-state-titrates to a stable weekly area-under-curve equivalent to daily dosing.", "primaryUses": [ "Glycaemic control in adults with type 2 diabetes (US label)" ], "typicalDose": { "range": null, "unit": "units", "frequency": "once weekly", "route": "subcutaneous", "notes": "T2DM starting dose typically 70 units weekly; titrated weekly to fasting glucose target. T1DM initiation requires careful protocol given hypoglycemia risk." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Awiqli (insulin icodec-abae) injection Prescribing Information, sections 1 and 2 (DailyMed version 1, effective March 26, 2026; read September 30, 2026)." }, { "type": "pubmed", "citation": "Rosenstock J, et al. \"Weekly Icodec versus Daily Glargine U100 in Type 2 Diabetes without Previous Insulin.\" N Engl J Med, 2023;389(4):297-308. PMID: 37356066.", "pmid": "37356066" }, { "type": "pubmed", "citation": "Lingvay I, et al. \"Once-Weekly Insulin Icodec vs Once-Daily Insulin Degludec in Adults With Insulin-Naive Type 2 Diabetes: The ONWARDS 3 Randomized Clinical Trial.\" JAMA, 2023;330(3):228-237. PMID: 37354562.", "pmid": "37354562" }, { "type": "pubmed", "citation": "Philis-Tsimikas A, et al. \"Switching to once-weekly insulin icodec versus once-daily insulin degludec in individuals with basal insulin-treated type 2 diabetes (ONWARDS 2): a phase 3a, randomised, open label, multicentre, treat-to-target trial.\" Lancet Diabetes Endocrinol, 2023;11(6):414-425. PMID: 37148899.", "pmid": "37148899" }, { "type": "pubmed", "citation": "Russell-Jones D, et al. \"Once-weekly insulin icodec versus once-daily insulin degludec as part of a basal-bolus regimen in individuals with type 1 diabetes (ONWARDS 6): a phase 3a, randomised, open-label, treat-to-target trial.\" Lancet, 2023;402(10413):1636-1647. PMID: 37863084.", "pmid": "37863084" }, { "type": "other", "citation": "Novo Nordisk A/S, Form 6-K, July 10, 2024: FDA complete response letter for insulin icodec, citing manufacturing and the type 1 indication. Read September 30, 2026." }, { "type": "other", "citation": "US FDA, Drugs@FDA (openFDA): AWIQLI FLEXTOUCH, BLA 761326, original approval March 26, 2026. Read September 30, 2026." } ], "interactionCoverage": "label", "related": [ "insulin-glargine", "insulin-degludec", "insulin-efsitora" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": "EU (EMA), UK, Canada, Switzerland, Japan", "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S4.4.2", "named": false, "wording": "Insulins and insulin-mimetics", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Insulins are prohibited as a class; athletes with diabetes use them under a Therapeutic Use Exemption." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S4.4.2", "named": false, "wording": "Insulins and insulin-mimetics", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Insulins are prohibited as a class; athletes with diabetes use them under a Therapeutic Use Exemption." } ], "moleculeClass": "protein", "moleculeClassBasis": "insulin analog" }, { "id": "insulin-lispro", "name": "Insulin lispro", "aliases": [ "Humalog", "Admelog", "Lyumjev", "LY275585" ], "tier": "mid", "category": "metabolic", "subcategory": "rapid-acting insulin analog", "class": "A rapid-acting recombinant human insulin analog in which proline at B28 and lysine at B29 are swapped (hence \"lispro\" — Lys-B28, Pro-B29).", "tagline": "The first FDA-approved rapid-acting insulin analog (Humalog, Lilly, 1996) — the B28–B29 position swap prevents hexamer self-association, producing faster subcutaneous absorption than regular human insulin.", "oneLiner": "The first FDA-approved rapid-acting insulin analog (Humalog, Eli Lilly, approved 1996), created by swapping the positions of proline (B28) and lysine (B29) on the insulin B-chain to destabilize hexamer formation and accelerate subcutaneous absorption; Lyumjev (2020) is the same molecule with treprostinil and citrate excipients for ultra-rapid kinetics, and Admelog (Sanofi, 2017) is a follow-on biologic.", "sequence": "Modified human insulin with Lys(B28) / Pro(B29) swap", "molecularFormula": "C257H383N65O77S6", "molecularWeight": 5808, "halfLife": { "value": null, "unit": null, "range": "not reported in the sources read", "source": { "type": "none", "note": "searched PubMed on October 1, 2026; no human half-life figure in the sources read" } }, "fdaStatus": "approved", "approvalDetails": "The first insulin analogue approved, in 1996. The current Humalog application is BLA 205747 (May 26, 2015) and the ultra-rapid version Lyumjev is BLA 761109 (June 15, 2020); biosimilars are also marketed (Drugs@FDA, read October 1, 2026).", "mechanism": "Insulin receptor agonism — drives glucose uptake into muscle and adipose tissue, suppresses hepatic gluconeogenesis, and promotes glycogen and lipid synthesis. The B28–B29 swap prevents the zinc-coordinated hexamer self-association that delays absorption of regular human insulin, accelerating onset.", "primaryUses": [ "Type 1 diabetes mellitus (mealtime bolus)", "Type 2 diabetes mellitus requiring prandial insulin", "Insulin pump therapy (CSII)", "Diabetic ketoacidosis (adjunct)" ], "typicalDose": { "range": null, "unit": null, "frequency": "with meals", "route": "subcutaneous", "notes": "Individualised mealtime insulin. The ultra-rapid formulation and the original differ in absorption and are not interchangeable without adjustment." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Rosenstock J, et al. \"Tirzepatide vs Insulin Lispro Added to Basal Insulin in Type 2 Diabetes: The SURPASS-6 Randomized Clinical Trial.\" JAMA, 2023;330(17):1631-1640. PMID: 37786396.", "pmid": "37786396" }, { "type": "pubmed", "citation": "Leohr J, et al. \"Ultra-rapid lispro shows faster pharmacokinetics and reduces postprandial glucose excursions versus Humalog® in patients with type 2 diabetes mellitus in a randomized, controlled crossover meal test early phase study.\" Diabetes Obes Metab, 2022;24(2):187-195. PMID: 34605142.", "pmid": "34605142" }, { "type": "pubmed", "citation": "Garg SK, et al. \"Long-term efficacy of humalog in subjects with Type 1 diabetes mellitus.\" Diabet Med, 1999;16(5):384-7. PMID: 10342337.", "pmid": "10342337" }, { "type": "pubmed", "citation": "Leohr J, et al. \"Pharmacokinetics and Glucodynamics of Ultra Rapid Lispro (URLi) versus Humalog(®) (Lispro) in Patients with Type 2 Diabetes Mellitus: A Phase I Randomised, Crossover Study.\" Clin Pharmacokinet, 2020;59(12):1601-1610. PMID: 32468448.", "pmid": "32468448" }, { "type": "pubmed", "citation": "Shiramoto M, et al. \"Similar Pharmacokinetics and Pharmacodynamics of Biosimilar SAR342434 Insulin Lispro and Japan-Approved Humalog Insulin Lispro in Healthy Japanese Subjects.\" Clin Pharmacol Drug Dev, 2022;11(6):754-760. PMID: 35166054.", "pmid": "35166054" }, { "type": "pubmed", "citation": "Howey DC, et al. \"[Lys(B28), Pro(B29)]-human insulin. A rapidly absorbed analogue of human insulin.\" Diabetes, 1994;43(3):396-402. PMID: 8314011.", "pmid": "8314011" }, { "type": "fda-pi", "citation": "FDA. Humalog (insulin lispro) prescribing information. Eli Lilly, updated 2024." }, { "type": "fda-pi", "citation": "FDA. Lyumjev (insulin lispro-aabc) prescribing information. Eli Lilly, 2020." } ], "interactionCoverage": "label", "related": [ "insulin-aspart", "insulin-glulisine", "insulin-regular", "semaglutide" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S4.4.2", "named": false, "wording": "Insulins and insulin-mimetics", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Insulins are prohibited as a class; athletes with diabetes use them under a Therapeutic Use Exemption." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S4.4.2", "named": false, "wording": "Insulins and insulin-mimetics", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Insulins are prohibited as a class; athletes with diabetes use them under a Therapeutic Use Exemption." } ], "moleculeClass": "protein", "moleculeClassBasis": "insulin analog" }, { "id": "insulin-nph", "name": "NPH insulin (isophane)", "aliases": [ "Humulin N", "Novolin N", "isophane insulin", "NPH" ], "tier": "mid", "category": "metabolic", "subcategory": "intermediate-acting insulin", "class": "A protamine-crystallized suspension of recombinant human insulin (Neutral Protamine Hagedorn formulation).", "tagline": "The classical intermediate-acting insulin — regular human insulin co-crystallized with protamine to produce ~12-hour action; still widely used for cost reasons despite being largely superseded by analog basal insulins for T1DM.", "oneLiner": "Regular human insulin suspended as a protamine-complexed crystalline formulation (Neutral Protamine Hagedorn — named after its Danish inventor Hans Christian Hagedorn), producing slow dissolution from the SC depot and a ~12-hour duration profile; widely used before the analog era, now mostly relegated to budget-constrained settings and some twice-daily T2DM regimens given its sharp peak and higher hypoglycemia risk vs glargine/degludec.", "sequence": "Native human insulin complexed with protamine (1:1 molar ratio) + zinc", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": null, "range": "not reported in the sources read", "source": { "type": "none", "note": "searched PubMed on October 1, 2026; no human half-life figure in the sources read" } }, "fdaStatus": "approved", "approvalDetails": "Human NPH (isophane) insulin has been marketed for decades and is available from more than one manufacturer. Prescription status varies by US state.", "mechanism": "Insulin receptor agonism. Slow dissolution of the protamine-insulin complex from the SC depot produces the intermediate-acting profile. The peak is pronounced (roughly 4–12 hours post-injection), which drives higher nocturnal hypoglycemia risk than modern peakless analogs.", "primaryUses": [ "Type 1 diabetes mellitus (basal, twice-daily)", "Type 2 diabetes mellitus (basal)", "Gestational diabetes (preferred in some pregnancy regimens)" ], "typicalDose": { "range": null, "unit": null, "frequency": "once or twice daily", "route": "subcutaneous", "notes": "Individualised. Timing changes which part of the day is covered: bedtime dosing gave lower morning glucose, morning dosing lower evening glucose. The suspension must be resuspended before each injection." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Groop LC, et al. \"Morning or bedtime NPH insulin combined with sulfonylurea in treatment of NIDDM.\" Diabetes Care, 1992;15(7):831-4. PMID: 1516500.", "pmid": "1516500" }, { "type": "pubmed", "citation": "Semlitsch T, et al. \"(Ultra-)long-acting insulin analogues versus NPH insulin (human isophane insulin) for adults with type 2 diabetes mellitus.\" Cochrane Database Syst Rev, 2020;11(11):CD005613. PMID: 33166419.", "pmid": "33166419" }, { "type": "pubmed", "citation": "Thow JC, et al. \"Exercise augments the absorption of isophane (NPH) insulin.\" Diabet Med, 1989;6(4):342-5. PMID: 2524341.", "pmid": "2524341" }, { "type": "pubmed", "citation": "Thow JC, et al. \"Morphology of palpably abnormal injection sites and effects on absorption of isophane(NPH) insulin.\" Diabet Med, 1990;7(9):795-9. PMID: 2148131.", "pmid": "2148131" }, { "type": "pubmed", "citation": "Hendriksen KV, et al. \"Effects of insulin detemir and NPH insulin on renal handling of sodium, fluid retention and weight in type 2 diabetic patients.\" Diabetologia, 2012;55(1):46-50. PMID: 22002075.", "pmid": "22002075" }, { "type": "pubmed", "citation": "Hagedorn HC. \"Protamine Insulinate: (Section of Therapeutics and Pharmacology).\" Proc R Soc Med, 1937;30(6):805-14. PMID: 19991109.", "pmid": "19991109" }, { "type": "fda-pi", "citation": "FDA. Humulin N (NPH insulin) prescribing information. Eli Lilly." } ], "interactionCoverage": "label", "related": [ "insulin-regular", "insulin-glargine", "insulin-detemir", "insulin-degludec" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S4.4.2", "named": false, "wording": "Insulins and insulin-mimetics", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Insulins are prohibited as a class; athletes with diabetes use them under a Therapeutic Use Exemption." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S4.4.2", "named": false, "wording": "Insulins and insulin-mimetics", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Insulins are prohibited as a class; athletes with diabetes use them under a Therapeutic Use Exemption." } ], "moleculeClass": "protein", "moleculeClassBasis": "recombinant human insulin" }, { "id": "insulin-regular", "name": "Regular human insulin", "aliases": [ "Humulin R", "Novolin R", "Myxredlin", "Humulin R U-500" ], "tier": "mid", "category": "metabolic", "subcategory": "short-acting insulin", "class": "Recombinant human insulin with the native sequence (no modifications).", "tagline": "The original recombinant human insulin (Humulin R, 1982) — unmodified native sequence, short-acting kinetics driven by hexamer self-association; U-500 concentration for severely insulin-resistant patients.", "oneLiner": "Unmodified recombinant human insulin (Humulin R, Lilly, 1982; Novolin R, Novo Nordisk; Myxredlin, Baxter) — the first recombinant protein drug and the reference short-acting insulin against which all rapid-acting analogs are compared; available in standard U-100 concentration and a U-500 concentration (Humulin R U-500, 500 units/mL) for patients requiring >200 units/day.", "sequence": "Native human insulin (A-chain 21 aa + B-chain 30 aa, 3 disulfide bonds)", "molecularFormula": "C257H383N65O77S6", "molecularWeight": 5808, "halfLife": { "value": 1.5, "unit": "hours", "range": "about 1.5 hours after subcutaneous injection (range 40 minutes to 7 hours)", "notes": "Humulin R label, section 12.3; about 3.6 hours at higher doses in obese subjects.", "source": { "type": "label", "ref": "Humulin R prescribing information, section 12.3 (DailyMed version 35, effective June 16, 2026; read September 30, 2026)" } }, "fdaStatus": "approved", "approvalDetails": "FDA: HUMULIN R (insulin human injection), BLA 018780 (Eli Lilly), approved October 28, 1982 (Drugs@FDA), to improve glycemic control in adults and children with diabetes; label effective June 16, 2026. Novolin R (Novo Nordisk) and Myxredlin (premixed for intravenous use) are other regular human insulins.", "mechanism": "Insulin receptor agonism. The unmodified insulin self-associates into zinc-coordinated hexamers in the vial, and the rate-limiting step after SC injection is hexamer dissociation into absorption-competent monomers — which is why onset is slower and peak is later than rapid-acting analogs.", "primaryUses": [ "Type 1 diabetes mellitus (mealtime and IV use)", "Type 2 diabetes mellitus", "Diabetic ketoacidosis (IV)", "Hyperkalemia (IV, with dextrose)", "Severe insulin resistance (U-500)" ], "typicalDose": { "range": null, "unit": "units", "frequency": "3x daily before meals (SC) or continuous IV", "route": "subcutaneous or IV", "notes": "Fully individualized. IV use for DKA, hyperkalemia, or hospital glucose management." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Eli Lilly. HUMULIN R (insulin human injection), US prescribing information: indication, subcutaneous and intravenous administration, pharmacokinetics (apparent half-life about 1.5 hours subcutaneously; about 20 minutes to 1 hour intravenously). DailyMed version effective June 16, 2026; read September 30, 2026." }, { "type": "pubmed", "citation": "Hood RC, et al. \"TWO TREATMENT APPROACHES FOR HUMAN REGULAR U-500 INSULIN IN PATIENTS WITH TYPE 2 DIABETES NOT ACHIEVING ADEQUATE GLYCEMIC CONTROL ON HIGH-DOSE U-100 INSULIN THERAPY WITH OR WITHOUT ORAL AGENTS: A RANDOMIZED, TITRATION-TO-TARGET CLINICAL TRIAL.\" Endocr Pract, 2015;21(7):782-93. PMID: 25813411.", "pmid": "25813411" }, { "type": "pubmed", "citation": "Umpierrez GE, et al. \"Efficacy of subcutaneous insulin lispro versus continuous intravenous regular insulin for the treatment of patients with diabetic ketoacidosis.\" Am J Med, 2004;117(5):291-6. PMID: 15336577.", "pmid": "15336577" }, { "type": "pubmed", "citation": "Razavi Z, et al. \"Comparison of subcutaneous insulin aspart and intravenous regular insulin for the treatment of mild and moderate diabetic ketoacidosis in pediatric patients.\" Endocrine, 2018;61(2):267-274. PMID: 29797212.", "pmid": "29797212" }, { "type": "pubmed", "citation": "Murphy NP, et al. \"Randomized cross-over trial of insulin glargine plus lispro or NPH insulin plus regular human insulin in adolescents with type 1 diabetes on intensive insulin regimens.\" Diabetes Care, 2003;26(3):799-804. PMID: 12610040.", "pmid": "12610040" }, { "type": "pubmed", "citation": "Chen YC, et al. \"Intravenous regular insulin is an efficient and safe procedure for obtaining high-quality cardiac (18)F-FDG PET images: an open-label, single-center, randomized controlled prospective trial.\" J Nucl Cardiol, 2022;29(1):239-247. PMID: 32533427.", "pmid": "32533427" }, { "type": "fda", "citation": "FDA. Drugs@FDA (openFDA): HUMULIN R, BLA 018780, approved October 28, 1982. Read September 30, 2026." } ], "interactionCoverage": "label", "related": [ "insulin-nph", "insulin-lispro", "insulin-aspart" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S4.4.2", "named": false, "wording": "Insulins and insulin-mimetics", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Insulins are prohibited as a class; athletes with diabetes use them under a Therapeutic Use Exemption." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S4.4.2", "named": false, "wording": "Insulins and insulin-mimetics", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Insulins are prohibited as a class; athletes with diabetes use them under a Therapeutic Use Exemption." } ], "moleculeClass": "protein", "moleculeClassBasis": "Recombinant human insulin" }, { "id": "ipamorelin", "name": "Ipamorelin", "aliases": [ "NNC 26-0161", "Ipamorelin acetate" ], "tier": "full", "category": "growth-hormone", "subcategory": "selective GHRP / ghrelin receptor agonist", "class": "Synthetic pentapeptide growth hormone secretagogue (ghrelin-receptor agonist), selective for growth hormone over ACTH and cortisol in pigs.", "tagline": "A ghrelin-receptor agonist that released growth hormone without raising cortisol in pigs; in people it has one dosing study and a phase 2 surgery trial that found no benefit. Never approved.", "oneLiner": "A pentapeptide (Aib-His-D-2-Nal-D-Phe-Lys-NH2) from Novo Nordisk's 1990s growth hormone programme, code NNC 26-0161, that released growth hormone without raising ACTH or cortisol in pigs; its human record is one dosing study and a negative phase 2 trial.", "sequence": "Aib-His-D-2-Nal-D-Phe-Lys-NH2", "molecularFormula": "C38H49N9O5", "molecularWeight": 711.85, "halfLife": { "value": 2, "unit": "hours", "range": "~2 hours", "notes": "Terminal half-life after a 15-minute intravenous infusion in healthy men (1999); each dose produced one growth hormone pulse peaking at about 40 minutes." }, "fdaStatus": "discontinued", "approvalDetails": "Never approved. A 2014 phase 2 trial of intravenous ipamorelin after bowel surgery found no significant benefit over placebo. FDA placed ipamorelin acetate in 503B Category 2 on September 29, 2023; its 503A nomination was withdrawn.", "mechanism": "Agonist at the ghrelin (GHRP) receptor that releases growth hormone with a potency close to GHRP-6's in rat pituitary cells and animals. In pigs it did not raise ACTH or cortisol even at more than 200 times its effective dose, unlike GHRP-6 and GHRP-2; that selectivity has not been measured in a published human study. As a ghrelin mimetic it speeds gut transit in rodents.", "primaryUses": [ "GH-axis research (animal studies)", "Postoperative ileus (phase 2 trial, 2014; no significant benefit)", "Community GH-axis protocols (untested in humans)" ], "typicalDose": { "range": "100–300", "unit": "mcg", "frequency": "1–3 times daily", "route": "subcutaneous", "notes": "Community figures only. The human studies gave it intravenously: single infusions of about 3 to 100 µg/kg (1999) and 0.03 mg/kg twice daily after surgery (2014)." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "Gobburu JV, et al. \"Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers.\" Pharm Res, 1999;16(9):1412-6. PMID: 10496658.", "pmid": "10496658" }, { "type": "clinical-trial", "citation": "Beck DE, et al. \"Prospective, randomized, controlled, proof-of-concept study of the Ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients.\" Int J Colorectal Dis, 2014;29(12):1527-34. PMID: 25331030.", "pmid": "25331030" }, { "type": "pubmed", "citation": "Semenistaya E, et al. \"Determination of growth hormone releasing peptides metabolites in human urine after nasal administration of GHRP-1, GHRP-2, GHRP-6, Hexarelin, and Ipamorelin.\" Drug Test Anal, 2015;7(10):919-25. PMID: 25869809.", "pmid": "25869809" }, { "type": "pubmed", "citation": "Raun K, et al. \"Ipamorelin, the first selective growth hormone secretagogue.\" Eur J Endocrinol, 1998;139(5):552-61. PMID: 9849822.", "pmid": "9849822" }, { "type": "pubmed", "citation": "Johansen PB, et al. \"Pharmacokinetic evaluation of ipamorelin and other peptidyl growth hormone secretagogues with emphasis on nasal absorption.\" Xenobiotica, 1998;28(11):1083-92. PMID: 9879640.", "pmid": "9879640" }, { "type": "pubmed", "citation": "Johansen PB, et al. \"Ipamorelin, a new growth-hormone-releasing peptide, induces longitudinal bone growth in rats.\" Growth Horm IGF Res, 1999;9(2):106-13. PMID: 10373343.", "pmid": "10373343" }, { "type": "pubmed", "citation": "Svensson J, et al. \"The GH secretagogues ipamorelin and GH-releasing peptide-6 increase bone mineral content in adult female rats.\" J Endocrinol, 2000;165(3):569-77. PMID: 10828840.", "pmid": "10828840" }, { "type": "pubmed", "citation": "Andersen NB, et al. \"The growth hormone secretagogue ipamorelin counteracts glucocorticoid-induced decrease in bone formation of adult rats.\" Growth Horm IGF Res, 2001;11(5):266-72. PMID: 11735244.", "pmid": "11735244" }, { "type": "pubmed", "citation": "Jiménez-Reina L, et al. \"Influence of chronic treatment with the growth hormone secretagogue Ipamorelin, in young female rats: somatotroph response in vitro.\" Histol Histopathol, 2002;17(3):707-14. PMID: 12168778.", "pmid": "12168778" }, { "type": "pubmed", "citation": "Venkova K, et al. \"Efficacy of ipamorelin, a novel ghrelin mimetic, in a rodent model of postoperative ileus.\" J Pharmacol Exp Ther, 2009;329(3):1110-6. PMID: 19289567.", "pmid": "19289567" }, { "type": "pubmed", "citation": "Greenwood-Van Meerveld B, et al. \"Efficacy of ipamorelin, a ghrelin mimetic, on gastric dysmotility in a rodent model of postoperative ileus.\" J Exp Pharmacol, 2012;4:149-55. PMID: 27186127.", "pmid": "27186127" }, { "type": "pubmed", "citation": "Lu Z, et al. \"The growth hormone secretagogue receptor 1a agonists, anamorelin and ipamorelin, inhibit cisplatin-induced weight loss in ferrets: Anamorelin also exhibits anti-emetic effects via a central mechanism.\" Physiol Behav, 2024;284:114644. PMID: 39043357.", "pmid": "39043357" }, { "type": "pubmed", "citation": "Gouda M, et al. \"The influence of ghrelin agonist ipamorelin acetate on the hypothalamic-pituitary-testicular axis in a cichlid fish, Oreochromis mossambicus.\" Anim Reprod Sci, 2024;268:107550. PMID: 38996787.", "pmid": "38996787" }, { "type": "pubmed", "citation": "Adeghate E, et al. \"Mechanism of ipamorelin-evoked insulin release from the pancreas of normal and diabetic rats.\" Neuro Endocrinol Lett, 2004;25(6):403-6. PMID: 15665799.", "pmid": "15665799" }, { "type": "other", "citation": "U.S. Food and Drug Administration. Certain bulk drug substances for use in compounding that may present significant safety risks (ipamorelin acetate, 503B category 2 since September 29, 2023). Content current as of April 22, 2026; read September 26, 2026." } ], "interactionCoverage": "partial", "related": [ "cjc-1295", "mod-grf-1-29", "ghrp-2", "ghrp-6", "sermorelin" ], "lastReviewed": "2026-09-26", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.2.4", "named": true, "wording": "ipamorelin", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.2.4", "named": true, "wording": "ipamorelin", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "kisspeptin-10", "name": "Kisspeptin-10", "aliases": [ "Kp-10", "metastin 45-54", "KISS1(68-77)" ], "tier": "mid", "category": "sexual-health", "subcategory": "GnRH/reproductive-axis regulator", "class": "The C-terminal 10-amino-acid fragment of kisspeptin — the master regulator of the reproductive axis acting via the KISS1R (GPR54) receptor.", "tagline": "A short active fragment of human kisspeptin — under active clinical investigation for hypothalamic amenorrhea, infertility, and low libido in men and women.", "oneLiner": "The bioactive C-terminal decapeptide of the kisspeptin family, acting at KISS1R on hypothalamic GnRH neurons to restore pulsatile GnRH release — with extensive Phase 1/2 human data from the Dhillo group (Imperial College London).", "sequence": "YNWNSFGLRF-NH2", "molecularFormula": "C63H83N17O14", "molecularWeight": 1302.4, "halfLife": { "value": null, "unit": "minutes", "range": "short; not established in the studies cited", "notes": "The dataset's earlier figure of about 4 minutes had no source on this page and was removed. Formula and weight are PubChem's (CID 25240297).", "source": { "type": "qualitative", "note": "a description with no figure; no half-life measurement is cited for it" } }, "fdaStatus": "clinical-trials", "approvalDetails": "Not approved. Multiple Phase 1 and Phase 2 human trials completed in hypothalamic amenorrhea, idiopathic hypogonadotropic hypogonadism, IVF triggering (typically using kisspeptin-54), and sexual desire disorders. Ongoing trials registered on ClinicalTrials.gov.", "mechanism": "Full agonist at KISS1R (GPR54) on hypothalamic GnRH neurons, mobilizing intracellular calcium via Gq/11α signaling and activating ERK1/2 and p38 MAPK cascades. Downstream effect is pulsatile release of GnRH, which drives LH and FSH secretion and restores endogenous gonadal steroid production. Used pulsatile, kisspeptin can reactivate a quiescent reproductive axis without causing receptor desensitization.", "primaryUses": [ "Hypothalamic amenorrhea (clinical trials)", "Idiopathic hypogonadotropic hypogonadism", "Male hypogonadism research", "Sexual desire disorder research", "IVF triggering (kisspeptin-54, not kisspeptin-10)" ], "typicalDose": { "range": "varies", "unit": "", "frequency": "pulsatile (Q10min to hourly)", "route": "subcutaneous or intravenous", "notes": "Clinical trial doses have ranged from 0.24 nmol/kg/IV bolus to continuous subcutaneous pulsatile infusion. Community injectable use protocols have no clinical backing." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "George JT, et al. \"Kisspeptin-10 is a potent stimulator of LH and increases pulse frequency in men.\" J Clin Endocrinol Metab, 2011;96(8):E1228-36. PMID: 21632807.", "pmid": "21632807" }, { "type": "pubmed", "citation": "Jayasena CN, et al. \"The effects of kisspeptin-10 on reproductive hormone release show sexual dimorphism in humans.\" J Clin Endocrinol Metab, 2011;96(12):E1963-72. PMID: 21976724.", "pmid": "21976724" }, { "type": "pubmed", "citation": "George JT, et al. \"Exploring the pathophysiology of hypogonadism in men with type 2 diabetes: kisspeptin-10 stimulates serum testosterone and LH secretion in men with type 2 diabetes and mild biochemical hypogonadism.\" Clin Endocrinol (Oxf), 2013;79(1):100-4. PMID: 23153270.", "pmid": "23153270" }, { "type": "pubmed", "citation": "Millar RP, et al. \"Hypothalamic-Pituitary-Ovarian Axis Reactivation by Kisspeptin-10 in Hyperprolactinemic Women With Chronic Amenorrhea.\" J Endocr Soc, 2017;1(11):1362-1371. PMID: 29264460.", "pmid": "29264460" }, { "type": "fda", "citation": "FDA. Bulk Drug Substances Nominated for Use in Compounding Under Section 503A: Category 2 includes kisspeptin-10 (updated May 14, 2026). Read September 30, 2026." } ], "interactionCoverage": "studied", "related": [ "kisspeptin-54", "hcg", "pt-141" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.2.1", "named": true, "wording": "kisspeptin and its agonist analogues", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "malesOnly": true }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.2.1", "named": true, "wording": "kisspeptin and its agonist analogues", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "malesOnly": true } ], "moleculeClass": "peptide" }, { "id": "kisspeptin-54", "name": "Kisspeptin-54", "aliases": [ "Kp-54", "metastin", "KISS1(68-121)" ], "tier": "mid", "category": "sexual-health", "subcategory": "reproductive axis regulator", "class": "The full-length mature kisspeptin peptide — 54 amino acids, the endogenous ligand for KISS1R.", "tagline": "The full-length 54-amino-acid kisspeptin, the peptide that drives GnRH release. Its furthest-developed use is a single injection to trigger egg maturation in IVF: eggs matured in 95% of 60 women at high risk of ovarian hyperstimulation syndrome, with no moderate or worse case. Investigational, and prohibited in sport.", "oneLiner": "The full-length mature kisspeptin, 54 amino acids, the endogenous KISS1R ligand. Trialled as a single subcutaneous trigger of egg maturation in IVF at 1.6 to 12.8 nmol/kg, as a 6.4 nmol/kg bolus to test hypothalamic GnRH function, and as an infusion; not approved anywhere.", "sequence": "GTSLSPPPESSGSPQQPGLSAPHSRQIPAPQGAVLVQREKDLPNYNWNSFGLRF-NH2", "molecularFormula": null, "molecularWeight": 5858.39, "halfLife": { "value": 27.6, "unit": "minutes", "range": "about 28 minutes (plasma)", "source": { "type": "pmid", "pmid": "16174713", "cite": "Dhillo WS, et al. \"Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males.\" J Clin Endocrinol Metab, 2005;90(12):6609-15. PMID: 16174713." } }, "fdaStatus": "clinical-trials", "approvalDetails": "Not approved anywhere; Drugs@FDA holds no application for kisspeptin (openFDA, read September 30, 2026).", "mechanism": "Full agonist at KISS1R (GPR54) on GnRH neurons in the hypothalamus. Activates Gq/11α → PLCβ → IP3/DAG → intracellular Ca²⁺ mobilization, depolarizing GnRH neurons and triggering LH and FSH pulses. As an IVF trigger, produces an endogenous LH surge that induces final oocyte maturation without the sustained receptor activation of hCG, which is the mechanistic basis for its reduced OHSS risk.", "primaryUses": [ "Trigger for egg maturation in IVF (phase 2)", "Test of hypothalamic GnRH neuronal function (research)", "Reproductive hormone physiology (research)" ], "typicalDose": { "range": "1.6–12.8", "unit": "nmol/kg", "frequency": "single injection (IVF trigger)", "route": "subcutaneous", "notes": "The IVF trials' range; a 6.4 nmol/kg bolus is used as a hypothalamic test." }, "evidenceLevel": "medium", "sources": [ { "type": "fda", "citation": "FDA. Drugs@FDA (openFDA): no application for kisspeptin. Read September 30, 2026." }, { "type": "pubmed", "citation": "Abbara A, et al. \"Efficacy of Kisspeptin-54 to Trigger Oocyte Maturation in Women at High Risk of Ovarian Hyperstimulation Syndrome (OHSS) During In Vitro Fertilization (IVF) Therapy.\" J Clin Endocrinol Metab, 2015;100(9):3322-31. PMID: 26192876.", "pmid": "26192876" }, { "type": "pubmed", "citation": "Jayasena CN, et al. \"Kisspeptin-54 triggers egg maturation in women undergoing in vitro fertilization.\" J Clin Invest, 2014;124(8):3667-77. PMID: 25036713.", "pmid": "25036713" }, { "type": "pubmed", "citation": "Abbara A, et al. \"Kisspeptin-54 Accurately Identifies Hypothalamic Gonadotropin-Releasing Hormone Neuronal Dysfunction in Men with Congenital Hypogonadotropic Hypogonadism.\" Neuroendocrinology, 2021;111(12):1176-1186. PMID: 33227799.", "pmid": "33227799" }, { "type": "pubmed", "citation": "Jayasena CN, et al. \"Twice-daily subcutaneous injection of kisspeptin-54 does not abolish menstrual cyclicity in healthy female volunteers.\" J Clin Endocrinol Metab, 2013;98(11):4464-74. PMID: 24030945.", "pmid": "24030945" }, { "type": "pubmed", "citation": "Owens LA, et al. \"The direct and indirect effects of kisspeptin-54 on granulosa lutein cell function.\" Hum Reprod, 2018;33(2):292-302. PMID: 29206944.", "pmid": "29206944" }, { "type": "pubmed", "citation": "Dhillo WS, et al. \"Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males.\" J Clin Endocrinol Metab, 2005;90(12):6609-15. PMID: 16174713.", "pmid": "16174713" } ], "interactionCoverage": "studied", "related": [ "kisspeptin-10", "hcg" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.2.1", "named": true, "wording": "kisspeptin and its agonist analogues", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "malesOnly": true }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.2.1", "named": true, "wording": "kisspeptin and its agonist analogues", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "malesOnly": true } ], "moleculeClass": "peptide" }, { "id": "klotho-peptide", "name": "Klotho Peptide", "aliases": [ "KL-VS", "Soluble Klotho", "α-Klotho", "S-Klotho" ], "tier": "mid", "category": "longevity", "subcategory": "longevity-associated protein/peptide", "class": "A soluble fragment of the transmembrane protein α-Klotho, named after the Greek Fate who spins the thread of life, associated with lifespan extension and cognitive enhancement in animal and human studies.", "tagline": "The kidney protein whose shed form circulates in blood and works with FGF23 on mineral balance, sold online as a longevity peptide. No published trial has given klotho to a person: human studies measure it, and 24 weeks of supervised exercise in 144 young adults did not move it. Research only.", "oneLiner": "Alpha-klotho, a protein made mainly by the kidney whose soluble form acts as a circulating co-receptor for FGF23. Studied in people only as a measured biomarker of kidney, vascular and metabolic health; no trial has administered klotho, and no human dose exists.", "sequence": "Soluble ectodomain of α-Klotho protein (~130 kDa); not a small peptide per se", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": null, "range": "Not established in people", "notes": "Klotho has not been given to people in a published trial, so no human pharmacokinetics exist.", "source": { "type": "qualitative", "note": "a description with no figure; no half-life measurement is cited for it" } }, "fdaStatus": "research-only", "approvalDetails": "Not approved anywhere; Drugs@FDA holds no application for klotho (openFDA, read September 30, 2026).", "mechanism": "Multiple mechanisms: (1) Inhibits insulin/IGF-1 signaling, activating FOXO transcription factors and promoting stress resistance; (2) Suppresses Wnt signaling, reducing cellular senescence and fibrosis; (3) Enhances synaptic plasticity by increasing GluN2B-containing NMDA receptor trafficking to the synapse; (4) Regulates FGF23-mediated phosphate metabolism in kidney; (5) Reduces oxidative stress via Nrf2 activation.", "primaryUses": [ "Biomarker of kidney and vascular health (research)", "Ageing and mineral-metabolism research" ], "typicalDose": { "range": "Not established", "unit": null, "frequency": null, "route": null, "notes": "No published trial has given klotho to a person." }, "evidenceLevel": "medium", "sources": [ { "type": "fda", "citation": "FDA. Drugs@FDA (openFDA): no application for klotho. Read September 30, 2026." }, { "type": "pubmed", "citation": "Cheng YW, et al. \"Association between Soluble α-Klotho Protein and Metabolic Syndrome in the Adult Population.\" Biomolecules, 2022;12(1). PMID: 35053218.", "pmid": "35053218" }, { "type": "pubmed", "citation": "Amaro-Gahete FJ, et al. \"Impact of 24-week supervised concurrent exercise on S-Klotho and vitamin D levels: A randomized controlled trial.\" J Sports Sci, 2024;42(24):2562-2571. PMID: 39831661.", "pmid": "39831661" }, { "type": "pubmed", "citation": "Navarro-Lomas G, et al. \"Exercise-induced changes in plasma S-Klotho levels are associated with the obtained enhancements of heart rate variability in sedentary middle-aged adults: the FIT-AGEING study.\" J Physiol Biochem, 2024;80(2):317-328. PMID: 38175501.", "pmid": "38175501" }, { "type": "pubmed", "citation": "Edmonston D, et al. \"FGF23 and klotho at the intersection of kidney and cardiovascular disease.\" Nat Rev Cardiol, 2024;21(1):11-24. PMID: 37443358.", "pmid": "37443358" }, { "type": "pubmed", "citation": "Kurosu H, et al. \"Suppression of aging in mice by the hormone Klotho.\" Science, 2005;309(5742):1829-33. PMID: 16123266.", "pmid": "16123266" }, { "type": "pubmed", "citation": "Castner SA, et al. \"Longevity factor klotho enhances cognition in aged nonhuman primates.\" Nat Aging, 2023;3(8):931-937. PMID: 37400721.", "pmid": "37400721" } ], "interactionCoverage": "unreviewed", "related": [ "foxo4-dri", "epithalon", "humanin", "mots-c", "gdf11" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-20", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "protein", "moleculeClassBasis": "transmembrane protein" }, { "id": "kn056", "name": "KN056", "aliases": [ "KN-056" ], "tier": "stub", "category": "pipeline", "subcategory": "GLP-1 / glucagon dual agonist (early clinical)", "class": "A dual GLP-1 / glucagon receptor agonist peptide developed by Alphamab Oncology / Alphamab Biopharma (China).", "tagline": "Alphamab's GLP-1 / glucagon dual agonist — an early-clinical Chinese entry in the GLP-1/glucagon mechanism space pioneered by cotadutide and now represented by pemvidutide and survodutide.", "oneLiner": "A dual GLP-1 / glucagon receptor agonist peptide developed by Alphamab (Suzhou), in early clinical development in China for obesity and MASH; occupies the same mechanism space as pemvidutide, survodutide, and the discontinued cotadutide.", "sequence": null, "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": "days", "range": "long-acting design", "notes": "Engineered for weekly dosing." }, "fdaStatus": "clinical-trials", "approvalDetails": "Not approved. Early clinical development in China.", "mechanism": "Balanced agonism at GLP-1 and glucagon receptors — same mechanism class as cotadutide, pemvidutide, and survodutide. The glucagon arm adds thermogenesis / hepatic fat oxidation to standard GLP-1 incretin effects.", "primaryUses": [ "Obesity (early clinical)", "MASH (early clinical)" ], "typicalDose": { "range": null, "unit": null, "frequency": "once weekly", "route": "subcutaneous", "notes": "Early-clinical doses not publicly finalized." }, "evidenceLevel": "low", "sources": [ { "type": "manufacturer", "citation": "Alphamab pipeline disclosures — KN056 GLP-1/glucagon dual agonist." } ], "interactionCoverage": "none-found", "related": [ "cotadutide", "pemvidutide", "survodutide" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." } ], "moleculeClass": "peptide" }, { "id": "kpv", "name": "KPV", "aliases": [ "Lys-Pro-Val", "α-MSH(11-13)", "tripeptide KPV", "lysine-proline-valine" ], "tier": "full", "category": "healing", "subcategory": "anti-inflammatory tripeptide", "class": "The C-terminal tripeptide fragment of alpha-melanocyte-stimulating hormone (α-MSH), with broad anti-inflammatory properties.", "tagline": "A tripeptide from the tail of α-MSH: anti-inflammatory in mouse colitis and cell studies, never tested in people, and recommended for compounding by FDA's advisers in July 2026.", "oneLiner": "The last three amino acids of α-melanocyte-stimulating hormone (lysine-proline-valine), which enters cells through the PepT1 transporter and damps NF-κB signalling in laboratory and mouse studies.", "sequence": "Lys-Pro-Val", "molecularFormula": "C16H30N4O4", "molecularWeight": 342.44, "halfLife": { "value": null, "unit": null, "range": "not measured", "notes": "No pharmacokinetic study in any species is in our evidence set. Under acid, alkali and oxidising stress it degrades mainly to lysyl-proline diketopiperazine (2015 HPLC study)." }, "fdaStatus": "research-only", "approvalDetails": "Never approved anywhere, and no published study has given it to people. In 503A Category 2 until its nomination was withdrawn in April 2026; FDA's advisory committee voted 8–6 (one abstention) on July 23, 2026 to recommend it for the 503A list, against FDA staff's proposal. FDA had not acted as of September 27, 2026.", "mechanism": "Enters gut epithelial and immune cells through the di/tripeptide transporter PepT1, which inflammation induces in the colon, and suppresses NF-κB and MAP kinase signalling; in airway cells it enters the nucleus and appears to block NF-κB p65's importin binding site. Its anti-inflammatory effect persisted in mice without functional MC1R, was not blocked by an MC3/4 antagonist and did not raise cAMP. All evidence is from cells and rodents.", "primaryUses": [ "Inflammatory bowel disease research", "Psoriasis and acne research", "Candidate for gut barrier inflammation", "Community oral use for gut healing (combined with BPC-157)" ], "typicalDose": { "range": "200–500", "unit": "mcg", "frequency": "once daily", "route": "oral (community); preclinical via various routes", "notes": "Community oral dosing; no clinical standard." }, "evidenceLevel": "low", "sources": [ { "type": "Animal", "citation": "Richards DB, et al. \"Effect of alpha-MSH 11-13 (lysine-proline-valine) on fever in the rabbit.\" Peptides, 1984;5(4):815-7. PMID: 6333677.", "pmid": "6333677" }, { "type": "Animal", "citation": "Getting SJ, et al. \"Dissection of the anti-inflammatory effect of the core and C-terminal (KPV) alpha-melanocyte-stimulating hormone peptides.\" J Pharmacol Exp Ther, 2003;306(2):631-7. PMID: 12750433.", "pmid": "12750433" }, { "type": "In Vitro", "citation": "Elliott RJ, et al. \"alpha-Melanocyte-stimulating hormone, MSH 11-13 KPV and adrenocorticotropic hormone signalling in human keratinocyte cells.\" J Invest Dermatol, 2004;122(4):1010-9. PMID: 15102092.", "pmid": "15102092" }, { "type": "Animal", "citation": "Dalmasso G, et al. \"PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation.\" Gastroenterology, 2008;134(1):166-78. PMID: 18061177.", "pmid": "18061177" }, { "type": "Animal", "citation": "Kannengiesser K, et al. \"Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease.\" Inflamm Bowel Dis, 2008;14(3):324-31. PMID: 18092346.", "pmid": "18092346" }, { "type": "In Vitro", "citation": "Land SC. \"Inhibition of cellular and systemic inflammation cues in human bronchial epithelial cells by melanocortin-related peptides: mechanism of KPV action and a role for MC3R agonists.\" Int J Physiol Pathophysiol Pharmacol, 2012;4(2):59-73. PMID: 22837805.", "pmid": "22837805" }, { "type": "In Vitro", "citation": "Pawar KR, et al. \"Stability-indicating HPLC assay for lysine-proline-valine (KPV) in aqueous solutions and skin homogenates.\" Biomed Chromatogr, 2015;29(5):716-21. PMID: 25298219.", "pmid": "25298219" }, { "type": "Animal", "citation": "Viennois E, et al. \"Critical role of PepT1 in promoting colitis-associated cancer and therapeutic benefits of the anti-inflammatory PepT1-mediated tripeptide KPV in a murine model.\" Cell Mol Gastroenterol Hepatol, 2016;2(3):340-357. PMID: 27458604.", "pmid": "27458604" }, { "type": "Animal", "citation": "Xiao B, et al. \"Orally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis.\" Mol Ther, 2017;25(7):1628-1640. PMID: 28143741.", "pmid": "28143741" }, { "type": "In Vitro", "citation": "Pawar K, et al. \"Transdermal Iontophoretic Delivery of Lysine-Proline-Valine (KPV) Peptide Across Microporated Human Skin.\" J Pharm Sci, 2017;106(7):1814-1820. PMID: 28343991.", "pmid": "28343991" }, { "type": "Animal", "citation": "Sun J, et al. \"Self-Cross-Linked Hydrogel of Cysteamine-Grafted γ-Polyglutamic Acid Stabilized Tripeptide KPV for Alleviating TNBS-Induced Ulcerative Colitis in Rats.\" ACS Biomater Sci Eng, 2021;7(10):4859-4869. PMID: 34547895.", "pmid": "34547895" }, { "type": "Animal", "citation": "Zhao Y, et al. \"A KPV-binding double-network hydrogel restores gut mucosal barrier in an inflamed colon.\" Acta Biomater, 2022;143:233-252. PMID: 35245681.", "pmid": "35245681" }, { "type": "In Vitro", "citation": "Sung J, et al. \"Lysine-Proline-Valine peptide mitigates fine dust-induced keratinocyte apoptosis and inflammation by regulating oxidative stress and modulating the MAPK/NF-κB pathway.\" Tissue Cell, 2025;95:102837. PMID: 40073467.", "pmid": "40073467" }, { "type": "Animal", "citation": "An SH, et al. \"KPV attenuates adipogenesis and lipid metabolism through modulation of ROS-mediated AKT/mTORC1/PPARγ signaling.\" Tissue Cell, 2026;104(Pt 1):103837. PMID: 42585803.", "pmid": "42585803" } ], "interactionCoverage": "unreviewed", "related": [ "bpc-157", "larazotide", "ll-37" ], "lastReviewed": "2026-09-27", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "kr-12", "name": "KR-12", "aliases": [ "LL-37(18-29)", "KRIVQRIKDFLR", "minimal LL-37 antimicrobial fragment" ], "tier": "stub", "category": "healing", "subcategory": "LL-37-derived antimicrobial peptide fragment", "class": "A 12-amino-acid synthetic fragment of LL-37 spanning residues 18–29, characterized as the smallest LL-37 fragment that retains bactericidal activity against Gram-negative bacteria while showing minimal toxicity toward host cells.", "tagline": "KRIVQRIKDFLR — the minimal 12-residue bactericidal fragment of LL-37. Retains selective antimicrobial activity while losing LL-37's host-cell toxicity, making it the canonical template for LL-37-derived antimicrobial peptide drug discovery. Research-only.", "oneLiner": "A 12-residue peptide corresponding to LL-37 residues 18–29 (Lys-Arg-Ile-Val-Gln-Arg-Ile-Lys-Asp-Phe-Leu-Arg), characterized by Guangshun Wang's group at the University of Nebraska Medical Center as the smallest LL-37 fragment that retains bactericidal activity against Escherichia coli while showing minimal hemolytic and cytotoxic activity against human erythrocytes and keratinocytes. KR-12 has become the canonical minimal LL-37 template for antimicrobial peptide drug discovery, with multiple groups producing chemically modified, D-amino-acid-substituted, and lipidated analogs intended to overcome the proteolytic-instability limitation of the native L-amino-acid peptide. Not FDA-approved; not in clinical development as a standalone agent.", "sequence": "Lys-Arg-Ile-Val-Gln-Arg-Ile-Lys-Asp-Phe-Leu-Arg", "molecularFormula": "C70H124N22O16", "molecularWeight": 1570.91, "halfLife": { "value": null, "unit": null, "range": "Minutes (proteolytic degradation)", "notes": "Native L-amino-acid KR-12 is rapidly degraded by serum and tissue proteases; D-amino-acid and retro-inverso analogs have substantially extended plasma stability and are the primary route of clinical translation." }, "fdaStatus": "research-only", "approvalDetails": "Native KR-12 is not FDA-approved. Various KR-12 derivatives and analogs are in preclinical and early-clinical development for topical antimicrobial and wound-healing applications, but no KR-12-based agent has entered a registered Phase 2 or later clinical trial as of early 2026.", "mechanism": "Forms amphipathic α-helix on contact with negatively charged bacterial membrane lipids (particularly phosphatidylglycerol and cardiolipin), producing rapid membrane permeabilization through a carpet-or-toroidal-pore mechanism. The 12-residue size appears to be near the minimum for coherent amphipathic α-helix formation in a membrane environment. Selectivity for bacterial over mammalian membranes arises from the charge difference between bacterial (negatively charged) and mammalian (largely zwitterionic) outer-leaflet phospholipids. Also retains weak LPS-neutralizing activity of the parent LL-37.", "primaryUses": [ "Antimicrobial peptide research (in vitro and preclinical)", "Template for LL-37-derived antibiotic drug discovery", "Wound-healing biomaterial research (peptide-functionalized hydrogels and dressings)" ], "typicalDose": { "range": "Not established for human use", "unit": null, "frequency": null, "route": null, "notes": "⚠ No human dosing established. Topical preclinical studies have used μM-to-mM concentrations. Any human use would be unregulated." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "Wang G. \"Structures of human host defense cathelicidin LL-37 and its smallest antimicrobial peptide KR-12 in lipid micelles.\" J Biol Chem, 2008;283:32637-32643 (KR-12 minimal-fragment characterization). PMID: 18818205.", "pmid": "18818205" }, { "type": "pubmed", "citation": "Mishra B, Wang G. \"Ab initio design of potent anti-MRSA peptides based on database filtering technology.\" J Am Chem Soc, 2012;134:12426-12429. PMID: 22803960.", "pmid": "22803960" }, { "type": "review", "citation": "Wang G, Narayana JL, et al. \"Human antimicrobial peptides and proteins.\" Pharmaceuticals (Basel), 2014;7:545-594. PMID: 24828484.", "pmid": "24828484" } ], "interactionCoverage": "unreviewed", "related": [ "ll-37", "fk-13" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "lactoferricin", "name": "Lactoferricin", "aliases": [ "Lactoferricin B", "LfcinB", "Lactoferricin H" ], "tier": "stub", "category": "immune", "subcategory": "antimicrobial peptide", "class": "A cationic antimicrobial peptide released by pepsin digestion of lactoferrin, with broad-spectrum antimicrobial, anti-biofilm, and anticancer activity.", "tagline": "An antimicrobial peptide from mother's milk — a potent cationic fragment of lactoferrin with broad-spectrum activity against bacteria, fungi, viruses, and parasites, plus emerging anticancer properties.", "oneLiner": "A 25-amino-acid (bovine) or 47-amino-acid (human) cationic peptide liberated from the N-terminal domain of lactoferrin during gastric digestion, with antimicrobial activity exceeding that of the parent protein.", "sequence": "FKCRRWQWRMKKLGAPSITCVRRAF (bovine LfcinB, Cys-Cys disulfide loop)", "molecularFormula": "C141H222N46O30S4", "molecularWeight": 3124.8, "halfLife": { "value": null, "unit": null, "range": "Minutes in serum; active in gastrointestinal lumen", "notes": "Naturally generated in the infant gut during breastfeeding. Serum stability is limited but GI tract stability is sufficient for local antimicrobial action." }, "fdaStatus": "research-only", "approvalDetails": "Not approved as a therapeutic. Active area of research for antimicrobial peptide drug development and food safety applications.", "mechanism": "Binds bacterial LPS and lipoteichoic acid via electrostatic interactions between cationic residues and anionic membrane components. Inserts into microbial membranes causing permeabilization. Also inhibits biofilm formation, has direct antiviral activity (binds viral surface glycoproteins), and shows anticancer activity via mitochondrial membrane disruption in tumor cells while sparing normal cells.", "primaryUses": [ "Antimicrobial peptide research", "Anti-biofilm strategies", "Food preservation research", "Anticancer peptide development" ], "typicalDose": { "range": null, "unit": null, "frequency": null, "route": null, "notes": "Research reagent. No established therapeutic dosing." }, "evidenceLevel": "medium", "sources": [ { "type": "review", "citation": "Gifford JL, et al. \"Lactoferricin: a lactoferrin-derived peptide with antimicrobial, antiviral, antitumor and immunological properties.\" Cell Mol Life Sci, 2005;62:2588-2598. PMID: 16261252.", "pmid": "16261252" } ], "interactionCoverage": "unreviewed", "related": [ "ll-37", "pexiganan", "omiganan", "hnp-1" ], "lastReviewed": "2026-04-20", "publishedAt": "2026-04-20", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "langlenatide", "name": "Langlenatide", "aliases": [ "HM11260C (early)", "LAPS-Exendin-4" ], "tier": "stub", "category": "pipeline", "subcategory": "long-acting GLP-1 agonist (superseded)", "class": "An early long-acting exendin-4 construct from Hanmi Pharmaceutical based on the LAPSCOVERY platform.", "tagline": "Hanmi's original long-acting exendin-4 conjugate, superseded by efpeglenatide (the optimized successor) after early clinical work; effectively a program predecessor rather than an independent pipeline candidate.", "oneLiner": "An early Hanmi Pharmaceutical long-acting exendin-4 program, later iterated into efpeglenatide (HM11260C), the lead candidate that reached Phase 3; langlenatide as a distinct name appears mainly in historical pipeline documents.", "sequence": "Exendin-4 analog conjugated to Fc (LAPSCOVERY platform, early form)", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": null, "range": "undetermined", "notes": "Program data largely subsumed into efpeglenatide development record." }, "fdaStatus": "discontinued", "approvalDetails": "Not approved. Program subsumed into efpeglenatide (HM11260C) development; retained here for pipeline-history completeness.", "mechanism": "GLP-1 receptor agonism via long-acting exendin-4 conjugate. Mechanistically identical to efpeglenatide.", "primaryUses": [ "Historical: type 2 diabetes (superseded)" ], "typicalDose": { "range": null, "unit": null, "frequency": "weekly (early exploration)", "route": "subcutaneous", "notes": "Program-level data only." }, "evidenceLevel": "low", "sources": [ { "type": "manufacturer", "citation": "Hanmi Pharmaceutical pipeline disclosures (LAPSCOVERY GLP-1 program history)." } ], "interactionCoverage": "none-found", "related": [ "efpeglenatide", "exenatide" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "A discontinued drug: S0's own examples include discontinued drugs." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "A discontinued drug: S0's own examples include discontinued drugs." } ], "moleculeClass": "peptide-conjugate", "moleculeClassBasis": "conjugated to Fc" }, { "id": "lanreotide", "name": "Lanreotide", "aliases": [ "Somatuline Depot", "Somatuline Autogel" ], "tier": "mid", "category": "growth-hormone", "subcategory": "somatostatin analog", "class": "A synthetic cyclic octapeptide somatostatin analog, FDA-approved as a long-acting depot (Somatuline Depot) for acromegaly, gastroenteropancreatic neuroendocrine tumors, and carcinoid syndrome.", "tagline": "A long-acting somatostatin analogue injected every 28 days, sold as Somatuline Depot for acromegaly, gastroenteropancreatic neuroendocrine tumours and carcinoid syndrome. In the 204-patient CLARINET trial it more than halved the risk of progression or death, with 65% progression-free at 24 months against 33% on placebo.", "oneLiner": "A synthetic octapeptide somatostatin analogue given as a deep subcutaneous injection of 60 to 120 mg every 28 days (Somatuline Depot, Ipsen). Approved for acromegaly, advanced gastroenteropancreatic neuroendocrine tumours and carcinoid syndrome.", "sequence": "cyclic(D-2-Nal-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2) (disulfide Cys2–Cys7)", "molecularFormula": "C54H69N11O10S2", "molecularWeight": 1096.33, "halfLife": { "value": 26, "unit": "days", "range": "23 to 30 days (depot)", "source": { "type": "label", "ref": "Somatuline Depot prescribing information, section 12.3 (DailyMed version 16, effective October 11, 2024; read September 30, 2026)" } }, "fdaStatus": "approved", "approvalDetails": "Approved in the US as Somatuline Depot (lanreotide acetate injection) for acromegaly, gastroenteropancreatic neuroendocrine tumours and carcinoid syndrome; listed as a prescription drug on Drugs@FDA (openFDA, read September 30, 2026).", "mechanism": "Preferentially binds SSTR2 and SSTR5, inhibiting growth hormone, insulin-like growth factor 1, serotonin, and other neuroendocrine hormone release. The CLARINET trial established an antiproliferative benefit in GEP-NETs independent of hormone symptom control — extending use of somatostatin analogs from symptom management to tumor-stabilizing therapy.", "primaryUses": [ "Acromegaly (FDA-approved)", "Advanced gastroenteropancreatic neuroendocrine tumours (FDA-approved)", "Carcinoid syndrome (FDA-approved)" ], "typicalDose": { "range": "60–120", "unit": "mg", "frequency": "every 28 days", "route": "deep subcutaneous", "notes": "The tumour trials used 120 mg every 28 days." }, "evidenceLevel": "high", "sources": [ { "type": "fda", "citation": "FDA. Drugs@FDA (openFDA): SOMATULINE DEPOT (lanreotide acetate) injection, prescription. Read September 30, 2026." }, { "type": "pubmed", "citation": "Caplin ME, et al. \"Lanreotide in metastatic enteropancreatic neuroendocrine tumors.\" N Engl J Med, 2014;371(3):224-33. PMID: 25014687.", "pmid": "25014687" }, { "type": "pubmed", "citation": "Caplin ME, et al. \"Lanreotide autogel/depot in advanced enteropancreatic neuroendocrine tumours: final results of the CLARINET open-label extension study.\" Endocrine, 2021;71(2):502-513. PMID: 33052555.", "pmid": "33052555" }, { "type": "pubmed", "citation": "Gadelha MR, et al. \"Pasireotide versus continued treatment with octreotide or lanreotide in patients with inadequately controlled acromegaly (PAOLA): a randomised, phase 3 trial.\" Lancet Diabetes Endocrinol, 2014;2(11):875-84. PMID: 25260838.", "pmid": "25260838" }, { "type": "pubmed", "citation": "Mazziotti G, et al. \"Effects of lanreotide SR and Autogel on tumor mass in patients with acromegaly: a systematic review.\" Pituitary, 2010;13(1):60-7. PMID: 19189218.", "pmid": "19189218" }, { "type": "pubmed", "citation": "Joly D, et al. \"A three-year randomized, double-blind, placebo-controlled study of lanreotide in stage 2/3 autosomal dominant polycystic kidney disease.\" Kidney Int, 2026;110(4):988-999. PMID: 42320793.", "pmid": "42320793" }, { "type": "fda-pi", "citation": "Somatuline Depot (lanreotide acetate) injection Prescribing Information, sections 1 and 2 (DailyMed version 16, effective October 11, 2024; read September 30, 2026)." } ], "interactionCoverage": "partial", "related": [ "octreotide", "somatropin", "tesamorelin" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "larazotide", "name": "Larazotide", "aliases": [ "Larazotide acetate", "AT-1001", "INN-202" ], "tier": "mid", "category": "healing", "subcategory": "tight junction regulator", "class": "A synthetic octapeptide antagonist of zonulin — the endogenous regulator of intestinal tight-junction permeability.", "tagline": "An oral tight-junction regulator peptide (AT-1001) tested in coeliac disease: it eased symptoms at some doses but never changed its permeability marker, and its phase 3 trial was terminated by the sponsor in 2022. Not approved.", "oneLiner": "A synthetic eight-amino-acid peptide (AT-1001) designed to keep intestinal tight junctions from opening, tested by mouth in coeliac disease. It eased symptoms at some doses without changing permeability, and its phase 3 trial (NCT03569007) was terminated by the sponsor in 2022.", "sequence": "Gly-Gly-Val-Leu-Val-Gln-Pro-Gly", "molecularFormula": "C32H55N9O10", "molecularWeight": "725.8", "halfLife": { "value": null, "unit": null, "range": "Not established", "notes": "Taken by mouth to act on the gut lining.", "source": { "type": "qualitative", "note": "a description with no figure; no half-life measurement is cited for it" } }, "fdaStatus": "clinical-trials", "approvalDetails": "Not approved; Drugs@FDA holds no application (openFDA, read September 30, 2026). ClinicalTrials.gov lists phase 3 trial NCT03569007 as terminated by the sponsor (record updated July 26, 2022).", "mechanism": "Blocks zonulin-mediated disassembly of intestinal tight junctions, maintaining epithelial barrier integrity. Prevents paracellular passage of gluten-derived peptides and other luminal antigens that would otherwise trigger mucosal inflammation. Administered orally and acts within the intestinal lumen.", "primaryUses": [ "Coeliac disease (investigational, alongside a gluten-free diet)", "Post-COVID multisystem inflammatory syndrome in children (phase 2a trial)" ], "typicalDose": { "range": "0.25–8", "unit": "mg", "frequency": "three times daily", "route": "oral", "notes": "The range tested; only 0.5 mg met its primary end point in the largest trial." }, "evidenceLevel": "medium", "sources": [ { "type": "fda", "citation": "FDA. Drugs@FDA (openFDA): no application for larazotide. Read September 30, 2026." }, { "type": "other", "citation": "ClinicalTrials.gov. NCT03569007: Study to Evaluate the Efficacy and Safety of Larazotide Acetate for the Relief of CeD Symptoms. Status: Terminated (trial terminated by sponsor); record updated July 26, 2022. Read September 30, 2026." }, { "type": "pubmed", "citation": "Leffler DA, et al. \"Larazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial.\" Gastroenterology, 2015;148(7):1311-9.e6. PMID: 25683116.", "pmid": "25683116" }, { "type": "pubmed", "citation": "Kelly CP, et al. \"Larazotide acetate in patients with coeliac disease undergoing a gluten challenge: a randomised placebo-controlled study.\" Aliment Pharmacol Ther, 2013;37(2):252-62. PMID: 23163616.", "pmid": "23163616" }, { "type": "pubmed", "citation": "Leffler DA, et al. \"A randomized, double-blind study of larazotide acetate to prevent the activation of celiac disease during gluten challenge.\" Am J Gastroenterol, 2012;107(10):1554-62. PMID: 22825365.", "pmid": "22825365" }, { "type": "pubmed", "citation": "Paterson BM, et al. \"The safety, tolerance, pharmacokinetic and pharmacodynamic effects of single doses of AT-1001 in coeliac disease subjects: a proof of concept study.\" Aliment Pharmacol Ther, 2007;26(5):757-66. PMID: 17697209.", "pmid": "17697209" }, { "type": "pubmed", "citation": "Yonker LM, et al. \"Viral spike antigen clearance and augmented recovery in children with post-COVID multisystem inflammatory syndrome treated with larazotide.\" Sci Transl Med, 2025;17(809):eadu4284. PMID: 40737433.", "pmid": "40737433" }, { "type": "pubmed", "citation": "Hoilat GJ, et al. \"Larazotide acetate for treatment of celiac disease: A systematic review and meta-analysis of randomized controlled trials.\" Clin Res Hepatol Gastroenterol, 2022;46(1):101782. PMID: 34339872.", "pmid": "34339872" }, { "type": "other", "citation": "9 Meters Biopharma, press release (SEC 8-K exhibit 99.1), June 21, 2022: an interim analysis of the phase 3 CedLara trial does not support continuing it. Read September 30, 2026." } ], "interactionCoverage": "none-found", "related": [ "bpc-157", "kpv", "ll-37" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." } ], "moleculeClass": "peptide" }, { "id": "leuphasyl", "name": "Leuphasyl", "aliases": [ "Pentapeptide-18", "Tyr-D-Ala-Gly-Phe-Leu" ], "tier": "stub", "category": "cosmetic", "subcategory": "topical cosmetic peptide (enkephalin analog)", "class": "A synthetic pentapeptide modeled on leucine-enkephalin, formulated as a topical cosmetic ingredient.", "tagline": "A cosmetic-ingredient pentapeptide modeled on leucine-enkephalin — marketed by Lipotec as a post-synaptic adjunct to Argireline-class pre-synaptic peptides for expression-line reduction.", "oneLiner": "A synthetic enkephalin analog (Tyr-D-Ala-Gly-Phe-Leu) developed by Lipotec as a cosmetic ingredient, proposed to reduce acetylcholine release at the neuromuscular junction through a δ-opioid receptor-mediated pathway on motor neurons.", "sequence": "Tyr-D-Ala-Gly-Phe-Leu", "molecularFormula": "C30H41N5O7", "molecularWeight": 583.68, "halfLife": { "value": null, "unit": null, "range": "topical only", "notes": "Systemic absorption from topical cosmetic formulations is minimal." }, "fdaStatus": "research-only", "approvalDetails": "Cosmetic ingredient; not a drug.", "mechanism": "Proposed to act at δ-opioid receptors on motor neuron terminals to reduce acetylcholine release. Manufacturer claims are that the mechanism is complementary to Argireline's SNAP-25 competitive inhibition, and that the combination produces additive expression-line reduction.", "primaryUses": [ "Topical cosmetic anti-aging formulations (expression-line reduction)" ], "typicalDose": { "range": "2–5", "unit": "% (topical formulation)", "frequency": "daily topical application", "route": "topical", "notes": "Often co-formulated with Argireline." }, "evidenceLevel": "low", "sources": [ { "type": "manufacturer", "citation": "Lipotec. \"Leuphasyl technical data sheet and cosmetic ingredient profile.\"" } ], "interactionCoverage": "unreviewed", "related": [ "argireline", "syn-ake", "snap-8" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." } ], "moleculeClass": "peptide" }, { "id": "leuprolide", "name": "Leuprolide", "aliases": [ "Lupron", "Lupron Depot", "Eligard", "Fensolvi", "Camcevi", "leuprorelin" ], "tier": "full", "category": "sexual-health", "subcategory": "GnRH agonist", "class": "Synthetic nonapeptide GnRH agonist, the prototype long-acting GnRH analogue: continuous exposure suppresses pituitary gonadotropin and downstream sex-steroid production after an initial flare.", "tagline": "The prototypical long-acting GnRH agonist: after a brief flare it shuts down testosterone and oestrogen, FDA-approved since 1985 in forms from a daily pen to six-month depots for prostate cancer, endometriosis, fibroids and central precocious puberty.", "oneLiner": "A synthetic nonapeptide GnRH agonist (GnRH with D-Leu at position 6 and an ethylamide in place of the tenth residue) that, given continuously, first stimulates and then suppresses pituitary gonadotropin release and downstream testosterone and oestrogen. Marketed as Lupron Depot (1- to 6-month intramuscular depots), Eligard (subcutaneous gel depot), Lupron Depot-Ped, Fensolvi, Camcevi, the daily Vobrig pen and generic injections.", "sequence": "pGlu-His-Trp-Ser-Tyr-D-Leu-Leu-Arg-Pro-NHEt", "molecularFormula": "C59H84N16O12", "molecularWeight": 1209.4, "halfLife": { "value": 3, "unit": "hours", "range": "about 3 h terminal after an IV bolus (two-compartment model); depots release it over 1–6 months", "notes": "From the Lupron Depot label (healthy male volunteers; clearance 7.6 L/h, volume of distribution 27 L)." }, "fdaStatus": "approved", "approvalDetails": "FDA-approved (Drugs@FDA, read September 28, 2026): Lupron injection (NDA 019010, April 9, 1985; now discontinued); Lupron Depot (NDA 019732, January 26, 1989) for advanced prostate cancer (7.5, 22.5, 30 and 45 mg) and, at 3.75 and 11.25 mg, for endometriosis and preoperative fibroids; Lupron Depot-Ped (1993), Fensolvi (2020) and Vobrig (daily pen, NDA 213225, August 26, 2026) for central precocious puberty; Eligard (2002) and Camcevi (2021) for prostate cancer; generic leuprolide acetate injections.", "mechanism": "Binds the pituitary GnRH receptor as an agonist. At the start gonadotropins and sex steroids rise (testosterone about 50% above baseline per the label); continuous exposure then suppresses ovarian and testicular steroid production, reversibly on stopping. With depot dosing testosterone reached castrate levels by about three weeks (median 22 days on the 30 mg four-month depot).", "primaryUses": [ "Advanced prostate cancer (androgen deprivation)", "Endometriosis, with norethindrone add-back", "Uterine fibroids before surgery (with iron)", "Central precocious puberty", "Off-label: ovarian suppression in premenopausal breast cancer; puberty suppression in transgender and gender-diverse youth" ], "typicalDose": { "range": "varies by formulation", "unit": "", "frequency": "daily SC pen to 6-month depot", "route": "subcutaneous or intramuscular", "notes": "Lupron Depot, prostate cancer: 7.5 mg every 4 weeks, 22.5 mg every 12 weeks, 30 mg every 16 weeks or 45 mg every 24 weeks, intramuscularly. Endometriosis: 3.75 mg monthly for up to 6 months; retreatment only with norethindrone add-back, 12 months in total. Fibroids: 3.75 mg monthly with iron for up to 3 months. Vobrig (central precocious puberty): weight-based daily subcutaneous doses of 0.8–2 mg per pen dose." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Lupron Depot (leuprolide acetate for depot suspension) 7.5 mg, 22.5 mg, 30 mg, 45 mg Prescribing Information. AbbVie (DailyMed version of 2026-06-18, read 2026-09-28)." }, { "type": "fda-pi", "citation": "Lupron Depot 3.75 mg and 11.25 mg (endometriosis, fibroids) Prescribing Information. AbbVie (DailyMed versions of 2025-09, read 2026-09-28)." }, { "type": "fda-pi", "citation": "Vobrig (leuprolide acetate) injection Prescribing Information. Sun Pharmaceutical Industries; NDA 213225, approved August 26, 2026 (read 2026-09-28)." }, { "type": "fda-pi", "citation": "US FDA, Drugs@FDA: leuprolide acetate applications including Lupron NDA 019010 (1985), Lupron Depot NDA 019732 (1989), Lupron Depot-Ped NDA 020263 (1993), Eligard NDA 021343 (2002), Fensolvi NDA 213150 (2020), Camcevi NDA 211488 (2021) and Vobrig NDA 213225 (2026) (read 2026-09-28)." }, { "type": "Human", "citation": "Rizzo M, et al. \"Leuprorelin acetate depot in advanced prostatic cancer: a phase II multicentre trial.\" J Int Med Res, 1990;18 Suppl 1:114-25. PMID: 2108883.", "pmid": "2108883" }, { "type": "Human", "citation": "Sharifi R, et al. \"Leuprolide acetate (30-mg depot every four months) in the treatment of advanced prostate cancer.\" Urology, 1998;51(2):271-6. PMID: 9495710.", "pmid": "9495710" }, { "type": "Review", "citation": "Sartor O. \"Eligard: leuprolide acetate in a novel sustained-release delivery system.\" Urology, 2003;61(2 Suppl 1):25-31. PMID: 12667884.", "pmid": "12667884" }, { "type": "Review", "citation": "Berges R, et al. \"Effect of a new leuprorelin formulation on testosterone levels in patients with advanced prostate cancer.\" Curr Med Res Opin, 2006;22(4):649-55. PMID: 16684425.", "pmid": "16684425" }, { "type": "Human", "citation": "Tutrone R, et al. \"Testosterone Recovery for Relugolix Versus Leuprolide in Men with Advanced Prostate Cancer: Results from the Phase 3 HERO Study.\" Eur Urol Oncol, 2024;7(4):906-913. PMID: 38143206.", "pmid": "38143206" }, { "type": "Human", "citation": "Soloway MS, et al. \"Randomized prospective study comparing radical prostatectomy alone versus radical prostatectomy preceded by androgen blockade in clinical stage B2 (T2bNxM0) prostate cancer. The Lupron Depot Neoadjuvant Prostate Cancer Study Group.\" J Urol, 1995;154(2 Pt 1):424-8. PMID: 7541859.", "pmid": "7541859" }, { "type": "Human", "citation": "Shore ND, et al. \"Enzalutamide with or without leuprolide in patients with high-risk biochemically recurrent prostate cancer: EMBARK post hoc analysis by age.\" Eur J Cancer, 2026;232:116110. PMID: 41274168.", "pmid": "41274168" }, { "type": "Human", "citation": "Ohlmann CH, et al. \"Efficacy and Tolerability of Leuprorelin Acetate (Eligard®) in Daily Practice in Germany: Pooled Data from 2 Prospective, Non-Interventional Studies with 3- or 6-Month Depot Formulations in Patients with Advanced Prostate Cancer.\" Urol Int, 2018;100(1):66-71. PMID: 29197875.", "pmid": "29197875" }, { "type": "Human", "citation": "Villalba-Cuesta PL, et al. \"Interstitial pneumonitis associated with leuprorelin acetate for a prostate cancer: A case report.\" J Oncol Pharm Pract, 2022;28(8):1910-1913. PMID: 35234109.", "pmid": "35234109" }, { "type": "Human", "citation": "Hornstein MD, et al. \"Leuprolide acetate depot and hormonal add-back in endometriosis: a 12-month study. Lupron Add-Back Study Group.\" Obstet Gynecol, 1998;91(1):16-24. PMID: 9464714.", "pmid": "9464714" }, { "type": "Human", "citation": "Wheeler JM, et al. \"Depot leuprolide acetate versus danazol in the treatment of women with symptomatic endometriosis: a multicenter, double-blind randomized clinical trial. II. Assessment of safety. The Lupron Endometriosis Study Group.\" Am J Obstet Gynecol, 1993;169(1):26-33. PMID: 8333471.", "pmid": "8333471" }, { "type": "Human", "citation": "Donnez J, et al. \"Ulipristal acetate versus leuprolide acetate for uterine fibroids.\" N Engl J Med, 2012;366(5):421-32. PMID: 22296076.", "pmid": "22296076" }, { "type": "Human", "citation": "Kendzierski DC, et al. \"Efficacy of Different Leuprolide Administration Schedules in Premenopausal Breast Cancer: A Retrospective Review.\" Clin Breast Cancer, 2018;18(5):e939-e942. PMID: 29747931.", "pmid": "29747931" }, { "type": "Human", "citation": "Kurebayashi J, et al. \"A follow-up study of a randomized controlled study evaluating safety and efficacy of leuprorelin acetate every-3-month depot for 2 versus 3 or more years with tamoxifen for 5 years as adjuvant treatment in premenopausal patients with endocrine-responsive breast cancer.\" Breast Cancer, 2021;28(3):684-697. PMID: 33638810.", "pmid": "33638810" }, { "type": "Human", "citation": "Helvacioglu D, et al. \"Utility of a 40-minute LH level after depot leuprolide for diagnosis and treatment monitoring in girls with CPP.\" J Endocrinol Invest, 2026;49(9):2375-2383. PMID: 42189483.", "pmid": "42189483" }, { "type": "Human", "citation": "Eitel KB, et al. \"Leuprolide Acetate for Puberty Suppression in Transgender and Gender Diverse Youth: A Comparison of Subcutaneous Eligard Versus Intramuscular Lupron.\" J Adolesc Health, 2023;72(2):307-311. PMID: 36404242.", "pmid": "36404242" }, { "type": "In Vitro", "citation": "Zhou J, et al. \"Reverse Engineering the 1-Month Lupron Depot®.\" AAPS J, 2018;20(6):105. PMID: 30280294.", "pmid": "30280294" } ], "interactionCoverage": "partial", "related": [ "triptorelin", "goserelin", "histrelin", "degarelix", "gonadorelin" ], "lastReviewed": "2026-09-28", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.2.1", "named": true, "wording": "leuprorelin", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "malesOnly": true, "monitoring": "GnRH analogues in female athletes under 18, in and out of competition" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.2.1", "named": true, "wording": "leuprorelin", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "malesOnly": true, "monitoring": "GnRH analogues in female athletes under 18, in and out of competition" } ], "moleculeClass": "peptide" }, { "id": "linaclotide", "name": "Linaclotide", "aliases": [ "Linzess", "Constella (EU)", "MD-1100", "MM-416775" ], "tier": "mid", "category": "healing", "subcategory": "Guanylate cyclase-C agonist", "class": "A 14-amino-acid synthetic peptide guanylate cyclase-C (GC-C) agonist approved in the United States and Europe for treatment of irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC).", "tagline": "An oral peptide that works inside the bowel, approved for IBS with constipation and for constipation from the age of two.", "oneLiner": "A 14-amino-acid guanylate cyclase-C agonist swallowed as a capsule, which pulls fluid into the intestine and eases IBS pain.", "sequence": "Cys-Cys-Glu-Tyr-Cys-Cys-Asn-Pro-Ala-Cys-Thr-Gly-Cys-Tyr (cyclic, three disulfide bonds: Cys1-Cys6, Cys2-Cys10, Cys5-Cys13)", "molecularFormula": "C59H79N15O21S6", "molecularWeight": 1526.74, "halfLife": { "value": null, "unit": null, "range": "Not systemically absorbed; acts luminally", "notes": "Linaclotide and its active metabolite (MM-419447, the 13-residue des-tyrosine form) are essentially not detectable in plasma at therapeutic doses; drug is degraded by intestinal proteases with minimal systemic exposure.", "source": { "type": "qualitative", "note": "a description with no figure; no half-life measurement is cited for it" } }, "fdaStatus": "approved", "approvalDetails": "FDA-approved as Linzess (linaclotide) capsules, AbbVie, NDA 202811. The current label covers IBS-C in adults and in children 7 and over, chronic idiopathic constipation in adults, and functional constipation in children from age 2, with a boxed warning contraindicating use under 2 years.", "mechanism": "Binds guanylate cyclase-C (GC-C) on the luminal (apical) surface of intestinal epithelial cells, mimicking the endogenous ligands guanylin and uroguanylin. Activation of GC-C increases intracellular cGMP, which activates protein kinase G II (PKG II) and phosphorylates the CFTR chloride channel, increasing luminal secretion of chloride and (via anion-exchange transporters) bicarbonate. Water follows the osmotic gradient into the lumen, softening stool and accelerating transit. Increased cGMP also has a direct visceral-analgesic effect on submucosal afferent nociceptive neurons, which accounts for linaclotide's effect on IBS-C abdominal pain. Mechanism is luminal and local; systemic absorption is negligible.", "primaryUses": [ "IBS with constipation in adults and children 7 and over", "Chronic idiopathic constipation in adults", "Functional constipation in children from age 2" ], "typicalDose": { "range": "72, 145, or 290", "unit": "mcg", "frequency": "once daily on an empty stomach", "route": "oral", "notes": "Adult CIC: 145 mcg once daily (72 mcg option available for patients who prefer a lower starting dose). Adult IBS-C: 290 mcg once daily. Pediatric functional constipation (6–17): 72 mcg once daily. Take at least 30 minutes before the first meal of the day. Contraindicated in patients <2 years. Most common adverse event is diarrhea (which leads to discontinuation in ~5% of patients)." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Linzess (linaclotide) capsules Prescribing Information, boxed warning and sections 1 and 2. AbbVie (DailyMed version 39, effective May 21, 2026; read September 30, 2026)." }, { "type": "pubmed", "citation": "Chey WD, et al. \"Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety.\" Am J Gastroenterol, 2012;107(11):1702-12. PMID: 22986437.", "pmid": "22986437" }, { "type": "pubmed", "citation": "Lembo AJ, et al. \"Two randomized trials of linaclotide for chronic constipation.\" N Engl J Med, 2011;365(6):527-36. PMID: 21830967.", "pmid": "21830967" }, { "type": "pubmed", "citation": "Di Lorenzo C, et al. \"Efficacy and safety of linaclotide in treating functional constipation in paediatric patients: a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial.\" Lancet Gastroenterol Hepatol, 2024;9(3):238-250. PMID: 38211604.", "pmid": "38211604" }, { "type": "pubmed", "citation": "Fukudo S, et al. \"A randomized controlled and long-term linaclotide study of irritable bowel syndrome with constipation patients in Japan.\" Neurogastroenterol Motil, 2018;30(12):e13444. PMID: 30136447.", "pmid": "30136447" }, { "type": "pubmed", "citation": "Weinberg DS, et al. \"Bioactivity of Oral Linaclotide in Human Colorectum for Cancer Chemoprevention.\" Cancer Prev Res (Phila), 2017;10(6):345-354. PMID: 28396341.", "pmid": "28396341" }, { "type": "other", "citation": "US FDA, Drugs@FDA (openFDA): LINZESS (linaclotide), NDA 202811, AbbVie, prescription. Read September 30, 2026." } ], "interactionCoverage": "label", "related": [ "plecanatide" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "liraglutide", "name": "Liraglutide", "aliases": [ "Victoza", "Saxenda", "NN2211" ], "tier": "full", "category": "metabolic", "subcategory": "GLP-1 receptor agonist", "class": "Daily GLP-1 receptor agonist with a C16 fatty acid side chain for albumin binding.", "tagline": "The first once-daily GLP-1 analog to be FDA-approved for both type 2 diabetes (Victoza) and chronic weight management (Saxenda).", "oneLiner": "A 31-amino-acid synthetic GLP-1 analog with 97% sequence homology to native GLP-1, modified with a palmitoyl (C16) fatty acid at Lys26 to extend half-life to roughly 13 hours.", "sequence": "HAEGTFTSDVSSYLEGQAAKEFIAWLVRGRG (with γGlu-C16 at Lys26)", "molecularFormula": "C172H265N43O51", "molecularWeight": 3751.2, "halfLife": { "value": 13, "unit": "hours", "range": "~13 hours", "notes": "Albumin-binding fatty acid side chain supports once-daily subcutaneous dosing." }, "fdaStatus": "approved", "approvalDetails": "FDA-approved as Victoza (T2DM, 2010) and Saxenda (chronic weight management, 2014). Manufactured by Novo Nordisk. Generic liraglutide approved in 2024.", "mechanism": "Agonist at the GLP-1 receptor. Enhances glucose-dependent insulin secretion, suppresses glucagon, slows gastric emptying, and acts on hypothalamic appetite centers. The daily dosing requirement reflects its shorter half-life compared with semaglutide — which also means faster onset and offset of both therapeutic and adverse effects.", "primaryUses": [ "Type 2 diabetes mellitus (Victoza)", "Chronic weight management (Saxenda, BMI ≥30 or ≥27 with comorbidity)", "Pediatric obesity (Saxenda, ≥12 years)", "Cardiovascular risk reduction in T2DM with established CVD (LEADER trial)" ], "typicalDose": { "range": "0.6–3.0", "unit": "mg", "frequency": "once daily", "route": "subcutaneous", "notes": "Victoza titrated 0.6 → 1.2 → 1.8 mg daily over 2 weeks. Saxenda titrated 0.6 → 3.0 mg daily over 5 weeks to minimize GI side effects." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Victoza (liraglutide) Prescribing Information. Novo Nordisk." }, { "type": "fda-pi", "citation": "Saxenda (liraglutide) Prescribing Information. Novo Nordisk." }, { "type": "clinical-trial", "citation": "Pi-Sunyer X, et al. \"A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management (SCALE).\" N Engl J Med, 2015;373:11-22. PMID: 26132939.", "pmid": "26132939" }, { "type": "clinical-trial", "citation": "Marso SP, et al. \"Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes (LEADER).\" N Engl J Med, 2016;375:311-322. PMID: 27295427.", "pmid": "27295427" }, { "type": "pubmed", "citation": "Rubino DM, et al. \"Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial.\" JAMA, 2022;327(2):138-150. PMID: 35015037.", "pmid": "35015037" }, { "type": "pubmed", "citation": "Drucker DJ. \"GLP-1 physiology informs the pharmacotherapy of obesity.\" Mol Metab, 2022;57:101351. PMID: 34626851.", "pmid": "34626851" }, { "type": "pubmed", "citation": "Kelly AS, et al. \"A Randomized, Controlled Trial of Liraglutide for Adolescents with Obesity.\" N Engl J Med, 2020;382(22):2117-2128. PMID: 32233338.", "pmid": "32233338" }, { "type": "pubmed", "citation": "Mann JFE, et al. \"Liraglutide and Renal Outcomes in Type 2 Diabetes.\" N Engl J Med, 2017;377(9):839-848. PMID: 28854085.", "pmid": "28854085" }, { "type": "pubmed", "citation": "Davies MJ, et al. \"Efficacy of Liraglutide for Weight Loss Among Patients With Type 2 Diabetes: The SCALE Diabetes Randomized Clinical Trial.\" JAMA, 2015;314(7):687-99. PMID: 26284720.", "pmid": "26284720" }, { "type": "pubmed", "citation": "Buse JB, et al. \"Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6).\" Lancet, 2009;374(9683):39-47. PMID: 19515413.", "pmid": "19515413" } ], "interactionCoverage": "partial", "related": [ "semaglutide", "tirzepatide", "dulaglutide", "exenatide" ], "lastReviewed": "2026-04-18", "publishedAt": "2026-04-18", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "livagen", "name": "Livagen", "aliases": [ "Lys-Glu-Asp-Ala", "KEDA" ], "tier": "stub", "category": "longevity", "subcategory": "Khavinson short-chain bioregulator (hepatic / lymphoid)", "class": "A synthetic short tetrapeptide developed by the Khavinson group as a \"hepatic bioregulator\" with reported lymphoid-cell effects.", "tagline": "A Khavinson tetrapeptide proposed to support hepatic and lymphocyte function; reported to decondense chromatin in aged lymphocytes in in-vitro studies — Russian-language evidence, no Western replication.", "oneLiner": "A Khavinson-group short tetrapeptide (Lys-Glu-Asp-Ala) proposed to act on lymphoid and hepatic tissues, with in-vitro reports of chromatin decondensation and restoration of gene-expression patterns in aged lymphocytes.", "sequence": "Lys-Glu-Asp-Ala", "molecularFormula": "C18H32N6O8", "molecularWeight": 460.48, "halfLife": { "value": null, "unit": null, "range": "undetermined", "notes": "Pharmacokinetics not characterized in Western-standard studies." }, "fdaStatus": "research-only", "approvalDetails": "Not FDA-approved. Marketed in Russia as a bioregulator supplement.", "mechanism": "Khavinson-group in-vitro studies report that Livagen causes chromatin decondensation in aged lymphocytes and restores transcriptional activity at heterochromatin regions that become silenced with age. The hypothesized in-vivo effect is restoration of immune-cell gene expression in aged animals.", "primaryUses": [ "Investigational support for hepatic and immune aging (Russian literature)", "Research into chromatin aging" ], "typicalDose": { "range": "not established", "unit": null, "frequency": "not established", "route": "oral (capsule)", "notes": "Typical supplement protocols use 10 mg daily for 10–20 days." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Khavinson VK, et al. \"Activating effect of peptides Lys-Glu-Asp-Ala and Ala-Glu-Asp-Gly on chromatin of old lymphocytes.\" Bull Exp Biol Med, 2011;150:505-507." }, { "type": "review", "citation": "Khavinson VK, Malinin VV. \"Gerontological aspects of genome peptide regulation.\" Karger AG, Basel, 2005." } ], "interactionCoverage": "none-found", "related": [ "epithalon", "ovagen", "thymulin" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "lixisenatide", "name": "Lixisenatide", "aliases": [ "Adlyxin", "Lyxumia", "AVE0010" ], "tier": "mid", "category": "metabolic", "subcategory": "GLP-1 receptor agonist", "class": "Short-acting daily GLP-1 receptor agonist, an analog of exendin-4 with C-terminal modifications.", "tagline": "A short-acting, prandial GLP-1 agonist primarily used to target postprandial glucose excursions.", "oneLiner": "A 44-amino-acid exendin-4 derivative with six additional lysine residues at the C-terminus, giving a shorter half-life (~3 hours) that favors postprandial glucose control.", "sequence": "HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPSKKKKKK", "molecularFormula": "C215H347N61O65S", "molecularWeight": 4858.5, "halfLife": { "value": null, "unit": null, "range": "not reported in the sources read", "source": { "type": "none", "note": "searched PubMed on October 1, 2026; no human half-life figure in the sources read" } }, "fdaStatus": "approved", "approvalDetails": "Adlyxin, BLA 208471, approved July 27, 2016; the fixed-ratio combination with insulin glargine, Soliqua 100/33, BLA 208673, November 21, 2016 (Drugs@FDA, read October 1, 2026). Use in Parkinson's disease is investigational.", "mechanism": "GLP-1 receptor agonism with emphasis on delayed gastric emptying — producing stronger postprandial glucose suppression than longer-acting agents at equivalent exposures. The short half-life means glucagon suppression and satiety effects are confined to the immediate postprandial period.", "primaryUses": [ "Type 2 diabetes mellitus — primarily postprandial glucose control", "Combination therapy with basal insulin (Soliqua)" ], "typicalDose": { "range": null, "unit": null, "frequency": "once daily", "route": "subcutaneous", "notes": "Once daily, and also sold in a fixed-ratio combination with insulin glargine. Its Parkinson's use is investigational and not a dosing recommendation." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Pfeffer MA, et al. \"Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome.\" N Engl J Med, 2015;373(23):2247-57. PMID: 26630143.", "pmid": "26630143" }, { "type": "pubmed", "citation": "Meissner WG, et al. \"Trial of Lixisenatide in Early Parkinson's Disease.\" N Engl J Med, 2024;390(13):1176-1185. PMID: 38598572.", "pmid": "38598572" }, { "type": "pubmed", "citation": "Liu F, et al. \"Efficacy of once-daily glucagon-like peptide-1 receptor agonist lixisenatide as an add-on treatment to basal insulin in Asian and white adults with type 2 diabetes mellitus: An individual-level pooled analysis of phase III studies.\" J Diabetes Investig, 2021;12(8):1386-1394. PMID: 33475222.", "pmid": "33475222" }, { "type": "pubmed", "citation": "Terauchi Y, et al. \"Efficacy and safety of insulin glargine/lixisenatide fixed-ratio combination (iGlarLixi 1:1) in Japanese patients with type 2 diabetes mellitus inadequately controlled on oral antidiabetic drugs: A randomized, 26-week, open-label, multicentre study: The LixiLan JP-O2 randomized clinical trial.\" Diabetes Obes Metab, 2020;22 Suppl 4:14-23. PMID: 32291880.", "pmid": "32291880" }, { "type": "pubmed", "citation": "Whyte MB, et al. \"Lixisenatide Reduces Chylomicron Triacylglycerol by Increased Clearance.\" J Clin Endocrinol Metab, 2019;104(2):359-368. PMID: 30215735.", "pmid": "30215735" }, { "type": "fda-pi", "citation": "Adlyxin (lixisenatide) Prescribing Information. Sanofi." } ], "interactionCoverage": "studied", "related": [ "exenatide", "liraglutide" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-18", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "lixivaptan", "name": "Lixivaptan", "aliases": [ "Jinarc Alternative", "VPA-985" ], "tier": "mid", "category": "cardiovascular", "subcategory": "vasopressin antagonist", "class": "An oral selective V2 vasopressin receptor antagonist (aquaretic) for hyponatremia and polycystic kidney disease.", "tagline": "An oral vasopressin V2 blocker, not a peptide, that raised sodium in hyponatraemia trials and was discontinued in June 2022.", "oneLiner": "A small-molecule vasopressin V2 receptor antagonist related to tolvaptan, which makes the kidneys release free water.", "sequence": "Non-peptide small molecule (vasopressin V2 receptor antagonist)", "molecularFormula": "C27H29ClN4O2", "molecularWeight": 476.0, "halfLife": { "value": null, "unit": null, "range": "not reported in the sources read", "source": { "type": "none", "note": "searched PubMed on September 30, 2026; no half-life reported" } }, "fdaStatus": "discontinued", "approvalDetails": "Never approved. Centessa discontinued development for autosomal dominant polycystic kidney disease on June 2, 2022, ending its phase 3 ACTION and open-label ALERT studies after liver enzyme elevations in one ALERT patient; development for hyponatraemia had already ended.", "mechanism": "Selectively blocks the vasopressin V2 receptor on principal cells of the renal collecting duct, preventing aquaporin-2 insertion into the apical membrane. This blocks ADH-mediated water reabsorption, promoting excretion of free water (aquaresis) without affecting sodium, potassium, or other electrolytes. In ADPKD, V2 receptor blockade also reduces cAMP-driven cyst growth.", "primaryUses": [ "Hyponatraemia (phase 3, development ended)", "Polycystic kidney disease (development stopped 2022)" ], "typicalDose": { "range": "25–100", "unit": "mg", "frequency": "twice daily", "route": "oral", "notes": "Investigational dosing. Tolvaptan (approved V2 antagonist) dosed at 15–60 mg/day for comparison." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "Abraham WT, et al. \"Lixivaptan safely and effectively corrects serum sodium concentrations in hospitalized patients with euvolemic hyponatremia.\" Kidney Int, 2012;82(11):1223-30. PMID: 22932119.", "pmid": "22932119" }, { "type": "pubmed", "citation": "Abraham WT, et al. \"Oral lixivaptan effectively increases serum sodium concentrations in outpatients with euvolemic hyponatremia.\" Kidney Int, 2012;82(11):1215-22. PMID: 22932122.", "pmid": "22932122" }, { "type": "pubmed", "citation": "Ghali JK, et al. \"The efficacy and safety of lixivaptan in outpatients with heart failure and volume overload: results of a multicentre, randomized, double-blind, placebo-controlled, parallel-group study.\" Eur J Heart Fail, 2012;14(6):642-51. PMID: 22510424.", "pmid": "22510424" }, { "type": "pubmed", "citation": "Abraham WT, et al. \"Aquaretic effect of lixivaptan, an oral, non-peptide, selective V2 receptor vasopressin antagonist, in New York Heart Association functional class II and III chronic heart failure patients.\" J Am Coll Cardiol, 2006;47(8):1615-21. PMID: 16630999.", "pmid": "16630999" }, { "type": "other", "citation": "Centessa Pharmaceuticals plc, Form 8-K and press release, June 2, 2022: strategic decision to discontinue clinical development of lixivaptan for ADPKD. Read September 30, 2026." }, { "type": "clinicaltrials", "citation": "ClinicalTrials.gov NCT04064346: ACTION, the phase 3 trial of lixivaptan in autosomal dominant polycystic kidney disease, ended when development stopped (registry record read September 30, 2026)." } ], "interactionCoverage": "none-found", "related": [ "vasopressin", "desmopressin", "terlipressin" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-20", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S5", "named": false, "wording": "Vaptans, e.g. conivaptan, mozavaptan, tolvaptan", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "A vaptan: S5 names the class and three of its members." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S5", "named": false, "wording": "Vaptans, e.g. conivaptan, mozavaptan, tolvaptan", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "A vaptan: S5 names the class and three of its members." } ], "moleculeClass": "small-molecule", "statusVerified": "2026-09-30", "moleculeClassBasis": "small-molecule" }, { "id": "ll-37", "name": "LL-37", "aliases": [ "Cathelicidin LL-37", "human cationic antimicrobial protein 18 (hCAP18)", "CAMP" ], "tier": "full", "category": "healing", "subcategory": "antimicrobial/immunomodulatory peptide", "class": "The only human cathelicidin — a 37-amino-acid antimicrobial host-defense peptide with broad immunomodulatory activity.", "tagline": "The only human cathelicidin — an antimicrobial peptide with direct activity against bacteria, fungi, viruses, and biofilms, with additional roles in wound healing and immune signaling.", "oneLiner": "The 37-residue active peptide released from the human cathelicidin precursor hCAP-18 (encoded by the CAMP gene), with direct microbicidal activity and pleiotropic effects on wound healing, angiogenesis, and innate immune signaling.", "sequence": "LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES", "molecularFormula": "C205H340N60O53", "molecularWeight": 4493.33, "halfLife": { "value": null, "unit": null, "range": "undetermined", "notes": "Rapid proteolytic degradation systemically; active primarily in local tissue compartments." }, "fdaStatus": "research-only", "approvalDetails": "Not approved anywhere. Tested topically in chronic leg and foot ulcers (a phase IIb leg-ulcer trial missed its primary endpoint) and, as an oral recombinant product, in one COVID-19 trial. Excess, abnormally processed cathelicidin is implicated in rosacea inflammation.", "mechanism": "Direct antimicrobial activity via membrane disruption of gram-positive and gram-negative bacteria, fungi, and enveloped viruses. Modulates macrophage polarization, neutralizes LPS, promotes keratinocyte migration, and stimulates angiogenesis via FPRL1 receptor activation. Abnormally elevated in rosacea and some psoriasis phenotypes (pathogenic at high local concentrations).", "primaryUses": [ "Chronic wound research", "Antimicrobial / biofilm research", "Community use for chronic infection in functional-medicine settings" ], "typicalDose": { "range": "100–500", "unit": "mcg", "frequency": "daily or every other day", "route": "subcutaneous (community); topical (research)", "notes": "Community dosing only; no clinical standard. High doses have been associated with flushing and pro-inflammatory effects." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Grönberg A, et al. \"Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial.\" Wound Repair Regen, 2014;22(5):613-21. PMID: 25041740.", "pmid": "25041740" }, { "type": "pubmed", "citation": "Mahlapuu M, et al. \"Evaluation of LL-37 in healing of hard-to-heal venous leg ulcers: A multicentric prospective randomized placebo-controlled clinical trial.\" Wound Repair Regen, 2021;29(6):938-950. PMID: 34687253.", "pmid": "34687253" }, { "type": "pubmed", "citation": "Miranda E, et al. \"Efficacy of LL-37 cream in enhancing healing of diabetic foot ulcer: a randomized double-blind controlled trial.\" Arch Dermatol Res, 2023;315(9):2623-2633. PMID: 37480520.", "pmid": "37480520" }, { "type": "pubmed", "citation": "Zhao Y, et al. \"Efficacy and safety of Oral LL-37 against the Omicron BA.5.1.3 variant of SARS-COV-2: A randomized trial.\" J Med Virol, 2023;95(8):e29035. PMID: 37605995.", "pmid": "37605995" }, { "type": "pubmed", "citation": "Yamasaki K, et al. \"Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea.\" Nat Med, 2007;13(8):975-80. PMID: 17676051.", "pmid": "17676051" }, { "type": "pubmed", "citation": "Weber G, et al. \"Human antimicrobial protein hCAP18/LL-37 promotes a metastatic phenotype in breast cancer.\" Breast Cancer Res, 2009;11(1):R6. PMID: 19183447.", "pmid": "19183447" }, { "type": "pubmed", "citation": "Chromek M, et al. \"The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection.\" Nat Med, 2006;12(6):636-41. PMID: 16751768.", "pmid": "16751768" }, { "type": "pubmed", "citation": "Shih CC, et al. \"Antimicrobial peptide cathelicidin LL-37 preserves intestinal barrier and organ function in rats with heat stroke.\" Biomed Pharmacother, 2023;161:114565. PMID: 36958193.", "pmid": "36958193" }, { "type": "pubmed", "citation": "Lee M, et al. \"Human antimicrobial peptide LL-37 induces glial-mediated neuroinflammation.\" Biochem Pharmacol, 2015;94(2):130-41. PMID: 25686659.", "pmid": "25686659" }, { "type": "pubmed", "citation": "Yamshchikov AV, et al. \"Vitamin D status and antimicrobial peptide cathelicidin (LL-37) concentrations in patients with active pulmonary tuberculosis.\" Am J Clin Nutr, 2010;92(3):603-11. PMID: 20610636.", "pmid": "20610636" }, { "type": "pubmed", "citation": "Vandamme D, et al. \"A comprehensive summary of LL-37, the factotum human cathelicidin peptide.\" Cell Immunol, 2012;280(1):22-35. PMID: 23246832.", "pmid": "23246832" } ], "interactionCoverage": "unreviewed", "related": [ "bpc-157", "kpv", "larazotide" ], "lastReviewed": "2026-09-26", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "lonapegsomatropin", "name": "Lonapegsomatropin", "aliases": [ "Skytrofa", "TransCon hGH", "TransCon growth hormone", "ACP-011", "lonapegsomatropin-tcgd" ], "tier": "stub", "category": "growth-hormone", "subcategory": "once-weekly pegylated prodrug growth hormone", "class": "A once-weekly prodrug of recombinant human growth hormone using Ascendis Pharma's TransCon (transient conjugation) platform — native somatropin is reversibly conjugated to a methoxy-PEG carrier via a self-cleaving linker that releases unmodified somatropin into circulation at a controlled rate.", "tagline": "Ascendis Pharma's once-weekly growth hormone prodrug (Skytrofa) — the first weekly GH to receive FDA approval (August 2021) for pediatric GH deficiency in patients aged 1+ years weighing at least 11.5 kg.", "oneLiner": "A once-weekly prodrug of recombinant human somatropin in which native, unmodified hGH is transiently conjugated to a 40 kDa methoxy-PEG carrier through a self-cleaving linker that hydrolyzes at physiologic pH to release unmodified somatropin at a controlled rate over approximately one week. FDA-approved as Skytrofa in August 2021 for pediatric GH deficiency — the first weekly GH formulation approved in the US and notable for releasing bioidentical native somatropin (rather than a modified analog) from the depot.", "sequence": "Native somatropin (191 aa) reversibly conjugated to 40 kDa mPEG via TransCon linker", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": 30, "unit": "hours", "range": "~25–35 hours (apparent, prodrug release-rate-limited)", "notes": "The apparent half-life reflects the controlled prodrug release rate, not the underlying clearance of somatropin. Steady-state in approximately 4 weeks." }, "fdaStatus": "approved", "approvalDetails": "FDA-approved August 2021 as Skytrofa (Ascendis Pharma) for the treatment of pediatric patients one year and older who weigh at least 11.5 kg and have growth failure due to inadequate secretion of endogenous growth hormone. EMA approval January 2022. Ascendis has additional programs exploring adult GHD and other indications.", "mechanism": "Transient conjugation (TransCon) platform: somatropin is covalently linked to a 40 kDa methoxy-PEG carrier via a β-eliminative self-cleaving linker. At physiologic pH and temperature, the linker autohydrolyzes at a predictable rate, releasing native unmodified somatropin into circulation. The released somatropin has the same pharmacology as daily somatotropin but delivered as a continuous low-amplitude infusion rather than a pulsatile pharmacologic dose.", "primaryUses": [ "Pediatric growth hormone deficiency (age 1+, weight ≥11.5 kg)" ], "typicalDose": { "range": "0.24", "unit": "mg/kg/week", "frequency": "once weekly", "route": "subcutaneous", "notes": "Fixed weekly dosing 0.24 mg/kg/week; rotated injection sites. Notable for producing a smoother IGF-1 profile than daily somatropin due to the continuous release kinetics." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Skytrofa (lonapegsomatropin-tcgd) Prescribing Information. Ascendis Pharma." }, { "type": "clinical-trial", "citation": "Thornton PS, et al. \"Weekly Lonapegsomatropin in Treatment-Naïve Children With Growth Hormone Deficiency: The Phase 3 heiGHt Trial.\" J Clin Endocrinol Metab, 2021;106:3184-3195. PMID: 34272849.", "pmid": "34272849" }, { "type": "manufacturer", "citation": "Ascendis Pharma. \"Ascendis Pharma announces FDA approval of Skytrofa.\" Press release, August 25, 2021." } ], "interactionCoverage": "label", "related": [ "somatropin", "somapacitan", "somatrogon", "sermorelin" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.2.3", "named": true, "wording": "lonapegsomatropin", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "A long-acting growth hormone analogue." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.2.3", "named": true, "wording": "lonapegsomatropin", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "A long-acting growth hormone analogue." } ], "moleculeClass": "protein", "moleculeClassBasis": "191 aa" }, { "id": "lutetium-177-dotatate", "name": "Lutetium-177 DOTATATE", "aliases": [ "Lutathera", "177Lu-DOTATATE", "Lutetium Lu 177 dotatate" ], "tier": "stub", "category": "research", "subcategory": "peptide receptor radionuclide therapy", "class": "A radiolabeled somatostatin analog (octreotate conjugated to DOTA chelator and loaded with lutetium-177) used for targeted radiotherapy of somatostatin receptor-positive neuroendocrine tumors.", "tagline": "A targeted radiotherapy peptide — a somatostatin analog armed with a radioactive warhead that delivers lethal radiation directly to neuroendocrine tumor cells expressing sst2 receptors.", "oneLiner": "An octreotide derivative (DOTA-Tyr3-octreotate) chelated with the beta-emitting radionuclide lutetium-177, providing peptide receptor radionuclide therapy (PRRT) by binding somatostatin receptor type 2 on neuroendocrine tumor cells and irradiating them from within.", "sequence": "D-Phe-cyclo[Cys-Tyr-D-Trp-Lys-Thr-Cys]-Thr (DOTA-conjugated at N-terminus)", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": 6.7, "unit": "days", "range": "Physical half-life of ¹⁷⁷Lu: 6.7 days; effective tumor half-life depends on receptor internalization", "notes": "Beta particle range ~2 mm (crossfire effect kills adjacent receptor-negative cells). Also emits low-energy gamma for imaging (theranostic)." }, "fdaStatus": "approved", "approvalDetails": "FDA-approved in 2018 (Lutathera, Novartis/AAA) for somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Landmark NETTER-1 trial showed 79% reduction in risk of progression or death vs. octreotide LAR.", "mechanism": "The DOTATATE peptide binds sst2 with high affinity and is internalized via receptor-mediated endocytosis. Lutetium-177 emits beta particles (Emax 497 keV, range ~2 mm in tissue) that cause DNA double-strand breaks in the tumor cell and nearby cells (crossfire effect). The DOTA chelator stably binds ¹⁷⁷Lu, preventing systemic release. Kidneys and bone marrow are dose-limiting organs.", "primaryUses": [ "Gastroenteropancreatic neuroendocrine tumors (GEP-NETs)", "Midgut carcinoid tumors", "Pheochromocytoma/paraganglioma (investigational)", "sst2-positive tumor research" ], "typicalDose": { "range": "7.4", "unit": "GBq (200 mCi)", "frequency": "every 8 weeks × 4 doses", "route": "intravenous infusion", "notes": "4 doses total. Amino acid infusion (Lys/Arg) co-administered for renal protection. Prior sst2 positivity confirmed by ⁶⁸Ga-DOTATATE PET scan." }, "evidenceLevel": "high", "sources": [ { "type": "clinical-trial", "citation": "Strosberg J, et al. \"Phase 3 trial of ¹⁷⁷Lu-Dotatate for midgut neuroendocrine tumors (NETTER-1).\" N Engl J Med, 2017;376:125-135. PMID: 28076709.", "pmid": "28076709" }, { "type": "fda-pi", "citation": "Lutathera (lutetium Lu 177 dotatate) Prescribing Information. Novartis." } ], "interactionCoverage": "label", "related": [ "octreotide", "lanreotide", "pasireotide" ], "lastReviewed": "2026-04-20", "publishedAt": "2026-04-20", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide-conjugate", "moleculeClassBasis": "radiolabeled somatostatin analog" }, { "id": "lutropin-alfa", "name": "Lutropin alfa", "aliases": [ "Luveris", "rLH" ], "tier": "mid", "category": "sexual-health", "subcategory": "recombinant LH", "class": "Recombinant human luteinizing hormone produced in CHO cells — the only recombinant LH product to reach the US market; approval was withdrawn in 2016 after the sponsor could not complete a required postmarketing study.", "tagline": "Recombinant human LH, given with FSH rather than alone; its largest trial found the endpoints comparable either way.", "oneLiner": "The only recombinant luteinising hormone ever marketed, approved to be added to FSH for follicular development.", "sequence": null, "molecularFormula": null, "molecularWeight": 30000, "halfLife": { "value": null, "unit": null, "range": "10 to 12 hours (terminal)", "source": { "type": "pmid", "pmid": "9496327", "cite": "le Cotonnec JY, et al. \"Clinical pharmacology of recombinant human luteinizing hormone: Part I. Pharmacokinetics after intravenous administration to healthy female volunteers and comparison with urinary human luteinizing hormone.\" Fertil Steril, 1998;69(2):189-94. PMID: 9496327." } }, "fdaStatus": "discontinued", "approvalDetails": "Approved in the US on October 8, 2004 as Luveris (lutropin alfa for injection), NDA 21-322, for use with FSH. FDA withdrew approval of the application at EMD Serono's voluntary request, effective April 12, 2016 (Federal Register 2016-08336), which is why it no longer appears in Drugs@FDA.", "mechanism": "LH/CG receptor (LHCGR) agonism on ovarian theca cells, supporting androgen production that serves as substrate for granulosa-cell aromatization to estradiol during follicle maturation. In LH-deficient hypogonadotropic-hypogonadal women, LH supplementation is required alongside FSH for adequate follicular development and estradiol response.", "primaryUses": [ "Stimulation of follicular development in combination with FSH (former US label)" ], "typicalDose": { "range": "75", "unit": "IU/day", "frequency": "daily", "route": "subcutaneous", "notes": "Historical dose: 75 IU SC daily concomitantly with 75–150 IU Gonal-f SC daily (two separate injections) until follicular development, not to exceed 14 days unless imminent follicular development was evident." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "Humaidan P, et al. \"Efficacy and safety of follitropin alfa/lutropin alfa in ART: a randomized controlled trial in poor ovarian responders.\" Hum Reprod, 2017;32(3):544-555. PMID: 28137754.", "pmid": "28137754" }, { "type": "pubmed", "citation": "Musters AM, et al. \"The effect of recombinant LH on embryo quality: a randomized controlled trial in women with poor ovarian reserve.\" Hum Reprod, 2012;27(1):244-50. PMID: 22095792.", "pmid": "22095792" }, { "type": "pubmed", "citation": "Tarlatzis B, et al. \"The use of recombinant human LH (lutropin alfa) in the late stimulation phase of assisted reproduction cycles: a double-blind, randomized, prospective study.\" Hum Reprod, 2006;21(1):90-4. PMID: 16172149.", "pmid": "16172149" }, { "type": "pubmed", "citation": "Durnerin CI, et al. \"Effects of recombinant LH treatment on folliculogenesis and responsiveness to FSH stimulation.\" Hum Reprod, 2008;23(2):421-6. PMID: 18084048.", "pmid": "18084048" }, { "type": "pubmed", "citation": "le Cotonnec JY, et al. \"Clinical pharmacology of recombinant human luteinizing hormone: Part I. Pharmacokinetics after intravenous administration to healthy female volunteers and comparison with urinary human luteinizing hormone.\" Fertil Steril, 1998;69(2):189-94. PMID: 9496327.", "pmid": "9496327" }, { "type": "other", "citation": "US FDA, Drugs@FDA (openFDA): no application for lutropin alfa or Luveris. Read September 30, 2026." }, { "type": "other", "citation": "US Federal Register 2016-08336, April 12, 2016: FDA withdraws approval of NDA 21-322 for Luveris at EMD Serono's voluntary request, effective that day. Read September 30, 2026." }, { "type": "other", "citation": "US Federal Register E6-9139, June 13, 2006: regulatory review period for Luveris; NDA 21-322 approved October 8, 2004. Read September 30, 2026." } ], "interactionCoverage": "none-found", "related": [ "follitropin-alfa", "menotropin", "hcg", "gonadorelin" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.2.1", "named": true, "wording": "luteinizing hormone (LH)", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "malesOnly": true, "remark": "Lutropin alfa is recombinant human LH." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.2.1", "named": true, "wording": "luteinizing hormone (LH)", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "malesOnly": true, "remark": "Lutropin alfa is recombinant human LH." } ], "moleculeClass": "protein", "moleculeClassBasis": "luteinizing hormone" }, { "id": "macimorelin", "name": "Macimorelin", "aliases": [ "Macrilen", "Ghryvelin", "AEZS-130", "JMV 1843" ], "tier": "stub", "category": "growth-hormone", "subcategory": "oral ghrelin receptor agonist", "class": "Orally active non-peptide ghrelin receptor agonist — FDA-approved as a diagnostic test for adult GH deficiency.", "tagline": "An orally active ghrelin receptor agonist FDA-approved in 2017 as a diagnostic test for adult growth hormone deficiency — the only oral alternative to the insulin tolerance test.", "oneLiner": "A mimetic growth-hormone-secretagogue receptor agonist approved by the FDA as Macrilen for the diagnosis of adult GH deficiency, providing an oral alternative to the insulin tolerance test.", "sequence": null, "molecularFormula": "C26H30N6O3", "molecularWeight": 474.56, "halfLife": { "value": 4, "unit": "hours", "range": "3–5 hours", "notes": "Single-dose diagnostic agent — not for chronic dosing." }, "fdaStatus": "approved", "approvalDetails": "FDA-approved December 2017 as Macrilen (Strongbridge Biopharma, later acquired by Novo Nordisk) for the diagnosis of adult growth hormone deficiency. Drugs@FDA now lists every Macrilen product under NDA 205598 (Aeterna Zentaris) as Discontinued, so the drug remains approved but is no longer marketed in the US (read September 30, 2026).", "mechanism": "Orally active agonist at GHS-R1a. After a single 0.5 mg/kg oral dose, stimulates a robust GH pulse within 30–90 minutes that can be used to distinguish patients with adult GHD from healthy controls, providing a safer diagnostic than the insulin tolerance test (which requires induction of hypoglycemia).", "primaryUses": [ "Diagnosis of adult growth hormone deficiency" ], "typicalDose": { "range": "0.5", "unit": "mg/kg", "frequency": "single diagnostic dose", "route": "oral", "notes": "Prescribing information specifies a specific fasting protocol and serial GH sampling at 30, 45, 60, and 90 minutes post-dose." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Macrilen (macimorelin) Prescribing Information. Novo Nordisk." }, { "type": "clinical-trial", "citation": "Garcia JM, et al. \"Macimorelin as a diagnostic test for adult growth hormone deficiency.\" J Clin Endocrinol Metab, 2018;103:3083-3093. PMID: 29860473.", "pmid": "29860473" } ], "interactionCoverage": "label", "related": [ "mk-677", "sermorelin", "tesamorelin" ], "lastReviewed": "2026-04-18", "publishedAt": "2026-04-18", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.2.4", "named": true, "wording": "macimorelin", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.2.4", "named": true, "wording": "macimorelin", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "small-molecule", "moleculeClassBasis": "non-peptide", "statusVerified": { "date": "2026-09-30", "source": "US FDA, Drugs@FDA (openFDA): Macrilen, Aeterna Zentaris, NDA 205598 — all products Discontinued. Approval stands; marketing has ended." } }, { "id": "magainin", "name": "Magainin", "aliases": [ "Magainin 2", "MSI-78", "Pexiganan" ], "tier": "mid", "category": "immune", "subcategory": "Antimicrobial peptide (AMP)", "class": "Magainin is the antimicrobial peptide from frog skin that launched the modern AMP research field — the foundational discovery by Michael Zasloff in 1987.", "tagline": "The frog-skin peptide that launched antimicrobial peptide research — discovered in 1987 when a researcher noticed surgical frogs never developed infections.", "oneLiner": "A 23-amino-acid cationic amphipathic peptide from the African clawed frog (Xenopus laevis) that kills bacteria by forming pores in their membranes — the foundational discovery that launched the modern AMP field.", "sequence": "GIGKFLHSAKKFGKAFVGEIMNS (Magainin 2)", "molecularFormula": "C114H181N31O29S", "molecularWeight": 2467.9, "halfLife": { "value": null, "unit": null, "range": "not reported in the sources read", "source": { "type": "none", "note": "searched PubMed on October 1, 2026; no human half-life figure in the sources read" } }, "fdaStatus": "research-only", "approvalDetails": "Never approved. Pexiganan, the magainin analogue taken into clinical development as a topical cream for infected diabetic foot ulcers, did not reach approval; no approved product appears in Drugs@FDA (read October 1, 2026).", "mechanism": "Adopts an amphipathic alpha-helical structure on bacterial membranes. The cationic face binds anionic phospholipids. At threshold concentration, forms toroidal pores causing depolarization and lysis. Selective for bacterial over mammalian membranes due to cholesterol and zwitterionic lipid differences.", "primaryUses": [ "Research: foundational model for AMP membrane disruption", "Template for synthetic AMP drug design", "Broad-spectrum antibacterial research" ], "typicalDose": { "range": null, "unit": null, "frequency": null, "route": "topical in its trials", "notes": "Never approved. Pexiganan was tested as a topical cream for mildly infected diabetic foot ulcers; the laboratory work reports an all-organism MIC90 of 32 mcg/mL, more than 250-fold below the cream's concentration." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Lipsky BA, et al. \"Topical versus systemic antimicrobial therapy for treating mildly infected diabetic foot ulcers: a randomized, controlled, double-blinded, multicenter trial of pexiganan cream.\" Clin Infect Dis, 2008;47(12):1537-45. PMID: 18990064.", "pmid": "18990064" }, { "type": "pubmed", "citation": "Flamm RK, et al. \"In vitro spectrum of pexiganan activity when tested against pathogens from diabetic foot infections and with selected resistance mechanisms.\" Antimicrob Agents Chemother, 2015;59(3):1751-4. PMID: 25583717.", "pmid": "25583717" }, { "type": "pubmed", "citation": "Flamm RK, et al. \"In vitro spectrum of pexiganan activity; bactericidal action and resistance selection tested against pathogens with elevated MIC values to topical agents.\" Diagn Microbiol Infect Dis, 2016;86(1):66-9. PMID: 27352729.", "pmid": "27352729" }, { "type": "pubmed", "citation": "Fuchs PC, et al. \"In vitro antimicrobial activity of MSI-78, a magainin analog.\" Antimicrob Agents Chemother, 1998;42(5):1213-6. PMID: 9593152.", "pmid": "9593152" }, { "type": "pubmed", "citation": "Ge Y, et al. \"In vitro susceptibility to pexiganan of bacteria isolated from infected diabetic foot ulcers.\" Diagn Microbiol Infect Dis, 1999;35(1):45-53. PMID: 10529881.", "pmid": "10529881" }, { "type": "pubmed", "citation": "Zasloff M. \"Magainins, a class of antimicrobial peptides from Xenopus skin: isolation, characterization of two active forms, and partial cDNA sequence of a precursor.\" Proc Natl Acad Sci U S A, 1987;84(15):5449-53. PMID: 3299384.", "pmid": "3299384" }, { "type": "pubmed", "citation": "Zasloff M. \"Antimicrobial peptides of multicellular organisms.\" Nature, 2002;415(6870):389-95. PMID: 11807545.", "pmid": "11807545" } ], "interactionCoverage": "unreviewed", "related": [ "pexiganan", "ll-37", "cecropin", "melittin", "cathelicidin" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-21", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "maridebart-cafraglutide", "name": "Maridebart cafraglutide", "aliases": [ "MariTide", "AMG 133", "AMG-133" ], "tier": "stub", "category": "pipeline", "subcategory": "GIPR antagonist + GLP-1R agonist conjugate", "class": "A peptide-antibody conjugate combining a GIP receptor antagonist monoclonal antibody with two GLP-1 receptor agonist peptides.", "tagline": "Amgen's once-monthly obesity injection — Phase 3 MARITIME program underway, ~20% weight loss at 52 weeks in Phase 2 (NEJM 2025), approximately 21-day half-life enabling monthly or less frequent dosing.", "oneLiner": "A first-in-class peptide-antibody conjugate developed by Amgen, consisting of a monoclonal antibody antagonist of the GIP receptor conjugated via amino-acid linkers to two GLP-1 receptor agonist peptides, delivering combined GIPR blockade and GLP-1R activation with a ~21-day plasma half-life — roughly triple that of any approved once-weekly incretin.", "sequence": null, "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": 21, "unit": "days", "range": "~21 days", "notes": "Antibody-driven half-life supports once-monthly or even less frequent dosing; Phase 2 tested monthly and quarterly regimens." }, "fdaStatus": "clinical-trials", "approvalDetails": "Not approved. Amgen developer. Phase 3 MARITIME program is ongoing (MARITIME-1 in obesity/overweight, MARITIME-2 in type 2 diabetes) with additional Phase 3 trials in atherosclerotic cardiovascular disease, heart failure, and obstructive sleep apnea. Phase 2 results published in NEJM (Jastreboff et al., 2025; N=592) showed mean weight loss of up to 20% at 52 weeks without a weight-loss plateau. Initial Phase 3 readouts anticipated around 2027.", "mechanism": "Unusually, maridebart cafraglutide is a GIP receptor antagonist combined with a GLP-1 receptor agonist — the opposite GIP directionality of tirzepatide (which is a GIPR agonist + GLP-1R agonist). Preclinical evidence suggests chronic GIPR blockade may improve insulin sensitivity and enhance weight loss when combined with GLP-1R agonism, though the precise biology of \"GIPR agonism vs antagonism in obesity\" remains one of the more contested questions in incretin pharmacology.", "primaryUses": [ "Obesity (Phase 3 investigational)", "Type 2 diabetes (Phase 3 investigational)", "Cardiovascular, renal, and sleep apnea indications in earlier development" ], "typicalDose": { "range": "140–420", "unit": "mg", "frequency": "monthly or every 8 weeks (investigational)", "route": "subcutaneous", "notes": "Phase 2 tested 140, 280, and 420 mg every 4 weeks, and 420 mg every 8 weeks. Dose-escalation schedules are being optimized in Phase 3 to manage GI tolerability." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "Jastreboff AM, et al. \"Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity — A Phase 2 Trial.\" N Engl J Med, 2025;393:2275. PMID: 40549887.", "pmid": "40549887" }, { "type": "news-release", "citation": "Amgen. \"Amgen Announces Robust Weight Loss With MariTide in People Living With Obesity or Overweight at 52 Weeks in a Phase 2 Study.\" November 26, 2024." }, { "type": "clinicaltrials", "citation": "NCT06858878 — Phase 3 MARITIME-2 trial in adults with type 2 diabetes and obesity/overweight. ClinicalTrials.gov." } ], "interactionCoverage": "partial", "related": [ "tirzepatide", "retatrutide", "semaglutide", "cagrisema" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." } ], "moleculeClass": "peptide-conjugate", "moleculeClassBasis": "peptide-antibody conjugate" }, { "id": "matrixyl", "name": "Matrixyl", "aliases": [ "Palmitoyl Pentapeptide-4", "Palmitoyl Pentapeptide-3", "Pal-KTTKS", "Matrixyl 3000" ], "tier": "mid", "category": "cosmetic", "subcategory": "topical collagen-stimulating peptide", "class": "A lipopeptide consisting of the matrikine KTTKS (collagen I–derived fragment) conjugated to palmitic acid for skin penetration.", "tagline": "The palmitoyl pentapeptide in anti-wrinkle creams: a cosmetic ingredient, not a drug, with two small randomised trials in people.", "oneLiner": "Palmitoyl pentapeptide-4, a collagen fragment with a fatty acid attached so it can penetrate skin, sold under the trade name Matrixyl.", "sequence": "Pal-Lys-Thr-Thr-Lys-Ser", "molecularFormula": "C39H75N7O9", "molecularWeight": 802.07, "halfLife": { "value": null, "unit": null, "range": "topical only", "notes": "Systemic absorption minimal; local skin penetration via palmitoyl conjugation.", "source": { "type": "qualitative", "note": "a description with no figure; no half-life measurement is cited for it" } }, "fdaStatus": "research-only", "approvalDetails": "A cosmetic ingredient, not a drug. Cosmetics do not require FDA approval before sale, and palmitoyl pentapeptide-4 has no drug approval anywhere.", "mechanism": "The KTTKS fragment is a natural signal produced by collagen-I degradation; fibroblasts respond to KTTKS as a feedback signal by upregulating collagen and glycosaminoglycan synthesis. Palmitoylation enables skin penetration of the otherwise hydrophilic peptide. Clinical studies show modest improvements in skin roughness and fine-line depth over 12 weeks of twice-daily application.", "primaryUses": [ "Anti-wrinkle cosmetic ingredient (topical)" ], "typicalDose": { "range": "3–5", "unit": "% (topical formulation)", "frequency": "twice daily", "route": "topical", "notes": "Cosmetic concentrations." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "Robinson LR, et al. \"Topical palmitoyl pentapeptide provides improvement in photoaged human facial skin.\" Int J Cosmet Sci, 2005;27(3):155-60. PMID: 18492182.", "pmid": "18492182" }, { "type": "pubmed", "citation": "Aruan RR, et al. \"Double-blind, Randomized Trial on the Effectiveness of Acetylhexapeptide-3 Cream and Palmitoyl Pentapeptide-4 Cream for Crow's Feet.\" J Clin Aesthet Dermatol, 2023;16(2):37-43. PMID: 36909866.", "pmid": "36909866" }, { "type": "pubmed", "citation": "Kachooeian M, et al. \"Matrixyl Patch vs Matrixyl Cream: A Comparative In Vivo Investigation of Matrixyl (MTI) Effect on Wound Healing.\" ACS Omega, 2022;7(28):24695-24704. PMID: 35874243.", "pmid": "35874243" }, { "type": "pubmed", "citation": "Choi YL, et al. \"Dermal Stability and In Vitro Skin Permeation of Collagen Pentapeptides (KTTKS and palmitoyl-KTTKS).\" Biomol Ther (Seoul), 2014;22(4):321-7. PMID: 25143811.", "pmid": "25143811" }, { "type": "pubmed", "citation": "Katayama K, et al. \"A pentapeptide from type I procollagen promotes extracellular matrix production.\" J Biol Chem, 1993;268(14):9941-4. PMID: 8486721.", "pmid": "8486721" } ], "interactionCoverage": "unreviewed", "related": [ "argireline", "snap-8", "ghk-cu" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." } ], "moleculeClass": "peptide" }, { "id": "mazdutide", "name": "Mazdutide", "aliases": [ "IBI362", "LY3305677", "OXM-3" ], "tier": "mid", "category": "metabolic", "subcategory": "GLP-1/glucagon dual agonist", "class": "Oxyntomodulin-based GLP-1/glucagon dual agonist, approved in China in 2025.", "tagline": "The first dual glucagon and GLP-1 agonist approved for weight loss anywhere, by China in June 2025; not approved in the US.", "oneLiner": "A once-weekly peptide that activates both the GLP-1 and glucagon receptors, licensed from Eli Lilly to Innovent for China.", "sequence": null, "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": null, "range": "not reported in the sources read; dosed once weekly", "source": { "type": "none", "note": "searched PubMed on September 30, 2026; no half-life reported" } }, "fdaStatus": "not-approved-us", "approvalDetails": "Approved by China's NMPA on June 27, 2025 for chronic weight management in adults with overweight or obesity, mainly on GLORY-1 (Innovent Biologics, licensed from Eli Lilly). Not approved in the US; Lilly holds rights outside China.", "mechanism": "Oxyntomodulin-based dual agonism at GLP-1 and glucagon receptors. GLP-1 drives appetite suppression and glycemic control; glucagon contributes to energy expenditure and hepatic fat reduction. GLORY-1 Phase 3 trial in Chinese obese adults showed ~14.4% weight loss at 48 weeks with 9 mg weekly dosing.", "primaryUses": [ "Chronic weight management (approved in China)", "Type 2 diabetes (trials)" ], "typicalDose": { "range": "3–9", "unit": "mg", "frequency": "weekly", "route": "subcutaneous", "notes": "GLORY-1 trial titrated to 6 mg or 9 mg weekly. China labeling reflects Phase 3 regimen." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Ji L, et al. \"Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight.\" N Engl J Med, 2025;392(22):2215-2225. PMID: 40421736.", "pmid": "40421736" }, { "type": "pubmed", "citation": "Ji L, et al. \"A phase 2 randomised controlled trial of mazdutide in Chinese overweight adults or adults with obesity.\" Nat Commun, 2023;14(1):8289. PMID: 38092790.", "pmid": "38092790" }, { "type": "pubmed", "citation": "Zhang B, et al. \"Efficacy and Safety of Mazdutide in Chinese Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial.\" Diabetes Care, 2024;47(1):160-168. PMID: 37943529.", "pmid": "37943529" }, { "type": "pubmed", "citation": "Guo L, et al. \"Mazdutide versus dulaglutide in Chinese adults with type 2 diabetes.\" Nature, 2026;652(8108):181-188. PMID: 41407860.", "pmid": "41407860" }, { "type": "other", "citation": "Innovent Biologics, announcement of NMPA approval of mazdutide for chronic weight management in Chinese adults with overweight or obesity, June 30, 2025; read September 30, 2026." }, { "type": "clinicaltrials", "citation": "ClinicalTrials.gov NCT05607680: GLORY-1, IBI362 (mazdutide) in participants with obesity or overweight (registry record and the trial's NEJM report, read September 30, 2026)." } ], "interactionCoverage": "none-found", "related": [ "survodutide", "retatrutide", "semaglutide" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": "China (NMPA)", "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "mecasermin", "name": "Mecasermin", "aliases": [ "Increlex", "rhIGF-1", "recombinant IGF-1", "somatomedin C" ], "tier": "mid", "category": "growth-hormone", "subcategory": "recombinant human IGF-1", "class": "Recombinant human insulin-like growth factor 1 (rhIGF-1), structurally identical to endogenous IGF-1 (70 amino acids, three disulfide bonds).", "tagline": "Ipsen's recombinant human IGF-1 (Increlex) — FDA-approved in 2005 for severe primary IGF-1 deficiency; the direct replacement for IGF-1 in patients whose own IGF-1 production is inadequate despite normal GH levels.", "oneLiner": "Recombinant human insulin-like growth factor 1 (rhIGF-1), a 70-amino-acid single-chain peptide identical in sequence to endogenous IGF-1, produced in E. coli. FDA-approved as Increlex in August 2005 for the long-term treatment of growth failure in children with severe primary IGF-1 deficiency (Laron syndrome, GH receptor defects, post-GH antibody states) or with GH gene deletion who have developed neutralizing antibodies to GH. Provides IGF-1 replacement when the patient cannot generate it from exogenous GH. Acquired by Ipsen from Tercica; marketed as Increlex in most countries.", "sequence": "GPETLCGAELVDALQFVCGDRGFYFNKPTGYGSSSRRAPQTGIVDECCFRSCDLRRLEMYCAPLKPAKSA", "molecularFormula": "C331H512N94O101S7", "molecularWeight": 7649, "halfLife": { "value": null, "unit": null, "range": "the label gives no half-life; it reports bioavailability close to 100% after subcutaneous dosing in healthy subjects, and that over 80% of circulating IGF-1 is bound in a complex with IGFBP-3", "source": { "type": "label", "ref": "Increlex (mecasermin) prescribing information, sections 1, 2 and 12.3 (DailyMed SPL version 5, effective May 18, 2026; read October 1, 2026)" } }, "fdaStatus": "approved", "approvalDetails": "Increlex, BLA 021839, approved August 30, 2005, for growth failure in children two years and older with severe primary IGF-1 deficiency or growth hormone gene deletion with neutralising antibodies to growth hormone. The label states it is not a substitute for growth hormone in growth hormone's own indications (Drugs@FDA and the label, read October 1, 2026).", "mechanism": "Binds the IGF-1 receptor (IGF-1R), a tyrosine kinase receptor structurally related to the insulin receptor, triggering autophosphorylation and activation of PI3K/Akt and Ras/MAPK signaling to drive anabolic growth effects on bone (longitudinal growth via chondrocyte proliferation), muscle, and other tissues. Also activates the IGF-1R / insulin receptor hybrid receptor and, at high concentrations, the insulin receptor itself — which is the basis for the hypoglycemia risk that is the primary safety concern in dosing.", "primaryUses": [ "Severe primary IGF-1 deficiency in children", "GH gene deletion with neutralizing antibodies to GH" ], "typicalDose": { "range": "0.04-0.12", "unit": "mg/kg", "frequency": "twice daily", "route": "subcutaneous", "notes": "Increlex label: start at 0.04 to 0.08 mg/kg twice daily; if tolerated for at least a week the dose may rise by 0.04 mg/kg per dose to a maximum of 0.12 mg/kg twice daily. Rotate injection sites. Supervision by a physician experienced in these disorders." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Increlex (mecasermin) prescribing information, sections 1, 2 and 12.3 (DailyMed SPL version 5, effective May 18, 2026; read October 1, 2026)." }, { "type": "pubmed", "citation": "Ramon-Krauel M, et al. \"Near-Adult Height Outcomes in Patients Treated With rhIGF-1 for Severe Growth Failure: Real-World IGFD Registry Data.\" J Clin Endocrinol Metab, 2026;111(2):e500-e511. PMID: 40626687.", "pmid": "40626687" }, { "type": "pubmed", "citation": "Bang P, et al. \"Frequency and Predictive Factors of Hypoglycemia in Patients Treated With rhIGF-1: Data From the Eu-IGFD Registry.\" J Clin Endocrinol Metab, 2023;109(1):46-56. PMID: 37579214.", "pmid": "37579214" }, { "type": "pubmed", "citation": "Bang P, et al. \"Effectiveness and safety of rhIGF1 therapy in patients with or without Laron syndrome.\" Eur J Endocrinol, 2021;184(2):267-276. PMID: 33434161.", "pmid": "33434161" }, { "type": "pubmed", "citation": "Ley D, et al. \"rhIGF-1/rhIGFBP-3 in Preterm Infants: A Phase 2 Randomized Controlled Trial.\" J Pediatr, 2019;206:56-65.e8. PMID: 30471715.", "pmid": "30471715" }, { "type": "pubmed", "citation": "Ribeiro FCP, et al. \"Mecasermin for the treatment of Rett Syndrome: a systematic review.\" Neurogenetics, 2025;26(1):78. PMID: 41174329.", "pmid": "41174329" }, { "type": "pubmed", "citation": "Chernausek SD, et al. \"Long-term treatment with recombinant insulin-like growth factor (IGF)-I in children with severe IGF-I deficiency due to growth hormone insensitivity.\" J Clin Endocrinol Metab, 2007;92(3):902-10. PMID: 17192294.", "pmid": "17192294" }, { "type": "pubmed", "citation": "Backeljauw PF, et al. \"Therapy for 6 years with recombinant human insulin-like growth factor-I in children with severe primary IGF-I deficiency.\" J Clin Endocrinol Metab." } ], "interactionCoverage": "partial", "related": [ "somatropin", "mecasermin-rinfabate", "igf-1-lr3", "igf-1-des" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.3", "named": true, "wording": "IGF-1, mecasermin", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.3", "named": true, "wording": "IGF-1, mecasermin", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "mecasermin-rinfabate", "name": "Mecasermin rinfabate", "aliases": [ "iPlex", "rhIGF-1/rhIGFBP-3", "IGF-1/IGFBP-3 complex" ], "tier": "mid", "category": "growth-hormone", "subcategory": "discontinued IGF-1 / IGFBP-3 binary complex", "class": "A recombinant binary complex of human IGF-1 and its principal binding protein IGFBP-3, developed to provide IGF-1 replacement with a longer half-life and lower hypoglycemia risk than rhIGF-1 alone.", "tagline": "IGF-1 delivered bound to its carrier protein: approved in 2005 as iPlex, now listed as discontinued in the US.", "oneLiner": "An equimolar complex of recombinant IGF-1 and IGFBP-3, designed to act longer and cause less hypoglycaemia than free IGF-1.", "sequence": "Recombinant human IGF-1 (70 aa) in binary complex with recombinant human IGFBP-3 (264 aa)", "molecularFormula": null, "molecularWeight": 36000, "halfLife": { "value": 21, "unit": "hours", "range": "about 21 hours for IGF-I after the complex (four adults)", "source": { "type": "pmid", "pmid": "16403822", "cite": "Camacho-Hübner C, et al. \"Pharmacokinetic studies of recombinant human insulin-like growth factor I (rhIGF-I)/rhIGF-binding protein-3 complex administered to patients with growth hormone insensitivity syndrome.\" J Clin Endocrinol Metab, 2006;91(4):1246-53. PMID: 16403822." } }, "fdaStatus": "discontinued", "approvalDetails": "FDA-approved as iPlex (Insmed, BLA 021884) for severe primary IGF deficiency and growth hormone gene deletion with neutralising antibodies. Drugs@FDA now lists iPlex as Discontinued, so the drug remains approved but is no longer marketed in the US (read September 30, 2026).", "mechanism": "Same IGF-1R agonism as free rhIGF-1, but delivered as a preformed IGF-1 / IGFBP-3 binary complex. The complex slows renal clearance, buffers the acute post-dose insulin-receptor-mediated hypoglycemia effect, and resembles the physiological circulating form of IGF-1 (which is almost entirely bound to IGFBP-3 and acid-labile subunit in a ternary complex).", "primaryUses": [ "Severe primary IGF-1 deficiency (former US indication)", "Retinopathy of prematurity prevention (phase 2)" ], "typicalDose": { "range": "0.5–2.0", "unit": "mg/kg/day", "frequency": "once or twice daily", "route": "subcutaneous", "notes": "Historical dosing; not currently available for clinical use." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "Hansen-Pupp I, et al. \"Continuous longitudinal infusion of rhIGF-1/rhIGFBP-3 in extremely preterm infants: Evaluation of feasibility in a phase II study.\" Growth Horm IGF Res, 2017;36:44-51. PMID: 28934640.", "pmid": "28934640" }, { "type": "pubmed", "citation": "Kemp SF. \"Mecasermin rinfabate.\" Drugs Today (Barc), 2007;43(3):149-55. PMID: 17380212.", "pmid": "17380212" }, { "type": "pubmed", "citation": "Williams RM, et al. \"Mecasermin rinfabate: rhIGF-I/rhIGFBP-3 complex: iPLEX.\" Expert Opin Drug Metab Toxicol, 2008;4(3):311-24. PMID: 18363546.", "pmid": "18363546" }, { "type": "pubmed", "citation": "Camacho-Hübner C, et al. \"Pharmacokinetic studies of recombinant human insulin-like growth factor I (rhIGF-I)/rhIGF-binding protein-3 complex administered to patients with growth hormone insensitivity syndrome.\" J Clin Endocrinol Metab, 2006;91(4):1246-53. PMID: 16403822.", "pmid": "16403822" }, { "type": "other", "citation": "US FDA, Drugs@FDA (openFDA): IPLEX (mecasermin rinfabate), Insmed, BLA 021884, Discontinued. Read September 30, 2026." } ], "interactionCoverage": "studied", "related": [ "mecasermin", "somatropin", "igf-1-lr3" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.3", "named": false, "wording": "IGF-1, mecasermin", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "A complex of mecasermin, which the List names, with its binding protein IGFBP-3." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.3", "named": false, "wording": "IGF-1, mecasermin", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "A complex of mecasermin, which the List names, with its binding protein IGFBP-3." } ], "moleculeClass": "protein", "moleculeClassBasis": "binary complex" }, { "id": "melanotan-ii", "name": "Melanotan II", "aliases": [ "MT-II", "MT2", "melanotan 2", "MT-2", "Barbie drug" ], "tier": "full", "category": "sexual-health", "subcategory": "melanocortin agonist", "class": "A non-selective cyclic heptapeptide agonist at melanocortin receptors (MC1R, MC3R, MC4R, MC5R).", "tagline": "An unapproved melanocortin agonist sold as a tanning and libido injection, with small 1990s trials and case reports of changing moles, melanoma, priapism and kidney injury.", "oneLiner": "A cyclic heptapeptide non-selective melanocortin agonist developed at the University of Arizona in the 1990s, now sold as an unregulated research chemical for tanning and sexual effects despite repeated case reports of melanocytic changes, eruptive nevi, and melanoma in situ.", "sequence": "Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2", "molecularFormula": "C50H69N15O9", "molecularWeight": 1024.18, "halfLife": { "value": null, "unit": null, "range": "not measured in humans", "notes": "In rats given an intravenous dose, plasma levels fell in two phases (Ugwu 1994). No human half-life appears in the abstracts we hold; the '~1 hour' given here before had no source." }, "fdaStatus": "research-only", "approvalDetails": "Not approved by any regulatory body. Development discontinued by Palatin Technologies in 2000 in favor of its metabolite PT-141 (bremelanotide). Sold only through research-chemical and unregulated online channels. Health authorities in Australia, the UK, and the US have issued public warnings.", "mechanism": "Non-selective agonist at MC1R (melanocyte stimulation → melanin production and tanning), MC3R and MC4R (central — appetite suppression and sexual arousal via hypothalamic pathways), and MC5R (sebaceous gland stimulation). The central MC4R agonism underlies both the increased libido/spontaneous erections reported by users and the adverse effects (nausea, yawning, flushing). MC1R agonism drives eumelanin synthesis but also stimulates melanocyte proliferation — the likely mechanism behind the mole changes and atypical nevi reported in case series.", "primaryUses": [ "Unregulated tanning (off-label community use)", "Unregulated sexual function enhancement (off-label community use)", "Historical tanning research" ], "typicalDose": { "range": "0.25–1", "unit": "mg", "frequency": "daily loading, then 2–3× weekly", "route": "subcutaneous", "notes": "Community dosing only. NOT MEDICAL GUIDANCE. Multiple case reports of melanocytic changes, dysplastic nevi, and melanoma in situ associated with use — including at least one case from a regulated compounding pharmacy." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Dorr RT, et al. \"Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study.\" Life Sci, 1996;58(20):1777-84. PMID: 8637402.", "pmid": "8637402" }, { "type": "pubmed", "citation": "Wessells H, et al. \"Melanocortin receptor agonists, penile erection, and sexual motivation: human studies with Melanotan II.\" Int J Impot Res, 2000;12 Suppl 4:S74-9. PMID: 11035391.", "pmid": "11035391" }, { "type": "pubmed", "citation": "Gilhooley E, et al. \"Melanotan II User Experience: A Qualitative Study of Online Discussion Forums.\" Dermatology, 2021;237(6):995-999. PMID: 34464955.", "pmid": "34464955" }, { "type": "pubmed", "citation": "Breindahl T, et al. \"Identification and characterization by LC-UV-MS/MS of melanotan II skin-tanning products sold illegally on the Internet.\" Drug Test Anal, 2015;7(2):164-72. PMID: 24771717.", "pmid": "24771717" }, { "type": "review", "citation": "Peters B, et al. \"Melanotan II: a possible cause of renal infarction: review of the literature and case report.\" CEN Case Rep, 2020;9(2):159-161. PMID: 31953620.", "pmid": "31953620" }, { "type": "pubmed", "citation": "Giuliano F, et al. \"The use of telemetry technology to test the proerectile effect of melanotan-II (MT-II) in conscious rats.\" Eur Urol, 2005;48(1):145-51; discussion 151-2. PMID: 15967265.", "pmid": "15967265" }, { "type": "pubmed", "citation": "Raposinho PD, et al. \"The melanocortin agonist Melanotan-II reduces the orexigenic and adipogenic effects of neuropeptide Y (NPY) but does not affect the NPY-driven suppressive effects on the gonadotropic and somatotropic axes in the male rat.\" J Neuroendocrinol, 2003;15(2):173-81. PMID: 12535159.", "pmid": "12535159" }, { "type": "pubmed", "citation": "Banno R, et al. \"The melanocortin agonist melanotan II increases insulin sensitivity in OLETF rats.\" Peptides, 2004;25(8):1279-86. PMID: 15350695.", "pmid": "15350695" }, { "type": "pubmed", "citation": "Strader AD, et al. \"The effects of the melanocortin agonist (MT-II) on subcutaneous and visceral adipose tissue in rodents.\" J Pharmacol Exp Ther, 2007;322(3):1153-61. PMID: 17567964.", "pmid": "17567964" }, { "type": "pubmed", "citation": "Eliason NL, et al. \"Melanocortin receptor agonist melanotan-II microinjected in the nucleus accumbens decreases appetitive and consumptive responding for food.\" Neuropeptides, 2022;96:102289. PMID: 36155088.", "pmid": "36155088" }, { "type": "pubmed", "citation": "Wolters FL, et al. \"Co-treatment with melanotan-II, a potent melanocortin, does not protect against cisplatin ototoxicity.\" Hear Res, 2002;172(1-2):110-7. PMID: 12361873.", "pmid": "12361873" }, { "type": "pubmed", "citation": "McMillan TR, et al. \"Melanotan II, a melanocortin agonist, partially rescues the impaired thermogenic capacity of pituitary adenylate cyclase-activating polypeptide deficient mice.\" Exp Physiol, 2021;106(2):427-437. PMID: 33332767.", "pmid": "33332767" }, { "type": "pubmed", "citation": "Wekwejt P, et al. \"Melanotan-II reverses memory impairment induced by a short-term HF diet.\" Biomed Pharmacother, 2023;165:115129. PMID: 37478579.", "pmid": "37478579" }, { "type": "pubmed", "citation": "Tomassi S, et al. \"CLIPSing Melanotan-II to Discover Multiple Functionally Selective hMCR Agonists.\" J Med Chem, 2022;65(5):4007-4017. PMID: 35188390.", "pmid": "35188390" }, { "type": "pubmed", "citation": "Wessells H, et al. \"Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: double-blind, placebo controlled crossover study.\" J Urol, 1998;160(2):389-93. PMID: 9679884.", "pmid": "9679884" }, { "type": "pubmed", "citation": "Wessells H, et al. \"Effect of an alpha-melanocyte stimulating hormone analog on penile erection and sexual desire in men with organic erectile dysfunction.\" Urology, 2000;56(4):641-6. PMID: 11018622.", "pmid": "11018622" }, { "type": "review", "citation": "Habbema L, et al. \"Risks of unregulated use of alpha-melanocyte-stimulating hormone analogues: a review.\" Int J Dermatol, 2017;56:975-980. PMID: 28266027.", "pmid": "28266027" }, { "type": "pubmed", "citation": "Paurobally D, et al. \"Melanotan-associated melanoma.\" Br J Dermatol, 2011;164:1403-1405. PMID: 21564053.", "pmid": "21564053" }, { "type": "pubmed", "citation": "Devlin J, et al. \"Melanotan II overdose associated with priapism.\" Clin Toxicol (Phila), 2013;51(4):383. PMID: 23537392.", "pmid": "23537392" }, { "type": "pubmed", "citation": "Langan EA, et al. \"Melanotropic peptides: more than just 'Barbie drugs' and 'sun-tan jabs'?.\" Br J Dermatol, 2010;163(3):451-5. PMID: 20545686.", "pmid": "20545686" } ], "interactionCoverage": "unreviewed", "related": [ "pt-141", "afamelanotide" ], "lastReviewed": "2026-09-26", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "melatonin", "name": "Melatonin", "aliases": [ "N-acetyl-5-methoxytryptamine", "5-methoxy-N-acetyltryptamine", "Circadin", "MT" ], "tier": "mid", "category": "longevity", "subcategory": "pineal indoleamine hormone", "class": "Note: Melatonin is an indoleamine hormone synthesized from tryptophan (via serotonin), not a peptide. It is included here because it is ubiquitously stacked with peptide therapeutics in sleep, longevity, and circadian-health protocols.", "tagline": "The pineal darkness signal: an unregulated supplement in the US, a prescription prolonged-release medicine for insomnia in Europe.", "oneLiner": "A hormone released at night that times the circadian system rather than sedating, best evidenced where the body's own output has fallen.", "sequence": "Not applicable — Melatonin is an indoleamine (N-acetyl-5-methoxytryptamine) synthesized from tryptophan via serotonin, not a peptide.", "molecularFormula": "C13H16N2O2", "molecularWeight": 232.28, "halfLife": { "value": null, "unit": null, "range": "about 1 hour; 1.6 hours extended-release", "source": { "type": "pmid", "pmid": "37150895", "cite": "Mun JG, et al. \"A Randomized, Double-Blind, Crossover Study to Investigate the Pharmacokinetics of Extended-Release Melatonin Compared to Immediate-Release Melatonin in Healthy Adults.\" J Diet Suppl, 2024;21(2):182-194. PMID: 37150895." } }, "fdaStatus": "supplement", "approvalDetails": "Sold over the counter as a dietary supplement in the US, outside drug regulation, with no requirement that contents match the label. In the EU and UK, prolonged-release melatonin is a prescription medicine for primary insomnia in patients aged 55 and over.", "mechanism": "Synthesized from serotonin via N-acetyltransferase and HIOMT in the pineal gland, with secretion entrained by the suprachiasmatic nucleus under light-dark cycle control. Activates two high-affinity G-protein-coupled receptors — MT1 (primarily involved in REM sleep regulation and acute sleep onset) and MT2 (NREM sleep and circadian phase-shifting). Also has direct free-radical scavenging and antioxidant properties, and modulates mitochondrial function; these non-receptor effects are the basis for much of the longevity-interest research. Supraphysiological doses (common in OTC products) saturate receptors and may produce paradoxical or diminishing effects.", "primaryUses": [ "Primary insomnia in people aged 55 and over (EU/UK prescription indication)", "Sleep onset problems, including in children (trial evidence)" ], "typicalDose": { "range": "0.3–10", "unit": "mg", "frequency": "30–60 minutes before bedtime", "route": "oral (most common); sublingual, transdermal, or injectable (less common)", "notes": "Physiological doses (0.3–1 mg) are often as effective as higher OTC doses (3–10 mg) for sleep onset. Injectable compounded melatonin is uncommon but included in some wellness IV protocols. US OTC products frequently exceed labeled content by wide margins." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "Wade AG, et al. \"Efficacy of prolonged release melatonin in insomnia patients aged 55-80 years: quality of sleep and next-day alertness outcomes.\" Curr Med Res Opin, 2007;23(10):2597-605. PMID: 17875243.", "pmid": "17875243" }, { "type": "pubmed", "citation": "Wade AG, et al. \"Nightly treatment of primary insomnia with prolonged release melatonin for 6 months: a randomized placebo controlled trial on age and endogenous melatonin as predictors of efficacy and safety.\" BMC Med, 2010;8:51. PMID: 20712869.", "pmid": "20712869" }, { "type": "pubmed", "citation": "Jalilolghadr S, et al. \"The effect of treatment with melatonin on primary school aged children with difficulty in initiation and maintenance of sleep.\" Turk J Pediatr, 2022;64(6):993-1000. PMID: 36583881.", "pmid": "36583881" }, { "type": "pubmed", "citation": "Lemoine P, et al. \"Prolonged-release melatonin improves sleep quality and morning alertness in insomnia patients aged 55 years and older and has no withdrawal effects.\" J Sleep Res, 2007;16(4):372-80. PMID: 18036082.", "pmid": "18036082" }, { "type": "pubmed", "citation": "Liu J, et al. \"MT1 and MT2 Melatonin Receptors: A Therapeutic Perspective.\" Annu Rev Pharmacol Toxicol, 2016;56:361-83. PMID: 26514204.", "pmid": "26514204" }, { "type": "pubmed", "citation": "Comai S, et al. \"Melatonin, Melatonin Receptors and Sleep: Moving Beyond Traditional Views.\" J Pineal Res, 2024;76(7):e13011. PMID: 39400423.", "pmid": "39400423" }, { "type": "pubmed", "citation": "Mun JG, et al. \"A Randomized, Double-Blind, Crossover Study to Investigate the Pharmacokinetics of Extended-Release Melatonin Compared to Immediate-Release Melatonin in Healthy Adults.\" J Diet Suppl, 2024;21(2):182-194. PMID: 37150895.", "pmid": "37150895" } ], "interactionCoverage": "partial", "related": [ "dsip", "epithalon", "oxytocin" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-20", "fdaApproved": false, "approvedElsewhere": "EU and UK (Circadin — prolonged-release, prescription-only)", "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Also sold as a dietary supplement in the US." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Also sold as a dietary supplement in the US." } ], "moleculeClass": "small-molecule", "moleculeClassBasis": "indoleamine" }, { "id": "melittin", "name": "Melittin", "aliases": [ "Bee venom peptide", "Apis mellifera peptide" ], "tier": "stub", "category": "immune", "subcategory": "Venom-derived antimicrobial/cytolytic peptide", "class": "Melittin is the primary active component of bee venom — a potent membrane-disrupting peptide being researched for antimicrobial, anticancer, and anti-inflammatory applications.", "tagline": "The main weapon in bee venom — a powerful membrane-disrupting peptide being repurposed as an antimicrobial and anticancer research tool.", "oneLiner": "A 26-amino-acid amphipathic alpha-helical peptide comprising ~50% of honeybee venom dry weight that forms pores in lipid bilayers, producing potent cytolytic, antimicrobial, and anticancer activity.", "sequence": "GIGAVLKVLTTGLPALISWIKRKRQQ-amide", "molecularFormula": "C131H229N39O31", "molecularWeight": 2846.5, "halfLife": { "value": null, "unit": null, "range": "Minutes in serum", "notes": "Rapidly degraded. Research focuses on nanoparticle-encapsulated melittin for targeted delivery." }, "fdaStatus": "research-only", "approvalDetails": "Not approved. In preclinical development for targeted anticancer therapy (melittin-loaded nanoparticles).", "mechanism": "Forms toroidal pores (~2.5 nm) in lipid bilayers. Unlike selective AMPs, melittin is cytolytic to both bacterial and mammalian cells. Activates phospholipase A2 and causes mast cell degranulation (bee sting pain). Cancer research exploits its lytic activity with tumor-targeting delivery systems.", "primaryUses": [ "Research: membrane biophysics", "Anticancer research (nanoparticle conjugates)", "Broad-spectrum antimicrobial research", "Template for selective AMP design" ], "typicalDose": { "range": "N/A", "unit": "N/A", "frequency": "N/A", "route": "research only", "notes": "Not used clinically due to non-selective cytotoxicity." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "Habermann E. \"Bee and wasp venoms.\" Science. 1972;177(4046):314-322. PMID: 4113805.", "pmid": "4113805" }, { "type": "pubmed", "citation": "Duffy C, et al. \"Honeybee venom and melittin suppress growth factor receptor activation in HER2-enriched and triple-negative breast cancer.\" NPJ Precis Oncol. 2020;4:24. PMID: 32923684.", "pmid": "32923684" } ], "interactionCoverage": "unreviewed", "related": [ "magainin", "cecropin", "ll-37", "ziconotide" ], "lastReviewed": "2026-04-21", "publishedAt": "2026-04-21", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "menotropin", "name": "Menotropin", "aliases": [ "Menopur", "Repronex", "Humegon", "hMG", "human menopausal gonadotropin", "highly purified hMG" ], "tier": "mid", "category": "sexual-health", "subcategory": "urinary-derived gonadotropin", "class": "Highly purified urinary-derived human menopausal gonadotropin — a combination of FSH and LH (with some hCG contributing LH-like bioactivity) extracted from the urine of postmenopausal women.", "tagline": "The urine-derived FSH and LH preparation used for IVF ovarian stimulation, still about equal to recombinant FSH in trials.", "oneLiner": "Gonadotropins purified from the urine of postmenopausal women, carrying FSH and LH activity in one vial.", "sequence": null, "molecularFormula": null, "molecularWeight": 30000, "halfLife": { "value": 12, "unit": "hours", "range": "11 to 13 hours (FSH component)", "source": { "type": "label", "ref": "Menopur prescribing information, section 12.3 (DailyMed version 47, effective May 31, 2018; read September 30, 2026)" } }, "fdaStatus": "approved", "approvalDetails": "FDA-approved as Menopur (menotropins for injection), Ferring, BLA 021663. The current US label covers only the development of multiple follicles and pregnancy in ovulatory women as part of an assisted reproductive technology cycle; it starts at 225 IU a day and is not given above 450 IU a day.", "mechanism": "Combined FSHR agonism (supporting follicular recruitment and growth) and LH receptor agonism (supporting theca-cell androgen production, follicular maturation, and steroidogenesis in the late follicular phase). Clinically useful in patients with suppressed endogenous LH or in IVF protocols where LH supplementation is considered beneficial.", "primaryUses": [ "Development of multiple follicles and pregnancy in an assisted reproductive technology cycle (US label)" ], "typicalDose": { "range": "75–450", "unit": "IU/day (combined FSH activity)", "frequency": "daily", "route": "subcutaneous or intramuscular", "notes": "IVF: 150–300 IU/day SC starting dose, adjusted by response. Hypogonadotropic hypogonadism: 75 IU/day, titrated. Dosing is expressed as IU of FSH activity; the LH activity is proportionate in the menotropin preparation." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Menopur (menotropins for injection) Prescribing Information, sections 1 and 2. Ferring Pharmaceuticals (DailyMed version 47, effective May 31, 2018; read September 30, 2026)." }, { "type": "pubmed", "citation": "Devroey P, et al. \"A randomized assessor-blind trial comparing highly purified hMG and recombinant FSH in a GnRH antagonist cycle with compulsory single-blastocyst transfer.\" Fertil Steril, 2012;97(3):561-71. PMID: 22244781.", "pmid": "22244781" }, { "type": "pubmed", "citation": "Rao KA, et al. \"Clinical efficacy and safety of two highly purified human menopausal gonadotropins in women undergoing in vitro fertilization.\" Reprod Fertil, 2025;6(2). PMID: 40445794.", "pmid": "40445794" }, { "type": "pubmed", "citation": "Deeks ED. \"Highly Purified Human Menopausal Gonadotropin (Menopur(®)): A Profile of Its Use in Infertility.\" Clin Drug Investig, 2018;38(11):1077-1084. PMID: 30264288.", "pmid": "30264288" }, { "type": "pubmed", "citation": "Filicori M, et al. \"Luteinzing hormone activity in menotropins optimizes folliculogenesis and treatment in controlled ovarian stimulation.\" J Clin Endocrinol Metab, 2001;86(1):337-43. PMID: 11232021.", "pmid": "11232021" }, { "type": "pubmed", "citation": "Kirshenbaum M, et al. \"Recombinant follicular stimulating hormone plus recombinant luteinizing hormone versus human menopausal gonadotropins- does the source of LH bioactivity affect ovarian stimulation outcome?.\" Reprod Biol Endocrinol, 2021;19(1):182. PMID: 34886872.", "pmid": "34886872" }, { "type": "other", "citation": "US FDA, Drugs@FDA (openFDA): MENOPUR (menotropins for injection), BLA 021663, Ferring, prescription. Read September 30, 2026." }, { "type": "pubmed", "citation": "Al-Inany H, et al. \"Recombinant versus urinary gonadotrophins for triggering ovulation in assisted conception.\" Hum Reprod, 2005;20(8):2061-73. PMID: 16024539.", "pmid": "16024539" } ], "interactionCoverage": "partial", "related": [ "follitropin-alfa", "follitropin-beta", "urofollitropin", "lutropin-alfa", "hcg" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.2.1", "named": false, "wording": "luteinizing hormone (LH)", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "malesOnly": true, "remark": "Human menopausal gonadotrophin contains LH activity, and LH is named; FDA approval does not lift an S2 listing." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.2.1", "named": false, "wording": "luteinizing hormone (LH)", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "malesOnly": true, "remark": "Human menopausal gonadotrophin contains LH activity, and LH is named; FDA approval does not lift an S2 listing." } ], "moleculeClass": "protein", "moleculeClassBasis": "gonadotropin" }, { "id": "mgf", "name": "MGF", "aliases": [ "Mechano Growth Factor", "IGF-1Ec", "IGF-1 Ec variant" ], "tier": "mid", "category": "research", "subcategory": "IGF-1 splice variant", "class": "A muscle-specific splice variant of the IGF-1 gene produced in response to mechanical load, carrying the IGF-1 Ec exon sequence on the C-terminus.", "tagline": "The IGF-1 splice variant muscle makes after loading, sold online as a synthetic fragment that has never been given to a person in a study.", "oneLiner": "IGF-1Ec, an IGF-1 isoform produced after mechanical loading; research products are a synthetic 24-amino-acid peptide from its E domain.", "sequence": "Partial IGF-1 sequence with distinct Ec-exon C-terminus (YQPPSTNKNTKSQRRKGSTFEERK)", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": null, "range": "shorter than systemic IGF-1's when unbound; not measured in people", "source": { "type": "pmid", "pmid": "11915923", "cite": "Goldspink G, et al. \"Effects of activity on growth factor expression.\" Int J Sport Nutr Exerc Metab, 2001;11 Suppl:S21-7. PMID: 11915923." } }, "fdaStatus": "research-only", "approvalDetails": "Not approved anywhere. No published study has given MGF or its synthetic E-domain peptide to a person; the human data measure its expression in patients' tissue.", "mechanism": "MGF is generated by alternative splicing of the IGF-1 primary transcript following mechanical overload in skeletal muscle, producing an IGF-1 isoform with a unique C-terminal Ec extension. The Ec peptide appears to act independently of the IGF-1 receptor in the initial satellite-cell proliferation phase, while the IGF-1 portion of the full splice variant drives subsequent differentiation. Local, autocrine/paracrine action dominates — systemic administration of the unmodified peptide is largely ineffective because of near-immediate degradation.", "primaryUses": [ "Research peptide (no approved use)" ], "typicalDose": null, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Alagaratnam S, et al. \"Increased expression of IGF-1Ec with increasing colonic polyp dysplasia and colorectal cancer.\" J Cancer Res Clin Oncol, 2020;146(11):2861-2870. PMID: 32772171.", "pmid": "32772171" }, { "type": "pubmed", "citation": "Vassilakos G, et al. \"Biological activity of the e domain of the IGF-1Ec as addressed by synthetic peptides.\" Hormones (Athens), 2014;13(2):182-96. PMID: 24776619.", "pmid": "24776619" }, { "type": "pubmed", "citation": "Kandalla PK, et al. \"Mechano Growth Factor E peptide (MGF-E), derived from an isoform of IGF-1, activates human muscle progenitor cells and induces an increase in their fusion potential at different ages.\" Mech Ageing Dev, 2011;132(4):154-62. PMID: 21354439.", "pmid": "21354439" }, { "type": "pubmed", "citation": "Tang JJ, et al. \"Mechano growth factor, a splice variant of IGF-1, promotes neurogenesis in the aging mouse brain.\" Mol Brain, 2017;10(1):23. PMID: 28683812.", "pmid": "28683812" }, { "type": "pubmed", "citation": "Yang SY, et al. \"Different roles of the IGF-I Ec peptide (MGF) and mature IGF-I in myoblast proliferation and differentiation.\" FEBS Lett, 2002;522(1-3):156-60. PMID: 12095637.", "pmid": "12095637" }, { "type": "pubmed", "citation": "Hill M, et al. \"Expression and splicing of the insulin-like growth factor gene in rodent muscle is associated with muscle satellite (stem) cell activation following local tissue damage.\" J Physiol, 2003;549(Pt 2):409-18. PMID: 12692175.", "pmid": "12692175" }, { "type": "pubmed", "citation": "Goldspink G, et al. \"Effects of activity on growth factor expression.\" Int J Sport Nutr Exerc Metab, 2001;11 Suppl:S21-7. PMID: 11915923.", "pmid": "11915923" } ], "interactionCoverage": "unreviewed", "related": [ "peg-mgf", "igf-1-lr3", "igf-1-des" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.3", "named": true, "wording": "Mechano growth factors (MGFs)", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.3", "named": true, "wording": "Mechano growth factors (MGFs)", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "mk-677", "name": "MK-677", "aliases": [ "Ibutamoren", "Ibutamoren mesylate", "MK-0677", "MK0677", "LUM-201", "Nutrobal" ], "tier": "full", "category": "growth-hormone", "subcategory": "oral ghrelin receptor agonist (non-peptide)", "class": "Non-peptide small-molecule ghrelin receptor agonist with oral bioavailability — included in peptide compendia by convention.", "tagline": "An oral, non-peptide ghrelin-receptor agonist: it raised growth hormone and IGF-1 for months in trials and added lean mass in older adults, but failed in Alzheimer's and hip-fracture recovery, raised blood sugar and was never approved.", "oneLiner": "A small-molecule GHS-R1a agonist (ibutamoren) designed from GHRP-6, taken by mouth once a day: it lifted IGF-1 in more than a thousand trial participants but was never approved, and returns as LUM-201 in paediatric trials.", "sequence": null, "molecularFormula": "C27H36N4O5S", "molecularWeight": 528.67, "halfLife": { "value": null, "unit": null, "range": "not reported in the abstracts we hold", "notes": "In dogs one oral dose kept growth hormone raised for up to 6 hours and IGF-1 for longer; in people once-daily dosing kept IGF-1 raised across the day (1996-1997). The '~6 hour' figure given here before had no source." }, "fdaStatus": "discontinued", "approvalDetails": "Never approved anywhere. A hip-fracture trial was stopped early over a congestive heart failure signal (published 2011). FDA's advisory committee voted 13 to 1 against adding it to the 503A list (October 29, 2024); it is in 503A and 503B Category 2, and FDA states it is excluded from the dietary-supplement definition (warning letter, December 19, 2025). The same molecule is in paediatric trials as LUM-201.", "mechanism": "Non-peptide agonist at GHS-R1a (ghrelin receptor), mimicking endogenous ghrelin. Stimulates pulsatile GH release from anterior pituitary somatotrophs, elevates IGF-1, and activates hypothalamic AgRP/NPY neurons producing appetite stimulation. Unlike peptide GHRPs, MK-677 is orally active and has a 24-hour functional duration.", "primaryUses": [ "Pediatric GH deficiency (LUM-201 investigational)", "GH-axis research", "Community use for GH/IGF-1 elevation (not FDA-approved)" ], "typicalDose": { "range": "10–25", "unit": "mg", "frequency": "once daily", "route": "oral", "notes": "Community dosing. FDA has issued warning letters against consumer sales. Elevated appetite, water retention, and insulin resistance are common." }, "evidenceLevel": "medium", "sources": [ { "type": "Animal", "citation": "Jacks T, et al. \"MK-0677, a potent, novel, orally active growth hormone (GH) secretagogue: GH, insulin-like growth factor I, and other hormonal responses in beagles.\" Endocrinology, 1996;137(12):5284-9. PMID: 8940347.", "pmid": "8940347" }, { "type": "Human", "citation": "Chapman IM, et al. \"Stimulation of the growth hormone (GH)-insulin-like growth factor I axis by daily oral administration of a GH secretogogue (MK-677) in healthy elderly subjects.\" J Clin Endocrinol Metab, 1996;81(12):4249-57. PMID: 8954023.", "pmid": "8954023" }, { "type": "Human", "citation": "Copinschi G, et al. \"Effects of a 7-day treatment with a novel, orally active, growth hormone (GH) secretagogue, MK-677, on 24-hour GH profiles, insulin-like growth factor I, and adrenocortical function in normal young men.\" J Clin Endocrinol Metab, 1996;81(8):2776-82. PMID: 8768828.", "pmid": "8768828" }, { "type": "Animal", "citation": "Hickey GJ, et al. \"Repeat administration of the GH secretagogue MK-0677 increases and maintains elevated IGF-I levels in beagles.\" J Endocrinol, 1997;152(2):183-92. PMID: 9071975.", "pmid": "9071975" }, { "type": "Human", "citation": "Copinschi G, et al. \"Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in man.\" Neuroendocrinology, 1997;66(4):278-86. PMID: 9349662.", "pmid": "9349662" }, { "type": "Human", "citation": "Murphy MG, et al. \"MK-677, an orally active growth hormone secretagogue, reverses diet-induced catabolism.\" J Clin Endocrinol Metab, 1998;83(2):320-5. PMID: 9467534.", "pmid": "9467534" }, { "type": "Human", "citation": "Svensson J, et al. \"Two-month treatment of obese subjects with the oral growth hormone (GH) secretagogue MK-677 increases GH secretion, fat-free mass, and energy expenditure.\" J Clin Endocrinol Metab, 1998;83(2):362-9. PMID: 9467542.", "pmid": "9467542" }, { "type": "Human", "citation": "Svensson J, et al. \"Treatment with the oral growth hormone secretagogue MK-677 increases markers of bone formation and bone resorption in obese young males.\" J Bone Miner Res, 1998;13(7):1158-66. PMID: 9661080.", "pmid": "9661080" }, { "type": "Human", "citation": "Murphy MG, et al. \"Oral administration of the growth hormone secretagogue MK-677 increases markers of bone turnover in healthy and functionally impaired elderly adults. The MK-677 Study Group.\" J Bone Miner Res, 1999;14(7):1182-8. PMID: 10404019.", "pmid": "10404019" }, { "type": "Human", "citation": "Codner E, et al. \"Effects of oral administration of ibutamoren mesylate, a nonpeptide growth hormone secretagogue, on the growth hormone-insulin-like growth factor I axis in growth hormone-deficient children.\" Clin Pharmacol Ther, 2001;70(1):91-8. PMID: 11452249.", "pmid": "11452249" }, { "type": "Human", "citation": "Murphy MG, et al. \"Effect of alendronate and MK-677 (a growth hormone secretagogue), individually and in combination, on markers of bone turnover and bone mineral density in postmenopausal osteoporotic women.\" J Clin Endocrinol Metab, 2001;86(3):1116-25. PMID: 11238495.", "pmid": "11238495" }, { "type": "Human", "citation": "Bach MA, et al. \"The effects of MK-0677, an oral growth hormone secretagogue, in patients with hip fracture.\" J Am Geriatr Soc, 2004;52(4):516-23. PMID: 15066065.", "pmid": "15066065" }, { "type": "Human", "citation": "Sevigny JJ, et al. \"Growth hormone secretagogue MK-677: no clinical effect on AD progression in a randomized trial.\" Neurology, 2008;71(21):1702-8. PMID: 19015485.", "pmid": "19015485" }, { "type": "Human", "citation": "Adunsky A, et al. \"MK-0677 (ibutamoren mesylate) for the treatment of patients recovering from hip fracture: a multicenter, randomized, placebo-controlled phase IIb study.\" Arch Gerontol Geriatr, 2011;53(2):183-9. PMID: 21067829.", "pmid": "21067829" }, { "type": "Human", "citation": "Campbell GA, et al. \"Oral ghrelin receptor agonist MK-0677 increases serum insulin-like growth factor 1 in hemodialysis patients: a randomized blinded study.\" Nephrol Dial Transplant, 2018;33(3):523-530. PMID: 28340044.", "pmid": "28340044" }, { "type": "Animal", "citation": "Tian J, et al. \"MK0677, a Ghrelin Mimetic, Improves Neurogenesis but Fails to Prevent Hippocampal Lesions in a Mouse Model of Alzheimer's Disease Pathology.\" J Alzheimers Dis, 2019;72(2):467-478. PMID: 31594237.", "pmid": "31594237" }, { "type": "Human", "citation": "Bright GM, et al. \"Development of a Predictive Enrichment Marker for the Oral GH Secretagogue LUM-201 in Pediatric Growth Hormone Deficiency.\" J Endocr Soc, 2021;5(6):bvab030. PMID: 33982679.", "pmid": "33982679" }, { "type": "Human", "citation": "Cardaci TD, et al. \"LGD-4033 and MK-677 use impacts body composition, circulating biomarkers, and skeletal muscle androgenic hormone and receptor content: A case report.\" Exp Physiol, 2022;107(12):1467-1476. PMID: 36303408.", "pmid": "36303408" }, { "type": "Human", "citation": "Cobani E, et al. \"Hepatotoxicity induced by MK-677.\" BMJ Case Rep, 2025;18(7). PMID: 40675653.", "pmid": "40675653" }, { "type": "Human", "citation": "Kintz P, et al. \"Knowing the minimal detectable dose can facilitate the interpretation of a hair test result: II. Case example with ibutamoren (MK-677), a growth hormone secretagogue.\" Clin Chim Acta, 2026;578:120578. PMID: 40882886.", "pmid": "40882886" }, { "type": "pubmed", "citation": "Nass R, et al. \"Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial.\" Ann Intern Med, 2008;149(9):601-11. PMID: 18981485.", "pmid": "18981485" }, { "type": "fda-pi", "citation": "US FDA. Pharmacy Compounding Advisory Committee meeting, October 29, 2024: summary minutes, Section 503A Bulk Drug Substances List, ibutamoren mesylate (vote: 1 yes, 13 no)." }, { "type": "fda-pi", "citation": "US FDA. Warning letter to AgeBox Inc (MARCS-CMS 718252), December 19, 2025: undeclared ibutamoren mesylate found in iKids-Growth products; ibutamoren excluded from the definition of a dietary supplement under FD&C Act section 201(ff)(3)(B)(ii)." } ], "interactionCoverage": "partial", "related": [ "ipamorelin", "cjc-1295", "sermorelin", "macimorelin" ], "lastReviewed": "2026-09-27", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.2.4", "named": true, "wording": "ibutamoren (MK-677)", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.2.4", "named": true, "wording": "ibutamoren (MK-677)", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "small-molecule", "moleculeClassBasis": "small-molecule" }, { "id": "mod-grf-1-29", "name": "Mod GRF 1-29", "aliases": [ "CJC-1295 without DAC", "CJC-1295 no DAC", "Modified GRF(1-29)", "Sermorelin analog" ], "tier": "stub", "category": "growth-hormone", "subcategory": "short-acting GHRH analog", "class": "Tetrasubstituted GHRH(1-29) analog without the DAC linker — a short-acting research variant.", "tagline": "A short-acting GHRH analog — chemically identical to CJC-1295 but without the DAC albumin-binding linker — producing discrete GH pulses rather than sustained elevation.", "oneLiner": "The same four amino acid substitutions as CJC-1295 (D-Ala2, Gln8, Ala15, Leu27) applied to sermorelin's backbone, but lacking the DAC moiety — giving improved protease resistance over sermorelin while preserving pulsatile GH release kinetics.", "sequence": "H-Tyr-D-Ala-Asp-Ala-Ile-Phe-Thr-Gln-Ser-Tyr-Arg-Lys-Val-Leu-Ala-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Leu-Ser-Arg-NH2", "molecularFormula": "C152H252N44O42", "molecularWeight": 3367.92, "halfLife": { "value": null, "unit": null, "range": "not measured in humans", "notes": "No pharmacokinetic study of modified GRF 1-29 appears in PubMed. The '~30 minutes' and the one-to-three daily doses given here before had no source." }, "fdaStatus": "research-only", "approvalDetails": "Not approved. Not distinct from CJC-1295 in the chemistry literature; the community treats \"with DAC\" and \"without DAC\" as two separate products, while vendors often label Mod GRF 1-29 as \"CJC-1295 no DAC.\"", "mechanism": "GHRH receptor agonist. The four amino acid substitutions confer resistance to DPP-IV and other proteases while preserving the pulsatile GH-release profile that is considered more physiological than continuous stimulation. Typically stacked with ipamorelin or another GHRP.", "primaryUses": [ "Growth hormone axis research", "Community \"pulse\" protocols stacked with GHRPs" ], "typicalDose": { "range": "100–300", "unit": "mcg", "frequency": "1–3 times daily", "route": "subcutaneous", "notes": "Community dosing only. No clinical standard exists for this specific variant." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Alba M, et al. \"Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse.\" Am J Physiol Endocrinol Metab, 2006. PMID: 16822960.", "pmid": "16822960" }, { "type": "review", "citation": "Walker RF. \"Sermorelin: A better approach to management of adult-onset growth hormone insufficiency?\" Clin Interv Aging, 2006;1:307-308. PMID: 18046908.", "pmid": "18046908" } ], "interactionCoverage": "partial", "related": [ "cjc-1295", "ipamorelin", "sermorelin" ], "lastReviewed": "2026-04-18", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.2.4", "named": false, "wording": "growth hormone-releasing hormone (GHRH) and its analogues", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "A GHRH analogue sold as “CJC-1295 without DAC”; the List names CJC-1293 and CJC-1295 and covers every GHRH analogue." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.2.4", "named": false, "wording": "growth hormone-releasing hormone (GHRH) and its analogues", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "A GHRH analogue sold as “CJC-1295 without DAC”; the List names CJC-1293 and CJC-1295 and covers every GHRH analogue." } ], "moleculeClass": "peptide" }, { "id": "mots-c", "name": "MOTS-c", "aliases": [ "MOTSc", "Mitochondrial ORF of 12S rRNA-c" ], "tier": "full", "category": "longevity", "subcategory": "mitochondrial-derived peptide", "class": "Endogenous 16-amino-acid mitochondrial-derived peptide encoded within the 12S rRNA region of mitochondrial DNA.", "tagline": "A mitochondrially encoded peptide studied for its effects on metabolic homeostasis, insulin sensitivity, and exercise capacity.", "oneLiner": "A 16-amino-acid peptide encoded within the 12S rRNA region of mitochondrial DNA that regulates metabolic homeostasis through AMPK activation and appears to decline with age.", "sequence": "MRWQEMGYIFYPRKLR", "molecularFormula": "C101H152N28O22S2", "molecularWeight": 2174.7, "halfLife": { "value": null, "unit": null, "range": "undetermined in humans", "notes": "Endogenous peptide; pharmacokinetics of exogenous administration not well characterized." }, "fdaStatus": "research-only", "approvalDetails": "Not approved for any indication. Preclinical and early translational research only.", "mechanism": "Acts via AMPK activation to regulate glucose and fatty acid metabolism. In mouse models, MOTS-c administration prevents diet-induced obesity, improves insulin sensitivity, and enhances exercise capacity, in part through effects on skeletal muscle metabolic gene expression. Circulating MOTS-c declines with age in humans and has been proposed as a longevity-associated peptide.", "primaryUses": [ "Research into mitochondrial-nuclear signaling", "Metabolic disease models (preclinical)", "Exercise performance and aging (early human observational)" ], "typicalDose": { "range": "5–10", "unit": "mg", "frequency": "weekly (community)", "route": "subcutaneous", "notes": "Community/anecdotal dosing — no clinical trials have established a human dose. Not medical guidance." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Lee C, et al. \"The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance.\" Cell Metab, 2015;21(3):443-54. PMID: 25738459.", "pmid": "25738459" }, { "type": "pubmed", "citation": "Kim KH, et al. \"The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress.\" Cell Metab, 2018;28(3):516-524.e7. PMID: 29983246.", "pmid": "29983246" }, { "type": "pubmed", "citation": "Reynolds JC, et al. \"MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis.\" Nat Commun, 2021;12(1):470. PMID: 33473109.", "pmid": "33473109" }, { "type": "pubmed", "citation": "Kim SJ, et al. \"The mitochondrial-derived peptide MOTS-c is a regulator of plasma metabolites and enhances insulin sensitivity.\" Physiol Rep, 2019;7(13):e14171. PMID: 31293078.", "pmid": "31293078" }, { "type": "pubmed", "citation": "Zempo H, et al. \"A pro-diabetogenic mtDNA polymorphism in the mitochondrial-derived peptide, MOTS-c.\" Aging (Albany NY), 2021;13(2):1692-1717. PMID: 33468709.", "pmid": "33468709" }, { "type": "pubmed", "citation": "Dieli-Conwright CM, et al. \"Effect of aerobic and resistance exercise on the mitochondrial peptide MOTS-c in Hispanic and Non-Hispanic White breast cancer survivors.\" Sci Rep, 2021;11(1):16916. PMID: 34413391.", "pmid": "34413391" }, { "type": "pubmed", "citation": "Elhusseiny R, et al. \"Repeated Heat Stress Modulates the Levels of the Mitokines MOTS-C and FGF21 in Active Men during Calf Muscle Immobilization.\" Med Sci Sports Exerc, 2025;57(12):2764-2774. PMID: 40674654.", "pmid": "40674654" }, { "type": "pubmed", "citation": "Cuyàs E, et al. \"Circulating levels of MOTS-c in patients with breast cancer treated with metformin.\" Aging (Albany NY), 2022;15(4):892-897. PMID: 36490309.", "pmid": "36490309" }, { "type": "pubmed", "citation": "Kumagai H, et al. \"Mitochondrial-derived microprotein MOTS-c attenuates immobilization-induced skeletal muscle atrophy by suppressing lipid infiltration.\" Am J Physiol Endocrinol Metab, 2024;326(3):E207-E214. PMID: 38170165.", "pmid": "38170165" }, { "type": "pubmed", "citation": "Yin Y, et al. \"The mitochondrial-derived peptide MOTS-c relieves hyperglycemia and insulin resistance in gestational diabetes mellitus.\" Pharmacol Res, 2022;175:105987. PMID: 34798268.", "pmid": "34798268" }, { "type": "pubmed", "citation": "Yin Y, et al. \"Mitochondrial-Derived Peptide MOTS-c Suppresses Ovarian Cancer Progression by Attenuating USP7-Mediated LARS1 Deubiquitination.\" Adv Sci (Weinh), 2024;11(43):e2405620. PMID: 39321430.", "pmid": "39321430" }, { "type": "pubmed", "citation": "Zheng Y, et al. \"MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation.\" Front Endocrinol (Lausanne), 2023;14:1120533. PMID: 36761202.", "pmid": "36761202" } ], "interactionCoverage": "unreviewed", "related": [ "ss-31", "humanin" ], "lastReviewed": "2026-09-26", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S4.4.1", "named": true, "wording": "mitochondrial open reading frame of the 12S rRNA-c (MOTS-c)", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Listed as an AMPK activator alongside AICAR, not under S2 as is often claimed." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S4.4.1", "named": true, "wording": "mitochondrial open reading frame of the 12S rRNA-c (MOTS-c)", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Listed as an AMPK activator alongside AICAR, not under S2 as is often claimed." } ], "moleculeClass": "peptide" }, { "id": "na-selank-amidate", "name": "NA-Selank Amidate", "aliases": [ "N-Acetyl Selank Amidate", "Acetylated Selank" ], "tier": "stub", "category": "cognitive", "subcategory": "modified tuftsin-derived neuropeptide", "class": "An acetylated, amidated derivative of Selank with enhanced stability and bioavailability, designed for improved intranasal delivery and prolonged nootropic/anxiolytic activity.", "tagline": "An enhanced Selank derivative — N-terminal acetylation and C-terminal amidation improve protease resistance and nasal absorption, extending the anxiolytic and nootropic profile.", "oneLiner": "A chemically modified version of Selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro) with N-acetyl and C-amide terminal modifications conferring greater enzymatic stability and enhanced CNS penetration via intranasal delivery.", "sequence": "Ac-Thr-Lys-Pro-Arg-Pro-Gly-Pro-NH2", "molecularFormula": "C33H57N11O9", "molecularWeight": 755.9, "halfLife": { "value": null, "unit": null, "range": "Extended vs. native Selank (~minutes → estimated hours)", "notes": "Terminal modifications reduce aminopeptidase and carboxypeptidase degradation, extending functional duration." }, "fdaStatus": "research-only", "approvalDetails": "Not approved by any regulatory body. Available through research peptide vendors. Parent compound Selank is approved in Russia.", "mechanism": "Same as Selank: modulates GABA-A receptor allosteric sites, increases BDNF expression, and influences IL-6 and enkephalin metabolism. The N-acetyl modification blocks aminopeptidase degradation; the C-amide blocks carboxypeptidase attack. Net result is longer residence time at target receptors and improved intranasal-to-CNS delivery.", "primaryUses": [ "Anxiolytic nootropic (research/community use)", "Enhanced Selank analog research", "BDNF modulation studies" ], "typicalDose": { "range": "200–600", "unit": "mcg", "frequency": "1–2 times daily", "route": "intranasal", "notes": "Community-reported dosing. No clinical trials for this specific derivative." }, "evidenceLevel": "low", "sources": [ { "type": "other", "citation": "No independent publication exists for the acetylated and amidated form; what is known is derived from the Selank literature cited on that entry." } ], "interactionCoverage": "unreviewed", "related": [ "selank", "semax", "noopept" ], "lastReviewed": "2026-04-20", "publishedAt": "2026-04-20", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "nad-plus", "name": "NAD+", "aliases": [ "Nicotinamide Adenine Dinucleotide", "NAD", "NAD plus", "β-nicotinamide adenine dinucleotide" ], "tier": "full", "category": "longevity", "subcategory": "pyridine nucleotide coenzyme", "class": "Note: NAD+ is a pyridine-nucleotide coenzyme, not a peptide. It is included here because injectable and IV NAD+ is universally grouped with peptide therapeutics in longevity, wellness, and biohacker contexts.", "tagline": "The coenzyme every cell runs on, sold as IV drips and injections: one small 2026 heart-failure trial is the only controlled test of NAD+ itself.", "oneLiner": "A coenzyme for hundreds of redox reactions and the fuel of sirtuins, PARPs and CD38; its levels fall with age, and most research uses oral precursors rather than the IV NAD+ clinics sell.", "sequence": "Not applicable — NAD+ is a dinucleotide (nicotinamide mononucleotide linked to adenosine monophosphate via a pyrophosphate bridge), not a peptide.", "molecularFormula": "C21H27N7O14P2", "molecularWeight": 663.43, "halfLife": { "value": null, "unit": null, "range": "not reported in the abstracts we hold", "notes": "A 2026 systematic review found only a pharmacokinetic pilot of IV NAD+ without clinical outcomes. The previous note about precursor pathways was not sourced for NAD+ itself." }, "fdaStatus": "research-only", "approvalDetails": "Not FDA-approved for any use. FDA's 503A list (updated May 14, 2026) places nicotinamide adenine dinucleotide (NAD) and NAD disodium in Category 1, under evaluation, where its interim policy does not act against pharmacy compounding; beta-nicotinamide adenine dinucleotide is in Category 3. The oral precursor nicotinamide riboside is sold as a supplement.", "mechanism": "Acts as a cofactor in hundreds of enzymatic redox reactions (hydride transfer between NAD+/NADH) central to glycolysis, TCA cycle, and oxidative phosphorylation. Also a substrate for sirtuins (NAD+-dependent deacetylases implicated in longevity signaling), PARP enzymes (DNA repair), and CD38 (immune signaling). Cellular NAD+ declines with age in many tissues, which has motivated investigation of NAD+ restoration as a geroscience intervention. Exogenous NAD+ administration likely works indirectly through precursor metabolites rather than direct cellular uptake of intact NAD+.", "primaryUses": [ "IV wellness protocols for energy and cognitive support", "Investigational adjunct in addiction recovery (primarily clinic-based, limited RCT evidence)", "Anti-aging and longevity protocols (unestablished efficacy)", "Investigational in neurodegenerative conditions (early-phase trials)" ], "typicalDose": { "range": "100–1000", "unit": "mg", "frequency": "variable; 1–5x weekly IV or daily SC", "route": "IV (most common), subcutaneous, or intramuscular", "notes": "IV dosing commonly 250–1000 mg per infusion over 1–4 hours. Subcutaneous compounded protocols typically 50–100 mg per injection. Flushing, nausea, and chest tightness are common with faster IV infusion rates. No FDA-established dose." }, "evidenceLevel": "medium", "sources": [ { "type": "Review", "citation": "Rajman L, et al. \"Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence.\" Cell Metab, 2018;27(3):529-547. PMID: 29514064.", "pmid": "29514064" }, { "type": "Animal", "citation": "Liu L, et al. \"Quantitative Analysis of NAD Synthesis-Breakdown Fluxes.\" Cell Metab, 2018;27(5):1067-1080.e5. PMID: 29685734.", "pmid": "29685734" }, { "type": "Review", "citation": "Braidy N, et al. \"Role of Nicotinamide Adenine Dinucleotide and Related Precursors as Therapeutic Targets for Age-Related Degenerative Diseases: Rationale, Biochemistry, Pharmacokinetics, and Outcomes.\" Antioxid Redox Signal, 2019;30(2):251-294. PMID: 29634344.", "pmid": "29634344" }, { "type": "Animal", "citation": "Bugarski M, et al. \"Changes in NAD and Lipid Metabolism Drive Acidosis-Induced Acute Kidney Injury.\" J Am Soc Nephrol, 2021;32(2):342-356. PMID: 33478973.", "pmid": "33478973" }, { "type": "Animal", "citation": "Li DJ, et al. \"NAD(+)-boosting therapy alleviates nonalcoholic fatty liver disease via stimulating a novel exerkine Fndc5/irisin.\" Theranostics, 2021;11(9):4381-4402. PMID: 33754067.", "pmid": "33754067" }, { "type": "Animal", "citation": "Yaku K, et al. \"Nicotinamide riboside and nicotinamide mononucleotide facilitate NAD(+) synthesis via enterohepatic circulation.\" Sci Adv, 2025;11(12):eadr1538. PMID: 40117359.", "pmid": "40117359" }, { "type": "Animal", "citation": "Lei Y, et al. \"NAD(+) biosynthesis and mitochondrial repair in acute kidney injury via ultrasound-responsive thylakoid-integrating liposomes.\" Nat Biomed Eng, 2025;9(10):1740-1757. PMID: 40461655.", "pmid": "40461655" }, { "type": "Human", "citation": "Yu X, et al. \"Effect of Nicotinamide Adenine Dinucleotide on Heart Failure Caused by Ischemic Cardiomyopathy: A Randomized, Placebo-Controlled Trial.\" Am J Cardiovasc Drugs, 2026;26(1):97-106. PMID: 40954388.", "pmid": "40954388" }, { "type": "Human", "citation": "Reyna K, et al. \"Intravenous infusion of nicotinamide adenine dinucleotide (NAD(+)) versus nicotinamide riboside (NR): a retrospective tolerability pilot study in a real-world setting.\" Front Aging, 2026;7:1652582. PMID: 41704678.", "pmid": "41704678" }, { "type": "Review", "citation": "Gallagher C, et al. \"NAD⁺ supplementation for anti-aging and wellness: A PRISMA-guided systematic review of preclinical and clinical evidence.\" Ageing Res Rev, 2026;116:103057. PMID: 41655607.", "pmid": "41655607" } ], "interactionCoverage": "partial", "related": [ "glutathione", "ss-31", "mots-c" ], "lastReviewed": "2026-09-27", "publishedAt": "2026-04-20", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Not a peptide. Sold as a supplement and compounded for injection, never approved as a drug; how S0 treats it has not been decided. Separately, any infusion or injection of more than 100 mL per 12 hours is a prohibited method (M2.2) unless received in hospital treatment, surgery or clinical investigations." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Not a peptide. Sold as a supplement and compounded for injection, never approved as a drug; how S0 treats it has not been decided. Separately, any infusion or injection of more than 100 mL per 12 hours is a prohibited method (M2.2) unless received in hospital treatment, surgery or clinical investigations." } ], "moleculeClass": "small-molecule", "moleculeClassBasis": "coenzyme" }, { "id": "nafarelin", "name": "Nafarelin", "aliases": [ "Synarel" ], "tier": "stub", "category": "sexual-health", "subcategory": "GnRH agonist", "class": "Synthetic GnRH agonist with a 3-(2-naphthyl)-D-Ala substitution at position 6, formulated as an intranasal spray for twice-daily administration.", "tagline": "Pfizer's Synarel — the only FDA-approved intranasal GnRH agonist. Approved for endometriosis and central precocious puberty; offers a depot-free alternative to injectable leuprolide for patients who prefer nasal dosing.", "oneLiner": "A synthetic GnRH agonist with a 3-(2-naphthyl)-D-alanine substitution at position 6 that increases potency relative to native GnRH while permitting clinically useful intranasal bioavailability. Marketed in the US as Synarel nasal spray (Pfizer, formerly Syntex/Roche). FDA-approved for endometriosis (6 months) and central precocious puberty in children. Offers a needle-free delivery option but requires strict twice-daily adherence.", "sequence": "pGlu-His-Trp-Ser-Tyr-D-Nal(2)-Leu-Arg-Pro-Gly-NH2", "molecularFormula": "C66H83N17O13", "molecularWeight": 1322.5, "halfLife": { "value": 3, "unit": "hours", "range": "~3 hours (plasma after intranasal)", "notes": "Intranasal bioavailability is approximately 2.8%; twice-daily dosing achieves sustained hypogonadism." }, "fdaStatus": "approved", "approvalDetails": "FDA-approved as Synarel (nafarelin acetate nasal solution, Pfizer, first approved 1990) for management of endometriosis, including pain relief and reduction of endometriotic lesions (approved for a maximum treatment duration of 6 months); and for treatment of central precocious puberty in children of both sexes.", "mechanism": "Pituitary GnRHR agonism — produces an initial gonadotropin flare then receptor desensitization and hypogonadism, equivalent in effect to injectable GnRH agonists. Intranasal absorption achieves sufficient plasma concentrations when dosed twice daily.", "primaryUses": [ "Endometriosis (pain and lesion reduction, maximum 6-month course)", "Central precocious puberty (pediatric)" ], "typicalDose": { "range": "400 (endometriosis); 1600–1800 (CPP)", "unit": "mcg/day", "frequency": "twice daily (one spray each nostril BID for endometriosis; higher doses split across multiple sprays for CPP)", "route": "intranasal spray", "notes": "Endometriosis: one spray (200 mcg) in one nostril in the morning and one spray in the other nostril in the evening (total 400 mcg/day). CPP: two sprays each nostril three times daily (total 1800 mcg/day). Treatment initiated between menstrual days 2 and 4 for endometriosis to avoid mid-cycle ovulation. Nasal decongestants should be delayed at least 30 minutes after dosing." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Synarel (nafarelin acetate) Nasal Solution Prescribing Information. Pfizer." }, { "type": "pubmed", "citation": "Henzl MR, et al. \"Administration of nasal nafarelin as compared with oral danazol for endometriosis.\" N Engl J Med, 1988;318:485-489. PMID: 2963213.", "pmid": "2963213" } ], "interactionCoverage": "partial", "related": [ "leuprolide", "triptorelin", "histrelin", "gonadorelin" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.2.1", "named": true, "wording": "nafarelin", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "malesOnly": true, "monitoring": "GnRH analogues in female athletes under 18, in and out of competition" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.2.1", "named": true, "wording": "nafarelin", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "malesOnly": true, "monitoring": "GnRH analogues in female athletes under 18, in and out of competition" } ], "moleculeClass": "peptide" }, { "id": "navepegritide", "name": "Navepegritide", "aliases": [ "Yuviwel", "TransCon CNP", "ACP-015" ], "tier": "stub", "category": "growth-hormone", "subcategory": "PEGylated CNP analog (bone growth)", "class": "Navepegritide is a long-acting PEGylated CNP prodrug — FDA-approved in February 2026 as a once-weekly alternative to daily vosoritide for achondroplasia.", "tagline": "The weekly achondroplasia treatment — a PEGylated CNP prodrug approved in 2026 that provides continuous growth plate stimulation with once-weekly dosing.", "oneLiner": "A PEGylated prodrug of CNP using Ascendis Pharma's TransCon technology that provides sustained CNP exposure over a weekly dosing interval, FDA-approved February 2026 for achondroplasia in children >=2 years with open epiphyses.", "sequence": "CNP-38 conjugated to multi-arm PEG carrier via autocleavable linker", "molecularFormula": "Prodrug conjugate (CNP-38 + PEG carrier)", "molecularWeight": null, "halfLife": { "value": 95, "unit": "hours", "range": "80-110 hours", "notes": "TransCon linker auto-cleaves with first-order kinetics, releasing active CNP continuously over the weekly dosing interval." }, "fdaStatus": "approved", "approvalDetails": "FDA-approved February 27, 2026 as Yuviwel under Accelerated Approval for children >=2 years with achondroplasia and open epiphyses. Developed by Ascendis Pharma.", "mechanism": "Prodrug that releases unmodified CNP continuously over one week. Released CNP binds NPR-B on growth plate chondrocytes, inhibiting the overactive FGFR3-MAPK pathway in achondroplasia. Same MOA as vosoritide but with sustained weekly exposure.", "primaryUses": [ "Achondroplasia in children >=2 years (FDA-approved 2026)", "Once-weekly alternative to daily vosoritide" ], "typicalDose": { "range": "varies by weight band", "unit": "mcg/kg", "frequency": "once weekly", "route": "subcutaneous", "notes": "Reconstituted from lyophilized powder. Weight-banded dosing." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Ascendis Pharma. Yuviwel (navepegritide) Prescribing Information. FDA, February 2026." } ], "interactionCoverage": "none-found", "related": [ "vosoritide", "cnp", "somatropin", "lonapegsomatropin" ], "lastReviewed": "2026-04-21", "publishedAt": "2026-04-21", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide-conjugate", "moleculeClassBasis": "CNP-38 conjugated" }, { "id": "nesiritide", "name": "Nesiritide", "aliases": [ "Natrecor", "recombinant human B-type natriuretic peptide", "rhBNP", "Scios-1" ], "tier": "mid", "category": "cardiovascular", "subcategory": "Natriuretic peptide — guanylate cyclase-A (NPR-A) agonist", "class": "Recombinant human B-type natriuretic peptide (BNP) — the 32-amino-acid cardiac hormone secreted by ventricular myocytes in response to wall stress — produced in E. coli and developed as an IV vasodilator for acute decompensated heart failure.", "tagline": "Recombinant human B-type natriuretic peptide, sold in the US as Natrecor for acute heart failure. In the 7,141-patient ASCEND-HF trial it did not change death or readmission and had only a small, non-significant effect on breathlessness; Drugs@FDA lists Natrecor as discontinued.", "oneLiner": "Recombinant human B-type natriuretic peptide, given by intravenous infusion and sold in the US as Natrecor for early relief of breathlessness in acute heart failure. A 2005 meta-analysis linked it to worsening kidney function; the 7,141-patient ASCEND-HF trial found no effect on death or readmission, no kidney harm, more hypotension and a small, non-significant effect on breathlessness. Drugs@FDA lists Natrecor as discontinued.", "sequence": "SPKMVQGSGCFGRKMDRISSSSGLGCKVLRRH (32 residues; disulfide bond Cys10-Cys26 forms a 17-residue ring)", "molecularFormula": "C143H244N50O42S4", "molecularWeight": 3464.01, "halfLife": { "value": null, "unit": null, "range": "about 18 minutes", "source": { "type": "pmid", "pmid": "15992106", "cite": "Hobbs RE, et al. \"Therapeutic potential of nesiritide (recombinant b-type natriuretic peptide) in the treatment of heart failure.\" Expert Opin Investig Drugs, 1999;8(7):1063-72. PMID: 15992106." } }, "fdaStatus": "discontinued", "approvalDetails": "Natrecor (NDA 020920) was approved in the US for early relief of dyspnea in acute heart failure; Drugs@FDA now lists it as discontinued (openFDA, read September 30, 2026).", "mechanism": "Binds natriuretic peptide receptor A (NPR-A / GC-A / NPR1), a membrane-bound guanylate cyclase, on vascular smooth muscle, renal tubule, and adrenal cortex. Receptor activation raises intracellular cGMP, which activates protein kinase G, phosphorylates IP3 receptor and other targets, and produces: (1) arterial and venous vasodilation with reduction in preload and afterload; (2) natriuresis and diuresis through direct tubular effects on sodium reabsorption; (3) suppression of renin release, aldosterone secretion, and sympathetic nervous system activity. Net hemodynamic effect in acute heart failure is reduced pulmonary capillary wedge pressure and modest rise in cardiac output without positive inotropy. Clearance is via NPR-C-mediated endocytosis and neprilysin cleavage — the latter is the rationale for the sacubitril/valsartan approach, which inhibits neprilysin to augment endogenous BNP and ANP signalling rather than infusing exogenous peptide.", "primaryUses": [ "Acute heart failure with breathlessness (historical; Natrecor is discontinued in the US)" ], "typicalDose": { "range": "0.01", "unit": "mcg/kg/min", "frequency": "continuous infusion", "route": "intravenous", "notes": "The infusion rate used in the VMAC trial and a 2008 surgical trial." }, "evidenceLevel": "high", "sources": [ { "type": "fda", "citation": "US FDA, Drugs@FDA (openFDA): NATRECOR (nesiritide), Scios LLC, NDA 020920, original approval August 10, 2001, marketing status Discontinued. Read September 30, 2026." }, { "type": "pubmed", "citation": "O'Connor CM, et al. \"Effect of nesiritide in patients with acute decompensated heart failure.\" N Engl J Med, 2011;365(1):32-43. PMID: 21732835.", "pmid": "21732835" }, { "type": "pubmed", "citation": "Sackner-Bernstein JD, et al. \"Risk of worsening renal function with nesiritide in patients with acutely decompensated heart failure.\" Circulation, 2005;111(12):1487-91. PMID: 15781736.", "pmid": "15781736" }, { "type": "pubmed", "citation": "Hobbs RE, et al. \"An update on nesiritide for treatment of decompensated heart failure.\" Expert Opin Investig Drugs, 2001;10(5):935-42. PMID: 11322867.", "pmid": "11322867" }, { "type": "pubmed", "citation": "Beaver TM, et al. \"Nesiritide following maze and mitral valve surgery.\" J Card Surg, 2008;23(5):431-6. PMID: 18928481.", "pmid": "18928481" }, { "type": "pubmed", "citation": "Yao L, et al. \"Influence of recombinant human B-type natriuretic peptide on improving ventricular function in patients with ST elevation myocardial infarction.\" Eur Rev Med Pharmacol Sci, 2023;27(8):3420-3429. PMID: 37140291.", "pmid": "37140291" }, { "type": "pubmed", "citation": "Hobbs RE, et al. \"Therapeutic potential of nesiritide (recombinant b-type natriuretic peptide) in the treatment of heart failure.\" Expert Opin Investig Drugs, 1999;8(7):1063-72. PMID: 15992106.", "pmid": "15992106" }, { "type": "other", "citation": "ASHP Drug Shortages, Nesiritide Injection (created June 20, 2018): Janssen is discontinuing Natrecor powder for injection. Read September 30, 2026." } ], "interactionCoverage": "studied", "related": [ "carperitide", "ularitide" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "FDA-approved as Natrecor (NDA 020920, August 10, 2001) and now discontinued in the US; whether an approval is current anywhere is not verified here." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "FDA-approved as Natrecor (NDA 020920, August 10, 2001) and now discontinued in the US; whether an approval is current anywhere is not verified here." } ], "moleculeClass": "peptide" }, { "id": "neuropeptide-y", "name": "Neuropeptide Y", "aliases": [ "NPY", "Neuropeptide Tyrosine" ], "tier": "mid", "category": "cognitive", "subcategory": "Endogenous neuropeptide", "class": "Neuropeptide Y is one of the most abundant neuropeptides in the mammalian brain, regulating appetite, stress resilience, anxiety, circadian rhythms, and vasoconstriction.", "tagline": "The brain's most abundant neuropeptide — a 36-amino-acid master regulator of appetite, stress resilience, and anxiety that connects metabolic and cognitive peptide networks.", "oneLiner": "A 36-amino-acid peptide and one of the most abundant neuropeptides in the CNS, acting through Y1-Y5 receptors to powerfully stimulate appetite, reduce anxiety, enhance stress resilience, and modulate circadian rhythms and sympathetic vasoconstriction.", "sequence": "YPSKPDNPGEDAPAEDMARYYSALRHYINLITRQRY-amide", "molecularFormula": "C190H287N55O57", "molecularWeight": 4271.68, "halfLife": { "value": null, "unit": null, "range": "no figure in the sources read; the 2022 exercise study reports it is considerably shorter than immunoassays had established", "source": { "type": "pmid", "pmid": "35180646", "cite": "Sauvage A, et al. \"Kinetics of neuropeptide Y, catecholamines, and physiological responses during moderate and heavy intensity exercises.\" Neuropeptides, 2022;93:102232. PMID: 35180646." } }, "fdaStatus": "research-only", "approvalDetails": "Not approved as a drug anywhere; no application appears in Drugs@FDA (read October 1, 2026). It has been given to people only in research, including one randomised nasal-spray trial in depression.", "mechanism": "Binds five receptor subtypes (Y1, Y2, Y4, Y5, Y6) — all Gi/o-coupled GPCRs. Y1 activation in the amygdala produces anxiolysis. Y1/Y5 activation in the hypothalamic arcuate and paraventricular nuclei potently stimulates food intake (the strongest known orexigenic signal). Peripherally, NPY is co-released with norepinephrine from sympathetic nerves, producing potent vasoconstriction.", "primaryUses": [ "Endogenous appetite regulation (most potent known orexigenic peptide)", "Stress resilience and anxiety modulation (high NPY = resilience to PTSD)", "Circadian rhythm regulation", "Sympathetic vasoconstriction (co-transmitter with norepinephrine)" ], "typicalDose": { "range": null, "unit": null, "frequency": null, "route": null, "notes": "Not a medicine. The one randomised trial insufflated a single 6.8 mg dose (PMID 33009815)." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Mathé AA, et al. \"A Randomized Controlled Trial of Intranasal Neuropeptide Y in Patients With Major Depressive Disorder.\" Int J Neuropsychopharmacol, 2020;23(12):783-790. PMID: 33009815.", "pmid": "33009815" }, { "type": "pubmed", "citation": "Morgan CA 3rd, et al. \"Neuropeptide-Y, cortisol, and subjective distress in humans exposed to acute stress: replication and extension of previous report.\" Biol Psychiatry, 2002;52(2):136-42. PMID: 12114005.", "pmid": "12114005" }, { "type": "pubmed", "citation": "Eugster PJ, et al. \"Kinetics of neuropeptide Y, catecholamines, and physiological responses during moderate and heavy intensity exercises.\" Neuropeptides, 2022;92:102232. PMID: 35180646.", "pmid": "35180646" }, { "type": "pubmed", "citation": "Gu J, et al. \"Neuropeptide tyrosine (NPY)--a major cardiac neuropeptide.\" Lancet, 1983;1(8332):1008-10. PMID: 6133058.", "pmid": "6133058" }, { "type": "pubmed", "citation": "Tatemoto K, et al. \"Neuropeptide Y--a novel brain peptide with structural similarities to peptide YY and pancreatic polypeptide.\" Nature, 1982;296(5858):659-60. PMID: 6896083.", "pmid": "6896083" } ], "interactionCoverage": "unreviewed", "related": [ "pyy", "ghrelin", "orexin-a", "cholecystokinin" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-21", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "neurotensin", "name": "Neurotensin", "aliases": [ "NT", "NTS" ], "tier": "stub", "category": "cognitive", "subcategory": "Endogenous neuropeptide", "class": "Neurotensin is a dual gut-brain peptide that modulates dopamine neurotransmission, pain perception, and fat absorption — a key link between metabolic and psychiatric peptide networks.", "tagline": "A gut-brain peptide that modulates dopamine transmission, pain sensitivity, and fat absorption — linking metabolic health to schizophrenia and addiction research.", "oneLiner": "A 13-amino-acid peptide found in the brain and GI tract that modulates dopaminergic neurotransmission, produces non-opioid analgesia, promotes fat absorption, and is a research target for schizophrenia and addiction.", "sequence": "pELYENKPRRPYIL", "molecularFormula": "C78H121N21O20", "molecularWeight": 1672.9, "halfLife": { "value": 3, "unit": "minutes", "range": "1.5-5 minutes", "notes": "Rapidly degraded by metalloendopeptidases. The C-terminal hexapeptide NT8-13 retains full biological activity." }, "fdaStatus": "research-only", "approvalDetails": "Not approved as a drug. NTS1 receptor agonists are in preclinical development for analgesia and antipsychotic effects. NT-PRRT is in clinical trials for neurotensin receptor-positive cancers.", "mechanism": "Binds NTS1 (high-affinity, Gq-coupled — mediates analgesia and dopamine modulation), NTS2 (mediates analgesia), and NTS3/sortilin. In the VTA, NT enhances dopamine neuron firing. In the gut, promotes fat absorption.", "primaryUses": [ "Endogenous modulation of dopaminergic neurotransmission", "Non-opioid analgesia research", "Fat absorption and GI motility regulation", "Schizophrenia research", "Cancer targeting (NT-PRRT)" ], "typicalDose": { "range": "N/A", "unit": "N/A", "frequency": "N/A", "route": "endogenous", "notes": "Not used therapeutically. Plasma NT rises 2-3-fold after a fat-rich meal." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "Carraway R, Leeman SE. \"The isolation of a new hypotensive peptide, neurotensin, from bovine hypothalami.\" J Biol Chem. 1973;248(19):6854-6861. PMID: 4745447.", "pmid": "4745447" }, { "type": "review", "citation": "Boules M, et al. \"Diverse roles of neurotensin agonists in the central nervous system.\" Front Endocrinol. 2013;4:36. PMID: 23526754.", "pmid": "23526754" } ], "interactionCoverage": "unreviewed", "related": [ "neuropeptide-y", "cholecystokinin", "substance-p", "beta-endorphin" ], "lastReviewed": "2026-04-21", "publishedAt": "2026-04-21", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "nisin", "name": "Nisin", "aliases": [ "Nisin A", "Nisaplin" ], "tier": "mid", "category": "immune", "subcategory": "lantibiotic antimicrobial peptide", "class": "A 34-amino-acid lantibiotic (lanthionine-containing antibiotic) produced by Lactococcus lactis, widely used as a food preservative and studied as a pharmaceutical antimicrobial.", "tagline": "The food-grade antimicrobial peptide — a 34-amino-acid lantibiotic used in food preservation worldwide for 50+ years, with emerging pharmaceutical applications against MRSA and biofilms.", "oneLiner": "A 34-amino-acid polycyclic antimicrobial peptide produced by Lactococcus lactis, containing unusual lanthionine and methyl-lanthionine bridges, with a dual mechanism of lipid II binding and pore formation.", "sequence": "34 amino acids with 5 lanthionine/methyl-lanthionine rings; ITSISLCTPGCKTGALMGCNMKTATCHCSIHVSK", "molecularFormula": "C143H230N42O37S7", "molecularWeight": 3354.1, "halfLife": { "value": null, "unit": null, "range": "not reported in the sources read; it is eaten rather than injected", "source": { "type": "none", "note": "searched PubMed on October 1, 2026; no human half-life figure in the sources read" } }, "fdaStatus": "food-additive", "approvalDetails": "Not a drug and not a dietary supplement in the United States. Nisin preparation is affirmed as generally recognized as safe for one food use, in 21 CFR 184.1538, read in the eCFR on October 1, 2026: as an antimicrobial to stop Clostridium botulinum spores growing in pasteurized cheese spreads, at a level delivering no more than 250 parts per million of nisin in the finished product. The regulation dates from 53 FR 11250 (April 6, 1988), last amended at 88 FR 17724 (March 24, 2023). It is E234 in the EU.", "mechanism": "Dual mechanism: (1) Binds lipid II (the same peptidoglycan precursor target as vancomycin) with high affinity, sequestering it and blocking cell wall synthesis; (2) Uses the lipid II-nisin complex to form pores (2–2.5 nm diameter) in the bacterial membrane, causing rapid ion efflux and cell death. This dual action makes resistance development difficult. Active against gram-positive bacteria; gram-negatives are protected by the outer membrane.", "primaryUses": [ "Food preservation (dairy, meat, beverages)", "Anti-MRSA research", "Anti-biofilm strategies", "Mastitis treatment research (veterinary)" ], "typicalDose": { "range": null, "unit": null, "frequency": null, "route": null, "notes": "A food additive, limited by 21 CFR 184.1538 to no more than 250 parts per million of nisin in the finished cheese spread. No medical dose is established." }, "evidenceLevel": "high", "sources": [ { "type": "regulation", "citation": "21 CFR 184.1538, Nisin preparation, read in the eCFR on October 1, 2026 (53 FR 11250, April 6, 1988; last amended 88 FR 17724, March 24, 2023)." }, { "type": "pubmed", "citation": "Fernández L, et al. \"The bacteriocin nisin, an effective agent for the treatment of staphylococcal mastitis during lactation.\" J Hum Lact, 2008;24(3):311-6. PMID: 18689718.", "pmid": "18689718" }, { "type": "pubmed", "citation": "Cao LT, et al. \"Efficacy of nisin in treatment of clinical mastitis in lactating dairy cows.\" J Dairy Sci, 2007;90(8):3980-5. PMID: 17639009.", "pmid": "17639009" }, { "type": "pubmed", "citation": "Józefiak D, et al. \"Dietary nisin modulates the gastrointestinal microbial ecology and enhances growth performance of the broiler chickens.\" PLoS One, 2013;8(12):e85347. PMID: 24376878.", "pmid": "24376878" }, { "type": "pubmed", "citation": "O'Sullivan JN, et al. \"Nisin J, a Novel Natural Nisin Variant, Is Produced by Staphylococcus capitis Sourced from the Human Skin Microbiota.\" J Bacteriol, 2020;202(3). PMID: 31740495.", "pmid": "31740495" }, { "type": "pubmed", "citation": "Shin JM, et al. \"Biomedical applications of nisin.\" J Appl Microbiol, 2016;120(6):1449-65. PMID: 26678028.", "pmid": "26678028" }, { "type": "pubmed", "citation": "Breukink E, et al. \"Lipid II as a target for antibiotics.\" Nat Rev Drug Discov, 2006;5(4):321-32. PMID: 16531990.", "pmid": "16531990" } ], "interactionCoverage": "studied", "related": [ "vancomycin", "bacitracin", "ll-37", "polymyxin-b" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-20", "fdaApproved": false, "approvedElsewhere": "", "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "A food preservative (E 234; GRAS in the US), not a drug." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "A food preservative (E 234; GRAS in the US), not a drug." } ], "moleculeClass": "peptide" }, { "id": "noopept", "name": "Noopept", "aliases": [ "GVS-111", "Omberacetam", "N-phenylacetyl-L-prolylglycine ethyl ester" ], "tier": "full", "category": "cognitive", "subcategory": "prolyl dipeptide nootropic", "class": "A proline-containing dipeptide ethyl ester — structurally a dipeptide despite being often grouped with racetams.", "tagline": "A Russian capped-dipeptide nootropic (omberacetam) with rodent memory data, two small open human studies, and a habit of turning up in US supplements.", "oneLiner": "A dipeptide (N-phenylacetyl-L-prolylglycine ethyl ester) developed in Russia in the 1990s, included in peptide compendia by convention; metabolized to cycloprolylglycine, the endogenous form of which has nootropic activity.", "sequence": "N-phenylacetyl-Pro-Gly-OEt", "molecularFormula": "C17H22N2O4", "molecularWeight": 318.37, "halfLife": { "value": 30, "unit": "minutes", "range": "~30 minutes parent (longer for active metabolite)", "notes": "Rapidly metabolized to cycloprolylglycine (CPG) — the endogenous neuropeptide believed to mediate most of the activity." }, "fdaStatus": "not-approved-us", "approvalDetails": "Approved in Russia for cognitive impairment associated with organic brain disorders. Not approved by the FDA.", "mechanism": "Metabolized to cycloprolylglycine (CPG), which upregulates BDNF and NGF expression in the hippocampus and cortex. Additional actions include modulation of AMPA and NMDA receptor function, inhibition of glutamate excitotoxicity, and anxiolytic effects mediated through the cholinergic system. In-vivo potency is approximately 1000× that of piracetam by weight.", "primaryUses": [ "Cognitive impairment (Russian approval)", "Mild cognitive impairment research", "Community nootropic use" ], "typicalDose": { "range": "10–30", "unit": "mg", "frequency": "2–3 times daily", "route": "oral or sublingual", "notes": "Russian clinical dose: 10 mg twice daily, titrated to 30 mg/day if needed." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "Amelin AV, et al. \"[Noopept in the treatment of mild cognitive impairment in patients with stroke].\" Zh Nevrol Psikhiatr Im S S Korsakova, 2011;111(10 Pt 1):44-6. PMID: 22500312.", "pmid": "22500312" }, { "type": "pubmed", "citation": "Bochkarev VK, et al. \"[Clinical and electroencephalographic characteristic of noopept in patients with mild cognitive impairment of posttraumatic and vascular origin].\" Zh Nevrol Psikhiatr Im S S Korsakova, 2008;108(11):47-54. PMID: 19008801.", "pmid": "19008801" }, { "type": "pubmed", "citation": "Zainullina LF, et al. \"Drug with Neuroprotective Properties Noopept Does Not Stimulate Cell Proliferation.\" Bull Exp Biol Med, 2019;166(4):466-468. PMID: 30788746.", "pmid": "30788746" }, { "type": "pubmed", "citation": "Ostrovskaya RU, et al. \"The nootropic and neuroprotective proline-containing dipeptide noopept restores spatial memory and increases immunoreactivity to amyloid in an Alzheimer's disease model.\" J Psychopharmacol, 2007;21(6):611-9. PMID: 17092975.", "pmid": "17092975" }, { "type": "pubmed", "citation": "Gudasheva TA, et al. \"The major metabolite of dipeptide piracetam analogue GVS-111 in rat brain and its similarity to endogenous neuropeptide cyclo-L-prolylglycine.\" Eur J Drug Metab Pharmacokinet, 1997;22(3):245-52. PMID: 9358206.", "pmid": "9358206" }, { "type": "pubmed", "citation": "Ostrovskaya RU, et al. \"Noopept stimulates the expression of NGF and BDNF in rat hippocampus.\" Bull Exp Biol Med, 2008;146(3):334-7. PMID: 19240853.", "pmid": "19240853" }, { "type": "pubmed", "citation": "Ostrovskaya RU, et al. \"Proline-containing dipeptide GVS-111 retains nootropic activity after oral administration.\" Bull Exp Biol Med, 2001;132(4):959-62. PMID: 11782792.", "pmid": "11782792" }, { "type": "pubmed", "citation": "Ostrovskaia RU, et al. \"[Multicomponent antithrombotic effect of the neuroprotective prolyl dipeptide GVS-111 and its major metabolite cyclo-L-prolylglycine].\" Eksp Klin Farmakol, 2002;65(2):34-7. PMID: 12109290.", "pmid": "12109290" }, { "type": "pubmed", "citation": "Neznamov GG, Teleshova ES. \"Comparative studies of Noopept and piracetam in the treatment of patients with mild cognitive disorders in organic brain diseases of vascular and traumatic origin.\" Neurosci Behav Physiol, 2009;39:311-321. PMID: 19234797.", "pmid": "19234797" }, { "type": "pubmed", "citation": "Cohen PA, et al. \"Five Unapproved Drugs Found in Cognitive Enhancement Supplements.\" Neurol Clin Pract, 2021;11(3):e303-e307. PMID: 34484905.", "pmid": "34484905" } ], "interactionCoverage": "none-found", "related": [ "semax", "selank", "cerebrolysin" ], "lastReviewed": "2026-09-26", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": "Russia", "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptidomimetic", "moleculeClassBasis": "dipeptide ethyl ester" }, { "id": "npas3-peptide", "name": "NPAS3 Research Peptide", "aliases": [ "Neuronal PAS domain protein 3 fragment" ], "tier": "stub", "category": "cognitive", "subcategory": "bHLH-PAS transcription-factor-derived research peptide", "class": "Short peptide fragment derived from the NPAS3 neuronal transcription factor, which has been genetically linked to schizophrenia and cognitive phenotypes; examined in a limited preclinical literature as a research tool with no clinical therapeutic program.", "tagline": "A research-only peptide derived from the NPAS3 (neuronal PAS domain protein 3) basic helix-loop-helix PAS transcription factor. NPAS3 has been linked to schizophrenia and cognitive phenotypes in human genetic studies, but the peptide itself has no clinical development. No human trials, no established dosing, and no substantiated therapeutic use.", "oneLiner": "A short peptide fragment corresponding to a sequence within the bHLH-PAS transcription factor NPAS3. NPAS3 knockout in mice produces schizophrenia-like behavioral abnormalities and reduced adult hippocampal neurogenesis, and NPAS3 loss-of-function has been reported in rare human schizophrenia and intellectual disability pedigrees. Peptide fragments of NPAS3 have been examined in a small research literature primarily for their DNA-binding or protein-protein interaction properties. No therapeutic development; research-only.", "sequence": "Not standardized (sequence varies across preclinical reports)", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": null, "range": "Not characterized", "notes": "No pharmacokinetic data." }, "fdaStatus": "research-only", "approvalDetails": "Not FDA-approved. No registered clinical trials. No sponsoring developer. Listed in some grey-market research-peptide catalogs as a nootropic candidate; any such characterization is not supported by clinical evidence.", "mechanism": "NPAS3 is a member of the bHLH-PAS transcription factor family that dimerizes with ARNT (HIF-1β) and binds E-box elements to regulate genes involved in neurogenesis, circadian biology, and xenobiotic response. NPAS3-deficient mice show reduced adult hippocampal neurogenesis, altered social and prepulse inhibition behaviors, and changes in FGF signaling. Short NPAS3-derived peptides have primarily been used as research tools for studying bHLH-PAS dimerization or as epitopes for antibody generation, not as functional therapeutic mimetics.", "primaryUses": [ "Transcription-factor research (in vitro)", "Schizophrenia and neurodevelopmental genetics research (preclinical)" ], "typicalDose": { "range": "Not established", "unit": null, "frequency": null, "route": null, "notes": "⚠ No human dosing has ever been established. Any human use would be entirely experimental and unsupported." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Kamnasaran D, et al. \"Disruption of the neuronal PAS3 gene in a family affected with schizophrenia.\" J Med Genet, 2003;40:325-332. PMID: 12746393.", "pmid": "12746393" }, { "type": "pubmed", "citation": "Pieper AA, et al. \"The neuronal PAS domain protein 3 transcription factor controls FGF-mediated adult hippocampal neurogenesis in mice.\" Proc Natl Acad Sci USA, 2005;102:14052-14057. PMID: 16172381.", "pmid": "16172381" } ], "interactionCoverage": "unreviewed", "related": [ "brn2", "p21" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "octreotide", "name": "Octreotide", "aliases": [ "Sandostatin", "Bynfezia", "Mycapssa" ], "tier": "mid", "category": "growth-hormone", "subcategory": "somatostatin analog", "class": "A synthetic cyclic octapeptide somatostatin analog that binds SSTR2 and SSTR5 with high affinity, FDA-approved for acromegaly, carcinoid syndrome, and VIPoma.", "tagline": "The first-generation somatostatin analog (FDA-approved as Sandostatin, 1988) — the pharmacological counterweight to growth-hormone excess. Used for acromegaly, carcinoid syndrome, and VIPoma; now available in injectable, LAR-depot, and oral (Mycapssa, 2020) formulations.", "oneLiner": "A synthetic cyclic octapeptide analog of somatostatin, developed by Sandoz (now Novartis) and FDA-approved in 1988 as Sandostatin, with preferential binding to somatostatin receptor subtypes 2 and 5; the standard-of-care medical therapy for acromegaly and for hormonal symptom control in carcinoid syndrome and VIPoma, and an important reference compound in the growth-hormone-axis encyclopedia.", "sequence": "cyclic(D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-ol) (disulfide Cys2–Cys7)", "molecularFormula": "C49H66N10O10S2", "molecularWeight": 1019.24, "halfLife": { "value": 1.8, "unit": "hours", "range": "1.7 to 1.9 hours, against 1 to 3 minutes for natural somatostatin", "source": { "type": "label", "ref": "Sandostatin (octreotide acetate) injection prescribing information, sections 2, 5, 6 and 12.3 (DailyMed SPL version 23, effective July 22, 2026; read October 1, 2026)" } }, "fdaStatus": "approved", "approvalDetails": "Sandostatin injection, NDA 019667, approved October 21, 1988; Sandostatin LAR Depot, NDA 021008, November 25, 1998; Mycapssa delayed-release oral capsules, NDA 208232, June 26, 2020; Bynfezia Pen, NDA 213224, September 27, 2024 (Drugs@FDA, read October 1, 2026).", "mechanism": "Binds somatostatin receptor subtypes SSTR2 (high affinity) and SSTR5 (moderate affinity) on pituitary somatotrophs, carcinoid tumor cells, and VIPoma cells, inhibiting adenylyl cyclase, suppressing hormone secretion, and reducing tumor growth signaling. In acromegaly this reduces growth hormone and IGF-1; in carcinoid it reduces serotonin and flushing/diarrhea symptoms.", "primaryUses": [ "Acromegaly (adjunct or primary medical therapy)", "Carcinoid syndrome (flushing and diarrhea)", "VIPoma (watery diarrhea)", "Variceal bleeding (off-label hemostatic use)" ], "typicalDose": { "range": "50-500", "unit": "mcg", "frequency": "three times daily", "route": "subcutaneous or intravenous", "notes": "Sandostatin label for acromegaly: 50 mcg three times daily for the first two weeks, then 100 to 500 mcg three times daily. Carcinoid tumours 100 to 600 mcg a day and VIPomas 200 to 300 mcg a day, each in two to four doses during the first two weeks." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Sandostatin (octreotide acetate) injection prescribing information, sections 2, 5, 6 and 12.3 (DailyMed SPL version 23, effective July 22, 2026; read October 1, 2026)." }, { "type": "pubmed", "citation": "Goltstein LCMJ, et al. \"Standard of Care Versus Octreotide in Angiodysplasia-Related Bleeding (the OCEAN Study): A Multicenter Randomized Controlled Trial.\" Gastroenterology, 2024;166(4):690-703. PMID: 38158089.", "pmid": "38158089" }, { "type": "pubmed", "citation": "Currow DC, et al. \"Double-blind, placebo-controlled, randomized trial of octreotide in malignant bowel obstruction.\" J Pain Symptom Manage, 2015;49(5):814-21. PMID: 25462210.", "pmid": "25462210" }, { "type": "pubmed", "citation": "Gaujoux S, et al. \"Somatostatin Versus Octreotide for Prevention of Postoperative Pancreatic Fistula: The PREFIPS Randomized Clinical Trial: A FRENCH 007-ACHBT Study.\" Ann Surg, 2024;280(2):179-187. PMID: 38662619.", "pmid": "38662619" }, { "type": "pubmed", "citation": "Rinke A, et al. \"Placebo-Controlled, Double-Blind, Prospective, Randomized Study on the Effect of Octreotide LAR in the Control of Tumor Growth in Patients with Metastatic Neuroendocrine Midgut Tumors (PROMID): Results of Long-Term Survival.\" Neuroendocrinology, 2017;104(1):26-32. PMID: 26731483.", "pmid": "26731483" }, { "type": "pubmed", "citation": "Rinke A, et al. \"Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group.\" J Clin Oncol, 2009;27(28):4656-63. PMID: 19704057.", "pmid": "19704057" }, { "type": "pubmed", "citation": "Fan M, et al. \"Octreotide and Octreotide-derived delivery systems.\" J Drug Target, 2023;31(6):569-584. PMID: 37211679.", "pmid": "37211679" }, { "type": "pubmed", "citation": "Cavallin M, et al. \"Terlipressin plus albumin versus midodrine and octreotide plus albumin in the treatment of hepatorenal syndrome: A randomized trial.\" Hepatology, 2015;62(2):567-74. PMID: 25644760.", "pmid": "25644760" } ], "interactionCoverage": "partial", "related": [ "lanreotide", "somatropin", "tesamorelin" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "omiganan", "name": "Omiganan", "aliases": [ "MBI-226", "MX-594AN", "CLS001", "Omiganan pentahydrochloride", "Omigard" ], "tier": "full", "category": "healing", "subcategory": "Indolicidin-derived antimicrobial peptide", "class": "A 12-amino-acid synthetic analog of bovine indolicidin (a tryptophan-rich cathelicidin antimicrobial peptide) developed as a topical gel, first to prevent catheter-site infection and then for rosacea and other skin conditions. Two catheter phase 3 trials missed their primary endpoints; of two rosacea phase 3 trials, one met its co-primary endpoints and one did not. Never approved.", "tagline": "An indolicidin-derived cationic antimicrobial peptide developed as a topical gel over two decades. Its catheter-infection phase 3 trials (completed 2003, and CLIRS, 2005–2008) missed their primary endpoints, and its 2015–2017 rosacea phase 3 programme produced one positive and one negative trial. Never approved.", "oneLiner": "A 12-residue synthetic analog of bovine indolicidin, a tryptophan-rich cathelicidin from cow neutrophils (sequence ILRWPWWPWRRK-NH2; five positive charges, four tryptophans). Micrologix (later Migenix) and Fujisawa tested a 1% gel against 10% povidone-iodine at central venous catheter sites in a phase 3 trial of 1,407 patients completed in February 2003: it missed its primary endpoint (catheter-related bloodstream infection) while reducing local catheter-site infection and colonisation. Cadence Pharmaceuticals licensed it as Omigard in 2004; its confirmatory CLIRS trial (NCT00231153, 1,859 patients, 2005–2008) missed its primary endpoint of local catheter-site infection (6.3% vs 8.6%, P=0.082), and catheter development ended in 2009. Cutanea Life Sciences then developed it for rosacea as CLS001: of two phase 3 trials in severe papulopustular rosacea (2015–2017), one (463 patients) met both co-primary endpoints and one (263 patients) met neither. Phase 2 trials in atopic dermatitis, seborrhoeic dermatitis and HPV-induced genital lesions showed microbiome or viral-load effects without clinical benefit. Never approved.", "sequence": "Ile-Leu-Arg-Trp-Pro-Trp-Trp-Pro-Trp-Arg-Arg-Lys (amidated C-terminus)", "molecularFormula": "C90H127N27O12", "molecularWeight": 1779.1, "halfLife": { "value": null, "unit": null, "range": "Not established (topical gel only)", "notes": "Developed only as a topical gel; no published human pharmacokinetic study was found in PubMed (searched September 30, 2026)." }, "fdaStatus": "discontinued", "approvalDetails": "Not FDA-approved: Drugs@FDA holds no application for omiganan or Omigard (read September 30, 2026), and EMA's register of centrally authorised medicines has no entry. Catheter-site phase 3 trials: Micrologix/Fujisawa (1,407 patients, completed February 2003; primary endpoint missed) and Cadence's CLIRS (NCT00231153; primary endpoint missed, P=0.082); catheter development ended in 2009. Rosacea phase 3 (Cutanea Life Sciences, now listed under Maruho, 2015–2017): NCT02547441 met both co-primary endpoints, NCT02576860 met neither.", "mechanism": "Cationic amphipathic antimicrobial peptide. Its four tryptophans and five positive charges drive partitioning into negatively charged, bacteria-like membranes, roughly an order of magnitude more readily than into neutral, mammalian-like membranes, with membrane saturation at low lipid-to-peptide ratios. Bactericidal and fungicidal against gram-positive and gram-negative bacteria and yeasts, with potency largely unaffected by methicillin, vancomycin or azole resistance. In human immune cells it amplifies interferon-alpha responses to endosomal toll-like receptor ligands (TLR3, 7, 8, 9), as LL-37 does, and it enhanced imiquimod-induced skin inflammation in volunteers.", "primaryUses": [ "Prevention of catheter-site infection (phase 3 trials completed 2003 and 2008; primary endpoints missed)", "Papulopustular rosacea (two phase 3 trials, 2015–2017: one met its co-primary endpoints, one did not)", "Atopic dermatitis, seborrhoeic dermatitis and HPV-induced genital lesions (phase 2; no clinical benefit shown)", "Antimicrobial peptide drug-development case study" ], "typicalDose": { "range": "Not established (investigational only)", "unit": null, "frequency": null, "route": "topical", "notes": "Catheter trials: 1% gel applied around the insertion site after catheter placement and at each dressing change (every 3 days in CLIRS). Rosacea phase 3: CLS001 gel once daily for 12 weeks. Phase 2 dermatology trials: 1% to 2.5% gels once or twice daily for 4 to 12 weeks. No approved product." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Niemeyer-van der Kolk T, et al. \"Topical antimicrobial peptide omiganan recovers cutaneous dysbiosis but does not improve clinical symptoms in patients with mild to moderate atopic dermatitis in a phase 2 randomized controlled trial.\" J Am Acad Dermatol, 2022;86(4):854-862. PMID: 33010325.", "pmid": "33010325" }, { "type": "pubmed", "citation": "Niemeyer-van der Kolk T, et al. \"Pharmacodynamic Effects of Topical Omiganan in Patients With Mild to Moderate Atopic Dermatitis in a Randomized, Placebo-Controlled, Phase II Trial.\" Clin Transl Sci, 2020;13(5):994-1003. PMID: 32315497.", "pmid": "32315497" }, { "type": "pubmed", "citation": "Rousel J, et al. \"Treatment with the Topical Antimicrobial Peptide Omiganan in Mild-to-Moderate Facial Seborrheic Dermatitis versus Ketoconazole and Placebo: Results of a Randomized Controlled Proof-of-Concept Trial.\" Int J Mol Sci, 2023;24(18). PMID: 37762625.", "pmid": "37762625" }, { "type": "pubmed", "citation": "Rijsbergen M, et al. \"Results of phase 2 trials exploring the safety and efficacy of omiganan in patients with human papillomavirus-induced genital lesions.\" Br J Clin Pharmacol, 2020;86(11):2133-2143. PMID: 31755993.", "pmid": "31755993" }, { "type": "pubmed", "citation": "Niemeyer-van der Kolk T, et al. \"Omiganan Enhances Imiquimod-Induced Inflammatory Responses in Skin of Healthy Volunteers.\" Clin Transl Sci, 2020;13(3):573-579. PMID: 32043302.", "pmid": "32043302" }, { "type": "pubmed", "citation": "Grievink HW, et al. \"Antimicrobial Peptide Omiganan Enhances Interferon Responses to Endosomal Toll-Like Receptor Ligands in Human Peripheral Blood Mononuclear Cells.\" Clin Transl Sci, 2020;13(5):891-895. PMID: 32314872.", "pmid": "32314872" }, { "type": "pubmed", "citation": "Isaacson RE. \"MBI-226. Micrologix/Fujisawa.\" Curr Opin Investig Drugs, 2003;4(8):999-1003. PMID: 14508884.", "pmid": "14508884" }, { "type": "pubmed", "citation": "Melo MN, et al. \"Omiganan pentahydrochloride in the front line of clinical applications of antimicrobial peptides.\" Recent Pat Antiinfect Drug Discov, 2006;1(2):201-7. PMID: 18221145.", "pmid": "18221145" }, { "type": "pubmed", "citation": "Sader HS, et al. \"Omiganan pentahydrochloride (MBI 226), a topical 12-amino-acid cationic peptide: spectrum of antimicrobial activity and measurements of bactericidal activity.\" Antimicrob Agents Chemother, 2004;48(8):3112-8. PMID: 15273128.", "pmid": "15273128" }, { "type": "pubmed", "citation": "Fritsche TR, et al. \"Antimicrobial activity of omiganan pentahydrochloride tested against contemporary bacterial pathogens commonly responsible for catheter-associated infections.\" J Antimicrob Chemother, 2008;61(5):1092-8. PMID: 18310135.", "pmid": "18310135" }, { "type": "pubmed", "citation": "Fritsche TR, et al. \"In vitro activity of omiganan pentahydrochloride tested against vancomycin-tolerant, -intermediate, and -resistant Staphylococcus aureus.\" Diagn Microbiol Infect Dis, 2008;60(4):399-403. PMID: 18178361.", "pmid": "18178361" }, { "type": "pubmed", "citation": "Fritsche TR, et al. \"Antimicrobial activity of omiganan pentahydrochloride against contemporary fungal pathogens responsible for catheter-associated infections.\" Antimicrob Agents Chemother, 2008;52(3):1187-9. PMID: 18180345.", "pmid": "18180345" }, { "type": "pubmed", "citation": "Żyrek D, et al. \"The Antimicrobial Activity of Omiganan Alone and In Combination against Candida Isolated from Vulvovaginal Candidiasis and Bloodstream Infections.\" Antibiotics (Basel), 2021;10(8). PMID: 34439051.", "pmid": "34439051" }, { "type": "pubmed", "citation": "Melo MN, et al. \"Omiganan interaction with bacterial membranes and cell wall models. Assigning a biological role to saturation.\" Biochim Biophys Acta, 2007;1768(5):1277-90. PMID: 17383609.", "pmid": "17383609" }, { "type": "pubmed", "citation": "Ng SMS, et al. \"Preliminary investigations into developing all-D Omiganan for treating Mupirocin-resistant MRSA skin infections.\" Chem Biol Drug Des, 2017;90(6):1155-1160. PMID: 28581672.", "pmid": "28581672" }, { "type": "pubmed", "citation": "Rubinchik E, et al. \"Antimicrobial and antifungal activities of a novel cationic antimicrobial peptide, omiganan, in experimental skin colonisation models.\" Int J Antimicrob Agents, 2009;34(5):457-61. PMID: 19524411.", "pmid": "19524411" }, { "type": "pubmed", "citation": "Lorenzi T, et al. \"Effect of omiganan on colonic anastomosis healing in a rat model of peritonitis.\" Am J Transl Res, 2017;9(7):3374-3386. PMID: 28804554.", "pmid": "28804554" }, { "type": "pubmed", "citation": "Javia A, et al. \"Liposomes encapsulating novel antimicrobial peptide Omiganan: Characterization and its pharmacodynamic evaluation in atopic dermatitis and psoriasis mice model.\" Int J Pharm, 2022;624:122045. PMID: 35878872.", "pmid": "35878872" }, { "type": "clinical-trial", "citation": "Cadence Pharmaceuticals. \"A Phase 3, Multicenter, Randomized, Evaluation Committee-Blinded Study to Assess the Efficacy of Topical Omiganan 1% Gel in Preventing Local Catheter Site Infections/Colonization in Patients Undergoing Central Venous Catheterization\" (CLIRS). ClinicalTrials.gov NCT00231153; completed July 2008; results read September 30, 2026." }, { "type": "clinical-trial", "citation": "Maruho Co., Ltd. (Cutanea Life Sciences). Phase 3 trial of once-daily CLS001 (omiganan) gel versus vehicle for 12 weeks in papulopustular rosacea, with an open-label safety extension. ClinicalTrials.gov NCT02547441; primary completion July 5, 2017; results read September 30, 2026." }, { "type": "clinical-trial", "citation": "Maruho Co., Ltd. (Cutanea Life Sciences). Phase 3 trial of once-daily CLS001 (omiganan) gel versus vehicle for 12 weeks in papulopustular rosacea. ClinicalTrials.gov NCT02576860; primary completion February 27, 2017; results read September 30, 2026." }, { "type": "clinical-trial", "citation": "Maruho Co., Ltd. (Cutanea Life Sciences). Phase 3 open-label extension of omiganan topical gel in rosacea (long-term safety). ClinicalTrials.gov NCT02576847; primary completion July 14, 2017; results read September 30, 2026." }, { "type": "news-release", "citation": "Cadence Pharmaceuticals. \"Cadence Pharmaceuticals, Inc. Announces Plan to Increase Number of Patients to Be Enrolled in Its Phase III Clinical Trial of Omigard.\" Press release, April 30, 2007 (describes the first phase 3 trial: 1,407 patients, 27 US centres, completed February 2003). Read September 30, 2026." }, { "type": "fda", "citation": "FDA. Drugs@FDA (openFDA): no application for omiganan or Omigard. Read September 30, 2026." }, { "type": "other", "citation": "European Medicines Agency. Medicines register (centrally authorised human medicines): no entry for omiganan. Read September 30, 2026." } ], "interactionCoverage": "studied", "related": [ "ll-37", "pexiganan" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "A discontinued drug: S0's own examples include discontinued drugs." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "A discontinued drug: S0's own examples include discontinued drugs." } ], "moleculeClass": "peptide" }, { "id": "orexin-a", "name": "Orexin-A", "aliases": [ "Hypocretin-1", "OX-A", "HCRT-1" ], "tier": "mid", "category": "cognitive", "subcategory": "Endogenous neuropeptide", "class": "Orexin-A is the hypothalamic wakefulness peptide whose loss causes narcolepsy. The orexin system is the target of the blockbuster insomnia drugs suvorexant (Belsomra) and lemborexant (Dayvigo).", "tagline": "The hypothalamic wakefulness peptide — loss of orexin neurons causes narcolepsy, and blocking its receptors produced the blockbuster insomnia drugs suvorexant and lemborexant.", "oneLiner": "A 33-amino-acid peptide produced exclusively by ~70,000 neurons in the lateral hypothalamus that maintains wakefulness, stabilizes sleep-wake transitions, and regulates appetite — its deficiency is the definitive cause of narcolepsy type 1.", "sequence": "QPLPDCCRQKTCSCRLYELLHGAGNHAAGILTL-amide (two disulfide bonds)", "molecularFormula": "C152H243N47O44S4", "molecularWeight": 3562.1, "halfLife": { "value": null, "unit": null, "range": "not reported in the sources read", "source": { "type": "none", "note": "searched PubMed on October 1, 2026; no human half-life figure in the sources read" } }, "fdaStatus": "research-only", "approvalDetails": "Not approved as a drug; no application appears in Drugs@FDA (read October 1, 2026). Dual orexin receptor antagonists are approved for insomnia, and orexin receptor 2 agonists for narcolepsy are in trials.", "mechanism": "Binds OX1R (selective) and OX2R (non-selective) — both Gq-coupled GPCRs that depolarize target neurons. Orexin neurons project widely to the locus coeruleus, dorsal raphe, tuberomammillary nucleus, and basal forebrain, stabilizing the 'wake' state of the sleep-wake flip-flop switch. Loss of orexin neurons (autoimmune destruction) causes narcolepsy type 1 with cataplexy.", "primaryUses": [ "Endogenous wakefulness stabilization", "CSF orexin-A measurement as diagnostic biomarker for narcolepsy type 1 (<110 pg/mL)", "Drug target: DORAs for insomnia; orexin agonists in development for narcolepsy" ], "typicalDose": { "range": null, "unit": null, "frequency": null, "route": null, "notes": "Not a medicine. The narcolepsy trials give small-molecule receptor 2 agonists by mouth, not the peptide." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Dauvilliers Y, et al. \"Oral Orexin Receptor 2 Agonist in Narcolepsy Type 1.\" N Engl J Med, 2023;389(4):309-321. PMID: 37494485.", "pmid": "37494485" }, { "type": "pubmed", "citation": "Dauvilliers Y, et al. \"Oveporexton, an Oral Orexin Receptor 2-Selective Agonist, in Narcolepsy Type 1.\" N Engl J Med, 2025;392(19):1905-1916. PMID: 40367374.", "pmid": "40367374" }, { "type": "pubmed", "citation": "Kanbayashi T, et al. \"Hypocretin-1 (orexin-A) levels in human lumbar CSF in different age groups: infants to elderly persons.\" Sleep, 2002;25(3):337-9. PMID: 12003164.", "pmid": "12003164" }, { "type": "pubmed", "citation": "Boddum K, et al. \"Cerebrospinal Fluid Hypocretin-1 (Orexin-A) Level Fluctuates with Season and Correlates with Day Length.\" PLoS One, 2016;11(3):e0151288. PMID: 27008404.", "pmid": "27008404" }, { "type": "pubmed", "citation": "Dauvilliers Y, et al. \"Daridorexant, a New Dual Orexin Receptor Antagonist to Treat Insomnia Disorder.\" Ann Neurol, 2020;87(3):347-356. PMID: 31953863.", "pmid": "31953863" }, { "type": "pubmed", "citation": "de Lecea L, et al. \"The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity.\" Proc Natl Acad Sci U S A, 1998;95(1):322-7. PMID: 9419374.", "pmid": "9419374" }, { "type": "pubmed", "citation": "Mahoney CE, et al. \"The neurobiological basis of narcolepsy.\" Nat Rev Neurosci, 2019;20(2):83-93. PMID: 30546103.", "pmid": "30546103" }, { "type": "pubmed", "citation": "Sakurai T, et al. \"Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior.\" Cell, 1998;92(4):573-85. PMID: 9491897.", "pmid": "9491897" } ], "interactionCoverage": "unreviewed", "related": [ "orexin-b", "neuropeptide-y", "ghrelin", "dsip" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-21", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "orexin-b", "name": "Orexin-B", "aliases": [ "Hypocretin-2", "OX-B", "HCRT-2" ], "tier": "stub", "category": "cognitive", "subcategory": "Endogenous neuropeptide", "class": "Orexin-B is the second orexin peptide, co-expressed with Orexin-A from the same precursor, with preferential activity at the OX2 receptor that dominates wakefulness maintenance.", "tagline": "The second orexin isoform — a 28-amino-acid peptide that preferentially activates the OX2 receptor most critical for maintaining wakefulness.", "oneLiner": "A 28-amino-acid linear peptide co-produced with Orexin-A from prepro-orexin that selectively activates OX2R and is less stable than Orexin-A due to its lack of disulfide bonds.", "sequence": "RSGPPGLQGRLQRLLQASGNHAAGILTM-amide", "molecularFormula": "C130H209N43O36", "molecularWeight": 2937.4, "halfLife": { "value": 5, "unit": "minutes", "range": "3-8 minutes", "notes": "Significantly shorter half-life than Orexin-A (~5 min vs ~30 min) because it lacks disulfide bonds." }, "fdaStatus": "research-only", "approvalDetails": "Not approved as a drug. Same receptor targets as Orexin-A. OX2R-selective agonists in development may have advantages for narcolepsy treatment.", "mechanism": "Binds OX2R with high affinity and OX1R with ~10-fold lower affinity. OX2R is the dominant receptor for wakefulness — OX2R knockout mice exhibit severe narcolepsy while OX1R knockout mice show milder sleep fragmentation.", "primaryUses": [ "Endogenous wakefulness maintenance (OX2R-mediated)", "Research tool for dissecting OX1R vs OX2R contributions to sleep/wake regulation" ], "typicalDose": { "range": "N/A", "unit": "N/A", "frequency": "N/A", "route": "endogenous", "notes": "Not used therapeutically. CSF Orexin-B is not routinely measured clinically." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Sakurai T, et al. \"Orexins and orexin receptors.\" Cell. 1998;92(4):573-585. PMID: 9491897.", "pmid": "9491897" }, { "type": "review", "citation": "Mieda M. \"The roles of orexins in sleep/wake regulation.\" Neurosci Res. 2017;118:56-65. PMID: 28526554.", "pmid": "28526554" } ], "interactionCoverage": "unreviewed", "related": [ "orexin-a", "neuropeptide-y", "dsip" ], "lastReviewed": "2026-04-21", "publishedAt": "2026-04-21", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "orforglipron", "name": "Orforglipron", "aliases": [ "LY3502970", "OWL833" ], "tier": "full", "category": "metabolic", "subcategory": "oral small-molecule GLP-1 agonist", "class": "Investigational non-peptide, oral small-molecule GLP-1 receptor agonist.", "tagline": "Not a peptide: an oral small-molecule GLP-1 receptor agonist, FDA-approved on April 1, 2026 as Foundayo for weight management; at its top dose it cut weight 11.2% over 72 weeks in ATTAIN-1, against 2.1% on placebo.", "oneLiner": "An orally bioavailable, non-peptide small molecule (C48H48F2N10O5) that activates the GLP-1 receptor as a G-protein-biased partial agonist through a pocket GLP-1 does not use; active only at the primate receptor.", "sequence": null, "molecularFormula": "C48H48F2N10O5", "molecularWeight": 883.0, "halfLife": { "value": 39, "unit": "hours", "range": "about 29–49 hours after an oral dose (label)", "notes": "Foundayo label; steady state after about 1 week of daily dosing. The value is the midpoint of the labelled range. Phase 1 measured 24.6–35.3 h after single doses and 48.1–67.5 h after four weeks." }, "fdaStatus": "approved", "approvalDetails": "FDA-approved April 1, 2026 as Foundayo (Eli Lilly, in-licensed from Chugai Pharmaceutical; NDA 220934) for chronic weight management in adults with obesity, or overweight with at least one weight-related comorbidity, alongside a reduced-calorie diet and increased physical activity. The first new molecular entity approved under the FDA Commissioner's National Priority Voucher pilot programme — cleared 50 days after filing, against a PDUFA date of January 20, 2027. Approval rests on the Phase 3 ATTAIN programme (ATTAIN-1, n=3,127 without diabetes; ATTAIN-2, n=1,613 with type 2 diabetes). Carries a boxed warning for thyroid C-cell tumours, including medullary thyroid carcinoma. A small molecule, not a peptide — it is catalogued here because it is persistently miscategorised as one. Type 2 diabetes, obstructive sleep apnoea and hypertension indications remain under study.", "mechanism": "Non-peptide agonist at the GLP-1 receptor: it binds an upper pocket formed by the extracellular domain, extracellular loop 2 and transmembrane helices 1, 2, 3 and 7, acting as a partial agonist biased to G-protein signalling; its dependence on the primate-specific Trp33 makes it inactive in rats and mice. Effects in people are the class's: lower glucose and body weight with gastrointestinal side effects during dose escalation.", "primaryUses": [ "Obesity — Phase 3", "Type 2 diabetes — Phase 3" ], "typicalDose": { "range": "0.8–17.2", "unit": "mg", "frequency": "once daily", "route": "oral", "notes": "Foundayo label: 0.8 mg, then 2.5 mg and 5.5 mg at intervals of at least 30 days, optionally 9, 14.5 or 17.2 mg (maximum). Trials used capsules of 3, 6, 12 and 36 mg, bioequivalent to tablets of 2.5, 5.5, 9 and 17.2 mg." }, "evidenceLevel": "medium", "sources": [ { "type": "fda-pi", "citation": "Foundayo (orforglipron) tablets Prescribing Information. Eli Lilly and Company (DailyMed version of 2026-08-13, read 2026-09-28)." }, { "type": "fda-pi", "citation": "US FDA, Drugs@FDA: Foundayo (orforglipron) NDA 220934, approved April 1, 2026 (read 2026-09-28)." }, { "type": "Human", "citation": "Wharton S, et al. \"Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment.\" N Engl J Med, 2025;393(18):1796-1806. PMID: 40960239.", "pmid": "40960239" }, { "type": "Human", "citation": "Horn DB, et al. \"Orforglipron, an oral small-molecule GLP-1 receptor agonist, for the treatment of obesity in people with type 2 diabetes (ATTAIN-2): a phase 3, double-blind, randomised, multicentre, placebo-controlled trial.\" Lancet, 2026;406(10522):2927-2944. PMID: 41275875.", "pmid": "41275875" }, { "type": "Human", "citation": "Aronne LJ, et al. \"Orforglipron for maintenance of body weight reduction: the double-blind, randomized phase 3b ATTAIN-MAINTAIN trial.\" Nat Med, 2026;32(7):2679-2687. PMID: 42120723.", "pmid": "42120723" }, { "type": "Human", "citation": "Wharton S, et al. \"Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity.\" N Engl J Med, 2023;389(10):877-888. PMID: 37351564.", "pmid": "37351564" }, { "type": "Human", "citation": "Rosenstock J, et al. \"Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist, in Early Type 2 Diabetes.\" N Engl J Med, 2025;393(11):1065-1076. PMID: 40544435.", "pmid": "40544435" }, { "type": "Human", "citation": "Rosenstock J, et al. \"Efficacy and safety of once-daily oral orforglipron compared with oral semaglutide in adults with type 2 diabetes (ACHIEVE-3): a multinational, multicentre, non-inferiority, open-label, randomised, phase 3 trial.\" Lancet, 2026;407(10534):1147-1160. PMID: 41765029.", "pmid": "41765029" }, { "type": "Human", "citation": "Welch M, et al. \"Orforglipron compared with dapagliflozin in adults with type 2 diabetes and inadequate glycaemic control with metformin (ACHIEVE-2): a multicentre, randomised, non-inferiority, open-label, phase 3 trial.\" Lancet, 2026;408(10550):125-140. PMID: 42259339.", "pmid": "42259339" }, { "type": "Human", "citation": "Giorgino F, et al. \"Orforglipron Added to Titrated Insulin Glargine in Type 2 Diabetes: The ACHIEVE-5 Randomized Clinical Trial.\" JAMA, 2026;336(5):389-399. PMID: 42251769.", "pmid": "42251769" }, { "type": "Human", "citation": "Wharton S, et al. \"Hepatic Safety of Orforglipron in Adults With Obesity or Overweight and/or Type 2 Diabetes: A Pooled Analysis of the Orforglipron Phase 3 Clinical Trials.\" Diabetes Obes Metab, 2026;28(9):8347-8358. PMID: 42338042.", "pmid": "42338042" }, { "type": "Human", "citation": "Ma X, et al. \"Pharmacokinetic Bioequivalence of Orforglipron Tablets and Capsules in Healthy Participants With Obesity or Overweight.\" Diabetes Obes Metab, 2026;28(7):5803-5809. PMID: 41994902.", "pmid": "41994902" }, { "type": "Human", "citation": "Morse BL, et al. \"Disposition and Absolute Bioavailability of Orally Administered Orforglipron in Healthy Participants.\" Clin Pharmacol Drug Dev, 2026;15(1):e1594. PMID: 40888509.", "pmid": "40888509" }, { "type": "Human", "citation": "Pratt E, et al. \"Orforglipron (LY3502970), a novel, oral non-peptide glucagon-like peptide-1 receptor agonist: A Phase 1a, blinded, placebo-controlled, randomized, single- and multiple-ascending-dose study in healthy participants.\" Diabetes Obes Metab, 2023;25(9):2634-2641. PMID: 37344954.", "pmid": "37344954" }, { "type": "In Vitro", "citation": "Kawai T, et al. \"Structural basis for GLP-1 receptor activation by LY3502970, an orally active nonpeptide agonist.\" Proc Natl Acad Sci U S A, 2020;117(47):29959-29967. PMID: 33177239.", "pmid": "33177239" }, { "type": "Review", "citation": "Shirley M. \"Orforglipron: First Approval.\" Drugs, 2026;86(10):1735-1745. PMID: 42479349.", "pmid": "42479349" } ], "interactionCoverage": "label", "related": [ "semaglutide", "tirzepatide" ], "lastReviewed": "2026-09-28", "publishedAt": "2026-04-18", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "small-molecule", "moleculeClassBasis": "small-molecule" }, { "id": "ovagen", "name": "Ovagen", "aliases": [ "Glu-Asp-Leu", "EDL tripeptide" ], "tier": "stub", "category": "longevity", "subcategory": "Khavinson short-chain bioregulator (hepatic / reproductive)", "class": "A synthetic short tripeptide developed by the Khavinson group as a \"hepatic / reproductive-tissue bioregulator\".", "tagline": "A Khavinson tripeptide proposed to support hepatocyte function and reproductive-tissue aging; evidence is Russian-language and pre-clinical.", "oneLiner": "A Khavinson-group short tripeptide (Glu-Asp-Leu) marketed as a hepatic bioregulator with proposed effects on hepatocyte regeneration and on reproductive-tissue aging in the Russian clinical bioregulator literature.", "sequence": "Glu-Asp-Leu", "molecularFormula": "C15H25N3O8", "molecularWeight": 375.37, "halfLife": { "value": null, "unit": null, "range": "undetermined", "notes": "Pharmacokinetics not characterized in Western-standard studies." }, "fdaStatus": "research-only", "approvalDetails": "Not FDA-approved. Marketed in Russia as a bioregulator supplement.", "mechanism": "Proposed to bind promoter regions in hepatocytes and reproductive-tissue cells to support tissue-specific gene expression. Animal studies from the Khavinson group report improved hepatocyte function after induced liver injury.", "primaryUses": [ "Investigational hepatic support (Russian literature)", "Research into reproductive-tissue aging" ], "typicalDose": { "range": "not established", "unit": null, "frequency": "not established", "route": "oral (capsule)", "notes": "Typical supplement protocols use 10 mg daily for 10–20 days." }, "evidenceLevel": "low", "sources": [ { "type": "review", "citation": "Khavinson VK, Malinin VV. \"Gerontological aspects of genome peptide regulation.\" Karger AG, Basel, 2005." }, { "type": "pubmed", "citation": "Khavinson VK, Kuznik BI, Ryzhak GA. \"Peptide bioregulators: a new class of geroprotectors. Message 1. Results of experimental studies.\" Adv Gerontol, 2012;25:696-708. PMID: 23734519.", "pmid": "23734519" } ], "interactionCoverage": "unreviewed", "related": [ "livagen", "epithalon", "cortagen" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "oxytocin", "name": "Oxytocin", "aliases": [ "Pitocin", "Syntocinon", "OXT" ], "tier": "mid", "category": "sexual-health", "subcategory": "neuropeptide hormone", "class": "Endogenous nonapeptide hormone and neuromodulator synthesized in the hypothalamus.", "tagline": "An endogenous nine-amino-acid hormone with roles in labor, lactation, and social-affiliative behavior; also explored off-label for social/anxiety research.", "oneLiner": "A cyclic nine-amino-acid peptide synthesized in the paraventricular and supraoptic nuclei of the hypothalamus that acts peripherally on uterine/mammary tissue and centrally on social cognition circuits.", "sequence": "CYIQNCPLG-NH2 (disulfide bridge Cys1–Cys6, C-terminal amide)", "molecularFormula": "C43H66N12O12S2", "molecularWeight": 1007.2, "halfLife": { "value": 3, "unit": "minutes", "range": "about 1 to 6 minutes (plasma), shorter in late pregnancy and lactation", "notes": "Pitocin label: plasma half-life about 1-6 minutes, shorter in late pregnancy and lactation; cleared mainly by the kidney and liver.", "source": { "type": "label", "ref": "Pitocin prescribing information, section 12.3 (DailyMed version 15, effective May 5, 2026; read September 30, 2026)" } }, "fdaStatus": "approved", "approvalDetails": "FDA: PITOCIN (oxytocin injection), NDA 018261, current application approved November 19, 1980 (Drugs@FDA), for antepartum and postpartum use; label effective May 5, 2026. Intranasal oxytocin is not FDA-approved in the US.", "mechanism": "Agonist at the oxytocin receptor (OXTR), a Gq-coupled GPCR. Peripheral effects include uterine smooth muscle contraction and milk ejection. Central effects — studied via intranasal administration in research — include modulation of amygdala activity, social salience, trust, and pair-bonding behavior. Central effects are inconsistently replicated.", "primaryUses": [ "Labor induction (FDA-approved)", "Postpartum hemorrhage prevention (FDA-approved)", "Autism spectrum disorder (investigational)", "Social anxiety / PTSD (research)" ], "typicalDose": { "range": "varies by indication", "unit": "", "frequency": "varies", "route": "IV (labor) / intranasal (research)", "notes": "Research intranasal dosing often 24 IU single-dose. Community use carries significant cardiovascular and water-intoxication risks." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Par Health. PITOCIN (oxytocin injection), US prescribing information: contraindications, adverse reactions and clinical pharmacology (plasma half-life about 1 to 6 minutes). DailyMed version effective May 5, 2026; read September 30, 2026." }, { "type": "pubmed", "citation": "Widmer M, et al. \"Heat-Stable Carbetocin versus Oxytocin to Prevent Hemorrhage after Vaginal Birth.\" N Engl J Med, 2018;379(8):743-752. PMID: 29949473.", "pmid": "29949473" }, { "type": "pubmed", "citation": "Bor P, et al. \"Continuation versus discontinuation of oxytocin infusion during the active phase of labour: a randomised controlled trial.\" BJOG, 2016;123(1):129-35. PMID: 26309128.", "pmid": "26309128" }, { "type": "pubmed", "citation": "Aboshama RA, et al. \"High dose vs. low dose oxytocin for labor augmentation: a systematic review and meta-analysis of randomized controlled trials.\" J Perinat Med, 2021;49(2):178-190. PMID: 32950965.", "pmid": "32950965" }, { "type": "pubmed", "citation": "Hollander E, et al. \"Intranasal oxytocin versus placebo for hyperphagia and repetitive behaviors in children with Prader-Willi Syndrome: A randomized controlled pilot trial.\" J Psychiatr Res, 2021;137:643-651. PMID: 33190843.", "pmid": "33190843" }, { "type": "pubmed", "citation": "Moerkerke M, et al. \"Impact of chronic intranasal oxytocin administration on face expression processing in autistic children: a randomized controlled trial using fMRI.\" Mol Autism, 2024;15(1):53. PMID: 39709442.", "pmid": "39709442" }, { "type": "fda", "citation": "FDA. Drugs@FDA (openFDA): PITOCIN, NDA 018261, current application approved November 19, 1980. Read September 30, 2026." } ], "interactionCoverage": "label", "related": [ "carbetocin", "atosiban", "pt-141" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-18", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "p21", "name": "P21", "aliases": [ "Cerebrolysin-derived peptide 21", "Cognitive enhancer peptide-21" ], "tier": "stub", "category": "cognitive", "subcategory": "CNTF-mimetic peptide fragment", "class": "A short peptide mimetic derived from a sequence in ciliary neurotrophic factor (CNTF), investigated as a cognitive enhancer and neurogenic agent in preclinical models.", "tagline": "A CNTF-derived research peptide (Institute for Basic Research, New York) that crosses the blood-brain barrier and stimulates hippocampal neurogenesis in rodent models of Alzheimer disease, Down syndrome, and aging. Not FDA-approved; not commercially marketed; research-only with no human trials to date.", "oneLiner": "A peptidomimetic derived from a 21-amino-acid region of the human ciliary neurotrophic factor (CNTF) D1 domain. Developed by Iqbal and colleagues at the New York State Institute for Basic Research in Developmental Disabilities as a small neurotrophic peptide candidate for age-related cognitive decline, Alzheimer disease, and Down syndrome; shown in rodent studies to enhance adult hippocampal neurogenesis, reduce tau phosphorylation, and improve spatial learning. No human clinical data; peptide remains a research tool.", "sequence": "Ac-DGGLAG-NH2 (hexapeptide active core reported)", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": "hours", "range": "Not established in human studies", "notes": "Reported to cross the blood-brain barrier after peripheral administration in rodents; pharmacokinetic parameters not formally characterized." }, "fdaStatus": "research-only", "approvalDetails": "Not FDA-approved. No human clinical trials registered on ClinicalTrials.gov. Sold informally in the research-chemical / nootropic grey market, often mislabeled or with questionable provenance. Any human use would be unapproved and unregulated.", "mechanism": "Reported to bind the leukemia inhibitory factor receptor beta (LIFRβ) / gp130 complex — the shared CNTF signaling receptor — activating downstream JAK/STAT3 and MAPK signaling associated with neuronal survival and adult hippocampal neurogenesis. In rodent models, P21 has been reported to reduce tau hyperphosphorylation, improve hippocampal-dependent memory performance, and reverse cognitive deficits in APP/PS1 and 3xTg-AD Alzheimer models. Mechanism remains incompletely characterized and receptor binding data are derived from a small number of preclinical reports from a single research group.", "primaryUses": [ "Cognitive enhancement research (preclinical only)", "Alzheimer disease model studies (rodent)", "Down syndrome cognitive deficit models (rodent)" ], "typicalDose": { "range": "Not established for human use", "unit": null, "frequency": null, "route": null, "notes": "⚠ No human dosing has been established. Rodent studies have used 25–500 μg/kg ranges. Any human use would be entirely off-label, unapproved, and unsupported by any clinical evidence." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Bolognin S, et al. \"An experimental rat model of sporadic Alzheimer's disease and rescue of cognitive impairment with a neurotrophic peptide.\" Acta Neuropathol, 2012;123(1):133-51. PMID: 22083255.", "pmid": "22083255" }, { "type": "pubmed", "citation": "Kazim SF, et al. \"Disease modifying effect of chronic oral treatment with a neurotrophic peptidergic compound in a triple transgenic mouse model of Alzheimer's disease.\" Neurobiol Dis, 2014;71:110-130. PMID: 25046994.", "pmid": "25046994" } ], "interactionCoverage": "unreviewed", "related": [ "cerebrolysin", "davunetide", "semax" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptidomimetic", "moleculeClassBasis": "peptide mimetic" }, { "id": "pal-ghk", "name": "Pal-GHK", "aliases": [ "Palmitoyl Tripeptide-1", "Palmitoyl Oligopeptide", "Pal-Gly-His-Lys" ], "tier": "stub", "category": "cosmetic", "subcategory": "topical cosmetic peptide (GHK derivative)", "class": "A lipopeptide formed by palmitoylation of the GHK tripeptide for improved skin penetration in cosmetic formulations.", "tagline": "The palmitoylated form of the GHK tripeptide (distinct from GHK-Cu) — widely used as a cosmetic ingredient in combination with Matrixyl (Matrixyl 3000 is Pal-GHK + Pal-KTTKS) for fine-line reduction.", "oneLiner": "Palmitoyl tripeptide-1, the palmitoylated form of the GHK copper-binding tripeptide, formulated as a cosmetic ingredient without the copper chelate; co-formulated with Matrixyl (Pal-KTTKS) to produce the widely used Matrixyl 3000 combination.", "sequence": "Pal-Gly-His-Lys", "molecularFormula": "C32H58N6O5", "molecularWeight": 606.84, "halfLife": { "value": null, "unit": null, "range": "topical only", "notes": "Systemic absorption from topical cosmetic formulations is minimal." }, "fdaStatus": "research-only", "approvalDetails": "Cosmetic ingredient; not a drug. Commonly co-formulated with Matrixyl.", "mechanism": "Palmitoylation of the GHK tripeptide improves skin penetration by increasing lipophilicity while retaining the signaling sequence. Proposed to stimulate fibroblast collagen synthesis and extracellular matrix remodeling similarly to GHK-Cu but without the copper-chelate component, via mechanisms that remain less well-characterized than the copper-bound form.", "primaryUses": [ "Topical cosmetic anti-aging formulations" ], "typicalDose": { "range": "3–5", "unit": "% (topical formulation)", "frequency": "twice daily", "route": "topical", "notes": "Cosmetic concentrations; often co-formulated with Pal-KTTKS (Matrixyl) as Matrixyl 3000." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "Trookman NS, et al. \"Immediate and long-term clinical benefits of a topical treatment for facial lines and wrinkles.\" J Clin Aesthet Dermatol, 2009;2:38-43. PMID: 20729942.", "pmid": "20729942" }, { "type": "manufacturer", "citation": "Sederma. \"Matrixyl 3000 technical data sheet and cosmetic ingredient profile.\"" } ], "interactionCoverage": "none-found", "related": [ "matrixyl", "ghk-cu", "argireline" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." } ], "moleculeClass": "peptide" }, { "id": "palmitoyl-hexapeptide-12", "name": "Palmitoyl Hexapeptide-12", "aliases": [ "Biopeptide EL", "Pal-VGVAPG", "Pal-Val-Gly-Val-Ala-Pro-Gly", "Elastin spring-fragment peptide" ], "tier": "stub", "category": "cosmetic", "subcategory": "topical cosmetic peptide (elastin-derived matrikine)", "class": "A palmitoylated synthetic hexapeptide (Pal-Val-Gly-Val-Ala-Pro-Gly) modeled on the \"VGVAPG\" elastin repeating motif — a recognised chemotactic and matrikine sequence — marketed by Sederma as Biopeptide EL™.", "tagline": "Biopeptide EL — a palmitoyl-VGVAPG elastin \"spring fragment\" peptide. The VGVAPG sequence is chemotactic for fibroblasts and binds the elastin receptor complex (GLB1 / cathepsin-A / NEU-1); cosmetic firmness claims rest mostly on manufacturer data.", "oneLiner": "A synthetic lipopeptide consisting of palmitic acid conjugated to Val-Gly-Val-Ala-Pro-Gly — the \"spring fragment\" of elastin, a six-residue motif repeated six times in the native human tropoelastin and released during elastin proteolytic turnover. The free VGVAPG motif is a known ligand of the elastin receptor complex (ERC: a heterotrimer of GLB1/elastin-binding-protein, cathepsin-A, and NEU-1) and is chemotactic for fibroblasts and monocytes. Sederma (Croda International) conjugated palmitic acid to the hexapeptide to create a skin-penetrating topical and marketed it as Biopeptide EL™. Manufacturer clinical data (10-volunteer open study, twice-daily 4 % application, one month) reported 33 % firmness and 20 % tone improvement; not independently replicated. Cosmetic ingredient only.", "sequence": "Pal-Val-Gly-Val-Ala-Pro-Gly", "molecularFormula": "C39H69N6O8", "molecularWeight": 750.99, "halfLife": { "value": null, "unit": null, "range": "topical only", "notes": "Systemic absorption from topical cosmetic formulations is minimal." }, "fdaStatus": "research-only", "approvalDetails": "Cosmetic ingredient; not a drug. INCI name: Palmitoyl Hexapeptide-12 (CIR-reviewed 2018). Note: two possible sequences are registered under the INCI \"Hexapeptide-12\" name; the biologically characterised one is VGVAPG.", "mechanism": "The VGVAPG motif is released from elastin by elastases and matrix metalloproteinases during aging and photoaging. Free VGVAPG binds the elastin receptor complex (ERC) — a non-integrin heterotrimer composed of the elastin-binding protein (splice variant of β-galactosidase, GLB1), cathepsin-A, and neuraminidase-1 (NEU-1) — triggering ERK1/2 MAP-kinase signalling. Downstream effects in fibroblasts include chemotaxis, upregulation of MMP-1 (elastase activity) and, per manufacturer claims, stimulation of tropoelastin and collagen synthesis. The palmitoyl tail provides the lipophilicity required for stratum corneum partitioning. Cosmetic claims for firmness and tone rest primarily on manufacturer data; the underlying ERC signalling is well-characterised in elastin biology literature.", "primaryUses": [ "Topical cosmetic anti-aging formulations (firmness / tone)" ], "typicalDose": { "range": "3–4", "unit": "% (finished formulation, as supplied solution)", "frequency": "twice daily", "route": "topical", "notes": "Cosmetic concentrations. Manufacturer in-house clinical study used 4 % twice-daily application." }, "evidenceLevel": "low", "sources": [ { "type": "manufacturer", "citation": "Sederma (Croda International). \"Biopeptide EL™ (Palmitoyl Hexapeptide-12) technical data sheet.\"" }, { "type": "review", "citation": "Johnson W Jr, Bergfeld WF, Belsito DV, et al. \"Safety Assessment of Tripeptide-1, Hexapeptide-12, their metal salts and fatty acyl derivatives, and Palmitoyl Tetrapeptide-7 as used in cosmetics.\" Int J Toxicol, 2018;37(Suppl 3):90S-102S (CIR review)." }, { "type": "pubmed", "citation": "Senior RM, Griffin GL, Mecham RP. \"Chemotactic activity of elastin-derived peptides.\" J Clin Invest, 1980;66(4):859-862 (VGVAPG chemotactic characterization). PMID: 6903189.", "pmid": "6903189" } ], "interactionCoverage": "unreviewed", "related": [ "matrixyl", "pal-ghk", "rigin" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." } ], "moleculeClass": "peptide" }, { "id": "palmitoyl-pentapeptide-4", "name": "Palmitoyl Pentapeptide-4", "aliases": [ "Matrixyl", "Pal-KTTKS" ], "tier": "mid", "category": "cosmetic", "subcategory": "topical cosmetic peptide", "class": "A lipidated pentapeptide fragment of type I procollagen C-terminal propeptide, used in topical anti-aging formulations to stimulate collagen and fibronectin synthesis.", "tagline": "The palmitoylated procollagen fragment sold as Matrixyl (pal-KTTKS): in a 12-week split-face trial in 93 women a moisturiser containing it reduced wrinkles more than the same moisturiser alone. A cosmetic ingredient, not a drug.", "oneLiner": "A palmitoyl-conjugated pentapeptide (Lys-Thr-Thr-Lys-Ser) derived from the type I procollagen C-propeptide sequence, which acts as a matrikine — a matrix fragment that signals fibroblasts to upregulate collagen I, collagen III, and fibronectin production.", "sequence": "Pal-Lys-Thr-Thr-Lys-Ser", "molecularFormula": "C39H75N7O10", "molecularWeight": 802.1, "halfLife": { "value": null, "unit": null, "range": "Topical only; not a systemic drug", "notes": "In hairless mouse skin it stayed within the skin layers and did not cross full-thickness skin (PMID 25143811).", "source": { "type": "qualitative", "note": "a description with no figure; no half-life measurement is cited for it" } }, "fdaStatus": "research-only", "approvalDetails": "Not a drug. Widely used as a cosmetic ingredient (Sederma trademark Matrixyl). Regulated as a cosmetic, not a drug. Present in hundreds of anti-aging skincare products.", "mechanism": "Acts as a matrikine (extracellular matrix fragment with signaling activity). The KTTKS sequence mimics a feedback signal from collagen degradation, binding to fibroblast surface receptors and upregulating expression of collagen I, collagen III, and fibronectin via TGF-β pathway activation. The palmitoyl group enables stratum corneum penetration.", "primaryUses": [ "Anti-aging topical skincare", "Wrinkle reduction formulations", "Post-procedure skin recovery products" ], "typicalDose": { "range": "3", "unit": "ppm (in the 2005 trial cream)", "frequency": "daily topical application", "route": "topical", "notes": "The 2005 split-face trial used a moisturiser containing 3 ppm pal-KTTKS for 12 weeks. The earlier '2-8% of Matrixyl' figure had no source." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "Robinson LR, et al. \"Topical palmitoyl pentapeptide provides improvement in photoaged human facial skin.\" Int J Cosmet Sci, 2005;27(3):155-60. PMID: 18492182.", "pmid": "18492182" }, { "type": "pubmed", "citation": "Aruan RR, et al. \"Double-blind, Randomized Trial on the Effectiveness of Acetylhexapeptide-3 Cream and Palmitoyl Pentapeptide-4 Cream for Crow's Feet.\" J Clin Aesthet Dermatol, 2023;16(2):37-43. PMID: 36909866.", "pmid": "36909866" }, { "type": "pubmed", "citation": "Choi YL, et al. \"Dermal Stability and In Vitro Skin Permeation of Collagen Pentapeptides (KTTKS and palmitoyl-KTTKS).\" Biomol Ther (Seoul), 2014;22(4):321-7. PMID: 25143811.", "pmid": "25143811" }, { "type": "pubmed", "citation": "Park H, et al. \"Effect of Palmitoyl-Pentapeptide (Pal-KTTKS) on Wound Contractile Process in Relation with Connective Tissue Growth Factor and α-Smooth Muscle Actin Expression.\" Tissue Eng Regen Med, 2017;14(1):73-80. PMID: 30603464.", "pmid": "30603464" }, { "type": "pubmed", "citation": "Kachooeian M, et al. \"Matrixyl Patch vs Matrixyl Cream: A Comparative In Vivo Investigation of Matrixyl (MTI) Effect on Wound Healing.\" ACS Omega, 2022;7(28):24695-24704. PMID: 35874243.", "pmid": "35874243" }, { "type": "fda", "citation": "U.S. Food and Drug Administration. FDA authority over cosmetics: cosmetic products and ingredients, other than color additives, do not need FDA premarket approval. Content current as of November 18, 2025; read September 30, 2026." } ], "interactionCoverage": "none-found", "related": [ "matrixyl", "argireline", "collagen-peptides", "ghk-cu" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-20", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." } ], "moleculeClass": "peptide" }, { "id": "palmitoyl-tetrapeptide-7", "name": "Palmitoyl Tetrapeptide-7", "aliases": [ "Pal-GQPR", "Palmitoyl Tetrapeptide-3", "Rigin Palmitoyl" ], "tier": "stub", "category": "cosmetic", "subcategory": "Anti-inflammatory cosmeceutical peptide", "class": "Palmitoyl Tetrapeptide-7 is the anti-inflammatory half of the popular Matrixyl 3000 complex, working synergistically with Palmitoyl Tripeptide-1 to reduce skin aging.", "tagline": "The anti-inflammatory partner in Matrixyl 3000 — a lipopeptide that reduces IL-6 and glycation damage in aging skin.", "oneLiner": "A lipopeptide (palmitoyl-GQPR) that reduces IL-6 secretion and glycation-induced inflammation in the skin, commonly paired with Palmitoyl Tripeptide-1 as the commercial complex Matrixyl 3000.", "sequence": "Pal-GQPR", "molecularFormula": "C33H57N7O9", "molecularWeight": 699.85, "halfLife": { "value": null, "unit": null, "range": "Hours (topical)", "notes": "The palmitoyl tail enhances skin penetration and dermal retention." }, "fdaStatus": "supplement", "approvalDetails": "Cosmetic ingredient, not FDA-approved as a drug. Commercially available as Matrixyl 3000 (Sederma/Croda).", "mechanism": "Reduces IL-6 secretion from keratinocytes and fibroblasts, dampening inflammaging that accelerates collagen degradation. Combined with Palmitoyl Tripeptide-1 (collagen stimulator) for dual-mechanism anti-aging.", "primaryUses": [ "Anti-aging cosmeceutical (Matrixyl 3000)", "Reducing skin inflammation", "Anti-glycation" ], "typicalDose": { "range": "2-5", "unit": "% in formulation", "frequency": "1-2 times daily", "route": "topical", "notes": "Used in serums and creams." }, "evidenceLevel": "low", "sources": [ { "type": "other", "citation": "Schagen SK. \"Topical peptide treatments with effective anti-aging results.\" Cosmetics, 2017;4(2):16. doi:10.3390/cosmetics4020016 (MDPI Cosmetics is not indexed in PubMed, so no PMID exists)." } ], "interactionCoverage": "none-found", "related": [ "palmitoyl-tripeptide-38", "palmitoyl-tripeptide-5", "palmitoyl-pentapeptide-4", "matrixyl", "rigin" ], "lastReviewed": "2026-04-21", "publishedAt": "2026-04-21", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." } ], "moleculeClass": "peptide" }, { "id": "palmitoyl-tripeptide-38", "name": "Palmitoyl Tripeptide-38", "aliases": [ "Matrixyl Synthe'6", "Matrixyl S6", "Pal-KMO2K", "Pal-Lys-Met(O2)-Lys" ], "tier": "stub", "category": "cosmetic", "subcategory": "topical cosmetic peptide (matrikine lipopeptide)", "class": "A palmitoylated synthetic tripeptide (palmitic acid conjugated to Lys-Met(O2)-Lys, where Met(O2) is methionine sulfone) marketed by Sederma as Matrixyl™ Synthe'6 — the successor matrikine ingredient to Matrixyl 3000.", "tagline": "Sederma's Matrixyl Synthe'6 — a palmitoyl tripeptide (Pal-KMO2K) claimed to stimulate six dermal-matrix components (collagens I / III / IV, fibronectin, hyaluronic acid, laminin-5). Follow-on to Matrixyl and Matrixyl 3000; almost all efficacy data is manufacturer-generated.", "oneLiner": "A synthetic lipopeptide consisting of palmitic acid conjugated to the tripeptide Lys-Met(O2)-Lys, where the central methionine is oxidised to the sulfone. Developed by Sederma (Croda International) and launched in 2011 under the trade name Matrixyl™ Synthe'6; CAS numbers 128446-35-5 and 1447824-23-8 appear in supplier literature. In-vitro manufacturer studies on contracted collagen lattices reported stimulation of six extracellular-matrix components (collagens I, III, IV; fibronectin; hyaluronic acid; laminin-5) with a claimed 31–100 % reduction in wrinkle depth after two months of 2 % topical application; independent replication is limited. Cosmetic ingredient only; no regulated clinical-drug development.", "sequence": "Pal-Lys-Met(O2)-Lys", "molecularFormula": "C34H66N4O7S", "molecularWeight": 674.98, "halfLife": { "value": null, "unit": null, "range": "topical only", "notes": "Systemic absorption from topical cosmetic formulations is minimal; lipophilic palmitoyl tail aids stratum corneum partitioning." }, "fdaStatus": "research-only", "approvalDetails": "Cosmetic ingredient; not a drug. INCI name: Palmitoyl Tripeptide-38.", "mechanism": "Classified as a matrikine-mimetic signalling peptide. The palmitoyl chain provides stratum corneum penetration and the tripeptide motif (derived from collagen-VI chain-region analysis) is proposed to bind fibroblast surface receptors and trigger transcriptional upregulation of multiple extracellular-matrix components. In-vitro collagen-lattice assays show increases in collagen I, collagen III, collagen IV, fibronectin, hyaluronic acid, and laminin-5 — the \"six\" of the Synthe'6 trade name. Methionine sulfone substitution is claimed to improve oxidative stability versus standard methionine. Independent mechanistic replication outside Sederma is limited.", "primaryUses": [ "Topical cosmetic anti-aging formulations (wrinkle filling / dermal-epidermal junction support)" ], "typicalDose": { "range": "2", "unit": "% (finished formulation, as supplied 2 % solution)", "frequency": "twice daily", "route": "topical", "notes": "Cosmetic concentrations. Supplied by the manufacturer as a pre-solubilised solution with recommended use-rate of 2 % in finished product." }, "evidenceLevel": "low", "sources": [ { "type": "manufacturer", "citation": "Sederma (Croda International). \"Matrixyl™ Synthe'6 (Palmitoyl Tripeptide-38) technical data sheet.\" Awarded the in-cosmetics 25 Years of Innovation Award, 2015." }, { "type": "review", "citation": "Errante F, Ledwoń P, Latajka R, Rovero P, Papini AM. \"Cosmeceutical peptides in the framework of sustainable wellness economy.\" Front Chem, 2020;8:572923. PMID: 33195061.", "pmid": "33195061" }, { "type": "other", "citation": "Schagen SK. \"Topical peptide treatments with effective anti-aging results.\" Cosmetics, 2017;4(2):16. doi:10.3390/cosmetics4020016 (MDPI Cosmetics is not indexed in PubMed, so no PMID exists)." } ], "interactionCoverage": "unreviewed", "related": [ "matrixyl", "pal-ghk", "rigin" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." } ], "moleculeClass": "peptide" }, { "id": "palmitoyl-tripeptide-5", "name": "Palmitoyl Tripeptide-5", "aliases": [ "Syn-Coll", "SYN-COLL", "Pal-Lys-Val-Lys", "Pal-KVK" ], "tier": "stub", "category": "cosmetic", "subcategory": "topical cosmetic peptide (thrombospondin-1 mimetic / TGF-β activator)", "class": "A palmitoylated synthetic tripeptide (Pal-Lys-Val-Lys) modeled on a fragment of the thrombospondin-1 (TSP-1) sequence that activates latent TGF-β; marketed by DSM-Firmenich (originally Pentapharm / DSM Nutritional Products) as Syn®-Coll.", "tagline": "Syn-Coll / Pal-KVK — a palmitoyl tripeptide modeled on the thrombospondin-1 motif that activates latent TGF-β. Mechanistically distinct from Matrixyl-family matrikines: activates a growth-factor signalling pathway rather than directly mimicking collagen fragments. Cosmetic ingredient only.", "oneLiner": "A synthetic lipopeptide (Palmitoyl-Lys-Val-Lys, CAS 623172-56-5) modeled on the KRFK motif of thrombospondin-1 (TSP-1) that is known to activate latent extracellular TGF-β in vivo; the simplified KVK tripeptide is claimed by the manufacturer to reproduce the TSP-1 activity in topical formulations. Originally developed by Pentapharm (subsequently DSM, now DSM-Firmenich / dsm-firmenich) and marketed as Syn®-Coll; INCI designation Palmitoyl Tripeptide-5 (formerly Palmitoyl Tripeptide-3). Primary preclinical evidence comes from manufacturer-sponsored collagen-induction and wrinkle-reduction studies; independent replication is limited. Cosmetic ingredient only; no drug-development program.", "sequence": "Pal-Lys-Val-Lys", "molecularFormula": "C33H65N5O5", "molecularWeight": 611.91, "halfLife": { "value": null, "unit": null, "range": "topical only", "notes": "Systemic absorption from topical cosmetic formulations is minimal; lipophilic palmitoyl tail aids stratum corneum partitioning." }, "fdaStatus": "research-only", "approvalDetails": "Cosmetic ingredient; not a drug. INCI name: Palmitoyl Tripeptide-5 (formerly Palmitoyl Tripeptide-3).", "mechanism": "Modeled on the Lys-Arg-Phe-Lys (KRFK) motif of thrombospondin-1 (TSP-1), a matricellular glycoprotein that activates latent TGF-β by inducing a conformational change in the LAP–LTBP–TGF-β complex. The simplified Pal-KVK structure is proposed by the manufacturer to reproduce the TSP-1 latent-TGF-β–activating activity; activated TGF-β then engages SMAD2/3-dependent fibroblast transcription, upregulating collagen I and III synthesis. In-vitro fibroblast assays from the manufacturer report a 2–3-fold increase in collagen production over baseline. This mechanism — growth-factor pathway activation rather than direct matrikine mimicry — distinguishes Syn-Coll from the Matrixyl and Rigin families. Independent mechanistic confirmation is limited.", "primaryUses": [ "Topical cosmetic anti-aging formulations (collagen stimulation / wrinkle reduction)" ], "typicalDose": { "range": "2–5", "unit": "% (finished formulation, as supplied solution)", "frequency": "twice daily", "route": "topical", "notes": "Cosmetic concentrations. Supplied as water-soluble solution; typical recommended finished-product use level 2–5 %." }, "evidenceLevel": "low", "sources": [ { "type": "manufacturer", "citation": "DSM / dsm-firmenich. \"Syn®-Coll (Palmitoyl Tripeptide-5) technical data sheet.\" CAS 623172-56-5. Formerly marketed by Pentapharm." }, { "type": "pubmed", "citation": "Murphy-Ullrich JE, Poczatek M. \"Activation of latent TGF-beta by thrombospondin-1: mechanisms and physiology.\" Cytokine Growth Factor Rev, 2000;11(1-2):59-69 (TSP-1/TGF-β mechanistic basis). PMID: 10708953.", "pmid": "10708953" }, { "type": "pubmed", "citation": "Katayama K, et al. \"A pentapeptide from type I procollagen promotes extracellular matrix production.\" J Biol Chem, 1993;268(14):9941-4. PMID: 8486721.", "pmid": "8486721" } ], "interactionCoverage": "none-found", "related": [ "matrixyl", "pal-ghk", "palmitoyl-tripeptide-38" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." } ], "moleculeClass": "peptide" }, { "id": "pasireotide", "name": "Pasireotide", "aliases": [ "Signifor", "Signifor LAR", "SOM230" ], "tier": "mid", "category": "growth-hormone", "subcategory": "somatostatin analog", "class": "A hexapeptide somatostatin analog with broad receptor binding (sst1,2,3,4,5), particularly potent at sst5, for Cushing's disease and acromegaly.", "tagline": "The somatostatin analog for Cushing's disease — the only FDA-approved medical therapy targeting pituitary ACTH secretion, with uniquely broad somatostatin receptor affinity.", "oneLiner": "A cyclohexapeptide somatostatin analog with 40-fold higher affinity for sst5 than octreotide, FDA-approved for Cushing's disease (the only approved medical therapy targeting the pituitary) and acromegaly.", "sequence": "Cyclo[4-aminoPhe(2-amino)-D-Trp-Lys-Thr(Bzl)-Phe] (cyclohexapeptide)", "molecularFormula": "C58H66N8O9", "molecularWeight": 1047.2, "halfLife": { "value": null, "unit": null, "range": "not reported in the sources read", "source": { "type": "none", "note": "searched PubMed on October 1, 2026; no human half-life figure in the sources read" } }, "fdaStatus": "approved", "approvalDetails": "Signifor, NDA 200677, approved December 14, 2012, for adults with Cushing's disease for whom pituitary surgery is not an option or has not been curative. The label requires fasting glucose testing before dosing and intensive glucose monitoring after starting (Drugs@FDA and the label, read October 1, 2026).", "mechanism": "Pan-somatostatin receptor agonist with highest affinity for sst5 (40x octreotide), and strong binding at sst1, sst2, sst3. In Cushing's disease, sst5 activation on corticotroph adenoma cells suppresses ACTH secretion. In acromegaly, sst2/sst5 co-activation suppresses GH more broadly than octreotide. Hyperglycemia is a major side effect (sst5-mediated suppression of insulin).", "primaryUses": [ "Cushing's disease (pituitary ACTH suppression)", "Acromegaly (octreotide-refractory)", "Neuroendocrine tumor research" ], "typicalDose": { "range": "0.3-0.9", "unit": "mg", "frequency": "twice daily", "route": "subcutaneous", "notes": "Signifor label: start at 0.6 mg or 0.9 mg subcutaneously twice a day, range 0.3 to 0.9 mg twice daily, titrated on 24-hour urinary free cortisol and tolerability. Test fasting plasma glucose before dosing." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Signifor (pasireotide) prescribing information, sections 1, 2, 5 and 6 (DailyMed SPL version 20, effective February 17, 2026; read October 1, 2026)." }, { "type": "pubmed", "citation": "Colao A, et al. \"A 12-month phase 3 study of pasireotide in Cushing's disease.\" N Engl J Med, 2012;366(10):914-24. PMID: 22397653.", "pmid": "22397653" }, { "type": "pubmed", "citation": "Gadelha MR, et al. \"Pasireotide versus continued treatment with octreotide or lanreotide in patients with inadequately controlled acromegaly (PAOLA): a randomised, phase 3 trial.\" Lancet Diabetes Endocrinol, 2014;2(11):875-84. PMID: 25260838.", "pmid": "25260838" }, { "type": "pubmed", "citation": "Petersenn S, et al. \"Pasireotide (SOM230) demonstrates efficacy and safety in patients with acromegaly: a randomized, multicenter, phase II trial.\" J Clin Endocrinol Metab, 2010;95(6):2781-9. PMID: 20410233.", "pmid": "20410233" }, { "type": "pubmed", "citation": "Breitschaft A, et al. \"Management of hyperglycemia associated with pasireotide (SOM230): healthy volunteer study.\" Diabetes Res Clin Pract, 2014;103(3):458-65. PMID: 24461109.", "pmid": "24461109" }, { "type": "pubmed", "citation": "Breitschaft A, et al. \"Effects of Subcutaneous Pasireotide on Cardiac Repolarization in Healthy Volunteers: a Single‐Center, Phase I, Randomized, Four‐Way Crossover Study.\" J Clin Pharmacol, 2014;54(1):75-86. PMID: 24242903.", "pmid": "24242903" } ], "interactionCoverage": "label", "related": [ "octreotide", "lanreotide", "somatropin-hgh" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-20", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "pb-718", "name": "PB-718", "aliases": [ "PB718" ], "tier": "stub", "category": "pipeline", "subcategory": "GLP-1 / GLP-2 dual agonist (Phase 2)", "class": "A dual GLP-1 / GLP-2 receptor agonist peptide developed by PegBio (China).", "tagline": "PegBio's dual GLP-1 / GLP-2 agonist — an unusual combination targeting both the incretin axis and intestinal mucosal trophic signaling; Phase 2 in T2DM and NAFLD.", "oneLiner": "A long-acting dual GLP-1 / GLP-2 receptor agonist peptide developed by PegBio (Suzhou, China), in Phase 2 for type 2 diabetes and non-alcoholic fatty liver disease; an unusual dual combination that adds GLP-2 (intestinal mucosal trophic) signaling to standard GLP-1 incretin agonism, with the pharmacological rationale of protecting the intestinal barrier against GLP-1-driven GI side effects while adding direct intestinal-growth benefit.", "sequence": null, "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": "hours", "range": "supports weekly dosing", "notes": "PEGylated long-acting peptide." }, "fdaStatus": "clinical-trials", "approvalDetails": "Not approved. Phase 2 in China for type 2 diabetes and NAFLD.", "mechanism": "Dual agonism at GLP-1 and GLP-2 receptors. GLP-1: standard incretin effects. GLP-2: intestinotrophic signaling — enterocyte proliferation, villous growth, tight-junction integrity — which in theory mitigates GLP-1-related GI inflammation and preserves intestinal barrier function.", "primaryUses": [ "Type 2 diabetes mellitus (Phase 2)", "NAFLD/MASLD (Phase 2)" ], "typicalDose": { "range": null, "unit": null, "frequency": "once weekly", "route": "subcutaneous", "notes": "Phase 2 doses not publicly finalized." }, "evidenceLevel": "low", "sources": [ { "type": "manufacturer", "citation": "PegBio Co., Ltd. Pipeline disclosures — PB-718 dual GLP-1/GLP-2 agonist." } ], "interactionCoverage": "none-found", "related": [ "semaglutide", "teduglutide", "apraglutide" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." } ], "moleculeClass": "peptide" }, { "id": "pe-22-28", "name": "PE-22-28", "aliases": [ "PE22-28", "spadin" ], "tier": "stub", "category": "cognitive", "subcategory": "antidepressant research peptide", "class": "Synthetic 7-amino-acid peptide derived from the propeptide region of sortilin; a selective blocker of the TREK-1 potassium channel.", "tagline": "A short peptide that selectively blocks the TREK-1 potassium channel — studied in animal models as a fast-acting antidepressant candidate.", "oneLiner": "A 7-amino-acid peptide derived from the propeptide of sortilin that selectively inhibits the TREK-1 two-pore potassium channel, producing antidepressant-like effects in rodent models with an onset of hours rather than weeks.", "sequence": "AVPLPAG", "molecularFormula": "C28H48N6O8", "molecularWeight": 596.7, "halfLife": { "value": null, "unit": null, "range": "undetermined in humans", "notes": "Short plasma half-life expected; rodent studies support bolus dosing." }, "fdaStatus": "research-only", "approvalDetails": "Not approved. Preclinical-stage research peptide. No completed human clinical trials identified.", "mechanism": "Selective blockade of the TREK-1 (TWIK-related potassium-1) channel, a two-pore-domain potassium channel implicated in mood regulation. TREK-1 knockout mice show a depression-resistant phenotype; pharmacological inhibition with PE-22-28 reproduces this phenotype in wild-type rodents, with antidepressant-like effects appearing within hours — substantially faster than SSRIs.", "primaryUses": [ "Rodent depression models", "TREK-1 channel pharmacology research" ], "typicalDose": { "range": "preclinical only", "unit": "", "frequency": "varies", "route": "IV, IP (preclinical)", "notes": "No human dosing established. Community use carries unknown risk; not medical guidance." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Mazella J, et al. \"Spadin, a sortilin-derived peptide, targeting rodent TREK-1 channels: a new concept in the antidepressant drug design.\" PLoS Biol, 2010;8:e1000355. PMID: 20405001.", "pmid": "20405001" }, { "type": "pubmed", "citation": "Djillani A, et al. \"Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability, and Antidepressant Activity.\" Front Pharmacol, 2017;8:643. PMID: 28955242.", "pmid": "28955242" } ], "interactionCoverage": "none-found", "related": [ "selank", "semax" ], "lastReviewed": "2026-04-18", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "peg-mgf", "name": "PEG-MGF", "aliases": [ "Pegylated MGF", "PEGylated mechano-growth factor", "PEG Mechano Growth Factor" ], "tier": "stub", "category": "research", "subcategory": "IGF-1 splice-variant analog", "class": "A pegylated synthetic E-domain peptide derived from the IGF-1Ec splice variant (\"mechano-growth factor\").", "tagline": "A pegylated fragment of a proposed muscle-specific IGF-1 splice variant — the underlying \"MGF\" biology remains scientifically contested, and PEG-MGF itself has no human clinical data.", "oneLiner": "A pegylated synthetic peptide corresponding to the 24-amino-acid E-domain of the IGF-1Ec splice variant (named \"mechano-growth factor\" by Goldspink based on its upregulation after mechanical loading of rodent muscle), with PEGylation intended to extend the very short plasma half-life of the unconjugated peptide.", "sequence": "YQPPSTNKNTKSQRRKGSTFEERK (E-domain portion, pegylated)", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": null, "range": "native MGF ~5–7 minutes; PEG-MGF claimed hours (unverified in humans)", "notes": "Native MGF E-peptide is rapidly cleared; PEG conjugation extends half-life in rodent models, but human PK data for PEG-MGF does not exist in the peer-reviewed literature." }, "fdaStatus": "research-only", "approvalDetails": "Not approved for any indication. The underlying \"mechano-growth factor\" concept, popularized by Geoffrey Goldspink's group in the 1990s–2000s, remains disputed — multiple independent labs have questioned whether IGF-1Ec produces a biologically active standalone E-peptide in humans at all.", "mechanism": "Proposed mechanism: the MGF E-peptide acts on a receptor distinct from IGF-1R (unidentified) to drive satellite cell activation, myoblast proliferation, and local muscle hypertrophy after mechanical loading. Rodent overexpression and injection studies have shown effects on muscle fiber regeneration. Human validation of a distinct MGF receptor is lacking, and some groups argue the observed effects are artifacts of the IGF-1 mature domain rather than a genuine E-peptide activity.", "primaryUses": [ "Muscle biology research (contested)", "Community bodybuilding use (unapproved, mechanism disputed)" ], "typicalDose": { "range": "research-only", "unit": "", "frequency": "varies", "route": "subcutaneous or intramuscular (community)", "notes": "No human clinical dosing. Community protocols range widely and have no evidence base." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Goldspink G. \"Mechanical signals, IGF-I gene splicing, and muscle adaptation.\" Physiology (Bethesda), 2005;20:232-238. PMID: 16024511.", "pmid": "16024511" }, { "type": "pubmed", "citation": "Matheny RW Jr, Nindl BC, Adamo ML. \"Minireview: Mechano-growth factor: a putative product of IGF-I gene expression involved in tissue repair and regeneration.\" Endocrinology, 2010;151:865-875. PMID: 20130113.", "pmid": "20130113" } ], "interactionCoverage": "unreviewed", "related": [ "mgf", "igf-1-lr3", "igf-1-des", "follistatin-344" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.3", "named": false, "wording": "Mechano growth factors (MGFs)", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "PEG-MGF itself is not named: it is a pegylated mechano growth factor, caught by S2's rule covering substances of similar chemical structure or biological effect." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.3", "named": false, "wording": "Mechano growth factors (MGFs)", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "PEG-MGF itself is not named: it is a pegylated mechano growth factor, caught by S2's rule covering substances of similar chemical structure or biological effect." } ], "moleculeClass": "peptide" }, { "id": "pegvisomant", "name": "Pegvisomant", "aliases": [ "Somavert", "B2036-PEG" ], "tier": "mid", "category": "growth-hormone", "subcategory": "growth hormone receptor antagonist", "class": "A PEGylated recombinant analog of human growth hormone engineered to bind the GH receptor without triggering productive signaling — functioning as a competitive receptor antagonist rather than an agonist.", "tagline": "Pfizer's GH receptor antagonist (Somavert) — FDA-approved in 2003 for acromegaly; important to distinguish from GH agonists because it does the opposite (blocks GH action rather than supplementing it).", "oneLiner": "A PEGylated recombinant growth hormone analog engineered to bind the GH receptor's primary binding site with higher affinity than native GH while carrying amino acid substitutions at the secondary binding site that prevent functional receptor dimerization — making it a competitive GH receptor antagonist. FDA-approved as Somavert in 2003 for acromegaly in patients who have had inadequate response to surgery, radiation, or somatostatin analogs. Important to distinguish from GH agonists because it *suppresses* GH action and lowers IGF-1; confusing it with a GH-enhancing product is a common internet search error.", "sequence": "Modified recombinant hGH with 9 amino acid substitutions (including G120K at binding site 2) conjugated to 4–6 PEG moieties", "molecularFormula": null, "molecularWeight": 47000, "halfLife": { "value": null, "unit": "hours", "range": "60 to 138 hours (mean estimates after single or multiple doses)", "source": { "type": "label", "ref": "Somavert (pegvisomant) prescribing information, sections 1, 2, 5, 7 and 12.3 (DailyMed SPL version 13, effective December 18, 2025; read October 1, 2026)" } }, "fdaStatus": "approved", "approvalDetails": "Somavert, application 021106, approved March 25, 2003, for acromegaly in patients with an inadequate response to surgery or radiation therapy, or for whom these are not appropriate; the goal of treatment is to normalise IGF-1. Drugs@FDA now lists it as BLA 021106 (Drugs@FDA and the label, read October 1, 2026).", "mechanism": "Competitive antagonism at the GH receptor. Native GH binds its receptor at two sites (binding site 1 with high affinity, binding site 2 with lower affinity) and the second interaction drives receptor dimerization and JAK2/STAT5 signaling. Pegvisomant carries a G120K substitution (and several other changes) that abolish binding site 2 while leaving binding site 1 intact — the drug therefore occupies the receptor and prevents productive dimerization by native GH, lowering IGF-1 generation. PEGylation extends half-life and reduces immunogenicity. Serum IGF-1 is the primary pharmacodynamic marker for titration.", "primaryUses": [ "Acromegaly (second- or third-line after surgery, radiation, or somatostatin analogs)" ], "typicalDose": { "range": "10-30", "unit": "mg", "frequency": "once daily, after a 40 mg loading dose", "route": "subcutaneous", "notes": "Somavert label: a 40 mg loading dose under supervision, then 10 mg daily from the next day, adjusted in 5 mg increments or decrements until IGF-1 is in the age-adjusted normal range, within 10 to 30 mg once daily. Do not adjust by growth hormone levels or symptoms; check liver tests before the first dose." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Somavert (pegvisomant) prescribing information, sections 1, 2, 5, 7 and 12.3 (DailyMed SPL version 13, effective December 18, 2025; read October 1, 2026)." }, { "type": "pubmed", "citation": "Trainer PJ, et al. \"Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant.\" N Engl J Med, 2000;342(16):1171-7. PMID: 10770982.", "pmid": "10770982" }, { "type": "pubmed", "citation": "Buchfelder M, et al. \"Long-term treatment with pegvisomant: observations from 2090 acromegaly patients in ACROSTUDY.\" Eur J Endocrinol, 2018;179(6):419-427. PMID: 30325178.", "pmid": "30325178" }, { "type": "pubmed", "citation": "Feola T, et al. \"Pegvisomant Improves Glucose Metabolism in Acromegaly: A Meta-Analysis of Prospective Interventional Studies.\" J Clin Endocrinol Metab, 2019;104(7):2892-2902. PMID: 30869797.", "pmid": "30869797" }, { "type": "pubmed", "citation": "Higham CE, et al. \"Pegvisomant improves insulin sensitivity and reduces overnight free fatty acid concentrations in patients with acromegaly.\" J Clin Endocrinol Metab, 2009;94(7):2459-63. PMID: 19366854.", "pmid": "19366854" }, { "type": "pubmed", "citation": "van der Lely AJ, et al. \"Long-term safety of pegvisomant in patients with acromegaly: comprehensive review of 1288 subjects in ACROSTUDY.\" J Clin Endocrinol Metab, 2012;97(5):1589-97. PMID: 22362824.", "pmid": "22362824" } ], "interactionCoverage": "partial", "related": [ "somatropin", "lanreotide", "octreotide" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S2.2.3", "named": false, "wording": "", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "A modified growth hormone that blocks the GH receptor. S2.2.3 covers growth hormone analogues and S2 covers substances of similar chemical structure; the List does not say whether that reaches an antagonist." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S2.2.3", "named": false, "wording": "", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "A modified growth hormone that blocks the GH receptor. S2.2.3 covers growth hormone analogues and S2 covers substances of similar chemical structure; the List does not say whether that reaches an antagonist." } ], "moleculeClass": "protein", "moleculeClassBasis": "growth hormone" }, { "id": "pemvidutide", "name": "Pemvidutide", "aliases": [ "ALT-801" ], "tier": "stub", "category": "pipeline", "subcategory": "GLP-1 / glucagon dual receptor agonist", "class": "A once-weekly balanced 1:1 glucagon / GLP-1 dual receptor agonist peptide.", "tagline": "Altimmune's GLP-1 / glucagon co-agonist — received FDA Breakthrough Therapy Designation for MASH in January 2026 after positive IMPACT Phase 2b antifibrotic data, with Phase 3 initiation planned for 2026.", "oneLiner": "A balanced (1:1) dual glucagon and GLP-1 receptor agonist developed by Altimmune for once-weekly subcutaneous administration, being investigated for both chronic weight management and metabolic dysfunction-associated steatohepatitis (MASH), and granted FDA Breakthrough Therapy Designation for MASH on January 5, 2026.", "sequence": null, "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": "days", "range": "supports once-weekly dosing", "notes": "Specific figures not publicly disclosed." }, "fdaStatus": "clinical-trials", "approvalDetails": "Not approved. Altimmune developer. FDA Breakthrough Therapy Designation for MASH granted January 5, 2026. IMPACT Phase 2b MASH trial (48-week data released December 19, 2025) showed statistically significant improvements in non-invasive fibrosis markers (ELF, LSM) versus placebo across multiple doses. A registrational Phase 3 MASH trial is planned for initiation in 2026 using AIM-MASH AI Assist pathology scoring. Earlier MOMENTUM Phase 2 obesity trial showed ~15% weight loss at 48 weeks.", "mechanism": "Simultaneously activates the GLP-1 receptor (driving appetite suppression, delayed gastric emptying, and insulin-related metabolic effects) and the glucagon receptor (driving hepatic fat oxidation, increased energy expenditure, and direct effects on hepatocyte lipid metabolism). The 1:1 balanced dual agonism is designed to capture the weight loss of GLP-1 while adding glucagon-driven hepatic benefits — particularly relevant for MASH where liver-specific fat reduction is central to the therapeutic target.", "primaryUses": [ "MASH with moderate-to-advanced fibrosis (Phase 3 planned 2026, Breakthrough Therapy Designation)", "Chronic weight management (Phase 2 completed)" ], "typicalDose": { "range": "1.2–2.4", "unit": "mg", "frequency": "once weekly", "route": "subcutaneous", "notes": "IMPACT Phase 2b tested 1.2 mg and 1.8 mg doses in MASH; Phase 3 doses TBD." }, "evidenceLevel": "medium", "sources": [ { "type": "news-release", "citation": "Altimmune, Inc. \"Altimmune Receives FDA Breakthrough Therapy Designation for Pemvidutide in MASH.\" January 5, 2026." }, { "type": "news-release", "citation": "Altimmune, Inc. \"Altimmune Announces that Pemvidutide Achieved Key Measures of Success at 48 Weeks in IMPACT Phase 2b MASH Trial.\" December 19, 2025." } ], "interactionCoverage": "partial", "related": [ "semaglutide", "retatrutide", "survodutide", "tirzepatide" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." } ], "moleculeClass": "peptide" }, { "id": "pentapeptide-3", "name": "Pentapeptide-3", "aliases": [ "Vialox", "Pentapeptide-3V", "Gly-Pro-Arg-Pro-Ala-NH2", "GPRPA" ], "tier": "stub", "category": "cosmetic", "subcategory": "topical cosmetic peptide (nicotinic acetylcholine receptor antagonist)", "class": "A synthetic pentapeptide (Gly-Pro-Arg-Pro-Ala-NH2) developed as a topical cosmetic ingredient with a curare-mimetic mechanism — a competitive antagonist of peripheral nicotinic acetylcholine receptors at the neuromuscular junction.", "tagline": "Vialox — the \"curare-mimetic\" cosmetic peptide (GPRPA). Acts post-synaptically on peripheral nicotinic ACh receptors, unlike the pre-synaptic SNAP-25-mimetic Argireline class. Sometimes marketed as a snake-venom-inspired Botox alternative; efficacy data are primarily from the manufacturer.", "oneLiner": "A synthetic pentapeptide with the sequence Gly-Pro-Arg-Pro-Ala-NH2 (C21H37N9O5, MW 495.58), originally developed by Pentapharm as Vialox® (later designated Pentapeptide-3V). The sequence is derived from curaremimetic venom peptides and functions as a competitive antagonist at peripheral nicotinic acetylcholine receptors (nAChR) of the neuromuscular junction, producing partial muscle relaxation with no reported action on central neuronal receptors. Manufacturer animal-model data describe an 11 % reduction in skin roughness and 8 % reduction in wrinkle relief after 28 days of twice-daily topical application. Cosmetic ingredient only; no regulated clinical development.", "sequence": "Gly-Pro-Arg-Pro-Ala-NH2", "molecularFormula": "C21H37N9O5", "molecularWeight": 495.58, "halfLife": { "value": null, "unit": null, "range": "topical only", "notes": "Systemic absorption from topical cosmetic formulations is minimal; peptide is charged and not lipophilic." }, "fdaStatus": "research-only", "approvalDetails": "Cosmetic ingredient; not a drug. INCI name: Pentapeptide-3 (also marketed as Pentapeptide-3V diacetate).", "mechanism": "Competitive antagonist at peripheral nicotinic acetylcholine receptors (nAChR) on the post-synaptic membrane of skeletal-muscle motor end-plates. By occupying the ACh binding site without triggering ion-channel opening, it blocks depolarisation and reduces the frequency and intensity of muscular contractions. Reported selectivity for peripheral over central (neuronal) nAChRs means central nervous system effects are minimal at topical doses. This post-synaptic mechanism is mechanistically distinct from (and potentially complementary to) the pre-synaptic SNAP-25 competitive-inhibition mechanism of Acetyl Hexapeptide-8 (Argireline) and the enkephalin-receptor mechanism of Leuphasyl. Vialox is classified alongside tubocurarine in the competitive non-depolarising neuromuscular-blocker pharmacologic class, though with vastly lower potency.", "primaryUses": [ "Topical cosmetic anti-aging formulations (expression-line reduction; \"topical Botox alternative\")" ], "typicalDose": { "range": "2–5", "unit": "% (finished formulation)", "frequency": "twice daily", "route": "topical", "notes": "Cosmetic concentrations. Often combined with Argireline / SNAP-8 / Leuphasyl on the theory that multi-mechanism neuromuscular blockade produces additive muscle relaxation." }, "evidenceLevel": "low", "sources": [ { "type": "manufacturer", "citation": "Pentapharm / DSM / dsm-firmenich. \"Vialox® (Pentapeptide-3) technical data sheet.\"" }, { "type": "pubmed", "citation": "Servent D, Winckler-Dietrich V, Hu HY, et al. \"Only snake curaremimetic toxins with a fifth disulfide bond have high affinity for the neuronal α7 nicotinic receptor.\" J Biol Chem, 1997;272(39):24279-24286 (curaremimetic selectivity reference). PMID: 9305882.", "pmid": "9305882" }, { "type": "review", "citation": "Errante F, Ledwoń P, Latajka R, Rovero P, Papini AM. \"Cosmeceutical peptides in the framework of sustainable wellness economy.\" Front Chem, 2020;8:572923. PMID: 33195061.", "pmid": "33195061" } ], "interactionCoverage": "unreviewed", "related": [ "argireline", "snap-8", "syn-ake", "leuphasyl" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." } ], "moleculeClass": "peptide" }, { "id": "petrelintide", "name": "Petrelintide", "aliases": [ "ZP8396", "Zealand amylin analog" ], "tier": "mid", "category": "pipeline", "subcategory": "long-acting amylin analog", "class": "A long-acting amylin receptor agonist engineered for once-weekly subcutaneous dosing.", "tagline": "Zealand's weekly amylin analogue, built to mix with other drugs and tested alone in a 42-week phase 2 obesity trial.", "oneLiner": "A long-acting human amylin analogue formulated at about neutral pH, in phase 2 for weight management.", "sequence": null, "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": "days", "range": "engineered for once-weekly dosing", "notes": "Specific half-life figures not publicly disclosed; dosing regimen implies a half-life in the several-day range.", "source": { "type": "qualitative", "note": "a description with no figure; no half-life measurement is cited for it" } }, "fdaStatus": "clinical-trials", "approvalDetails": "Not approved anywhere. Developed by Zealand Pharma with Roche; phase 1 trials and the 42-week ZUPREME 1 phase 2 are published, and no application appears in Drugs@FDA.", "mechanism": "Mimics endogenous amylin — a peptide co-secreted with insulin from pancreatic beta cells in response to nutrient intake. Activates amylin receptors (calcitonin receptor + RAMP complexes) in the area postrema and related hindbrain circuits, reducing food intake by increasing satiety and, importantly, appearing to restore leptin sensitivity. The non-GLP-1 mechanism is the source of the markedly better GI tolerability profile observed in trials.", "primaryUses": [ "Weight management in obesity (phase 2)" ], "typicalDose": { "range": "up to 9", "unit": "mg", "frequency": "once weekly", "route": "subcutaneous", "notes": "ZUPREME-1 tested five target doses up to 9 mg with dose escalation every four weeks." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "Garvey WT, et al. \"Petrelintide, a human amylin analogue for the treatment of obesity (ZUPREME 1): a randomised, double-blind, placebo-controlled, phase 2 trial.\" Lancet Diabetes Endocrinol, 2026. PMID: 42810355.", "pmid": "42810355" }, { "type": "pubmed", "citation": "Brændholt Olsen M, et al. \"Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Petrelintide for Weight Management: Two Randomized, Controlled Phase 1 Trials.\" Diabetes Obes Metab, 2026;28(7):5915-5925. PMID: 42017294.", "pmid": "42017294" }, { "type": "pubmed", "citation": "Fischer Munch H, et al. \"Development of Petrelintide: a Potent, Stable, Long-Acting Human Amylin Analogue.\" J Med Chem, 2025;68(22):23925-23940. PMID: 41217931.", "pmid": "41217931" }, { "type": "other", "citation": "US FDA, Drugs@FDA (openFDA): no application for petrelintide. Read September 30, 2026." }, { "type": "other", "citation": "Roche, press release, March 5, 2026: positive topline results from the phase II ZUPREME-1 trial (NCT06662539) in 493 people with overweight or obesity, up to 10.7% mean weight loss at week 42 (efficacy estimand) against 1.7% on placebo; the release also notes the 2025 Roche-Zealand collaboration. Read September 30, 2026." }, { "type": "other", "citation": "Zealand Pharma, press release, March 5, 2026: positive phase 2 results for petrelintide in ZUPREME-1; ZUPREME-2 in people with type 2 diabetes reporting in the second half of 2026. Read September 30, 2026." } ], "interactionCoverage": "partial", "related": [ "cagrilintide", "cagrisema", "semaglutide", "tirzepatide" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." } ], "moleculeClass": "peptide" }, { "id": "pexiganan", "name": "Pexiganan", "aliases": [ "Locilex", "MSI-78", "Pexiganan acetate" ], "tier": "mid", "category": "healing", "subcategory": "Magainin-2-derived antimicrobial peptide", "class": "A 22-amino-acid synthetic analog of magainin-2 (originally isolated from African clawed frog Xenopus laevis skin) developed as a topical antimicrobial peptide for diabetic foot ulcer infection; twice rejected by the FDA despite two rounds of Phase 3 trials spanning nearly two decades.", "tagline": "A synthetic 22-amino-acid analogue of the frog-skin peptide magainin 2, tested as a 1% cream against oral ofloxacin in two phase 3 trials in 835 people with mildly infected diabetic foot ulcers; about 85-90% improved on either. Never approved.", "oneLiner": "A 22-residue synthetic cationic antimicrobial peptide analog of magainin-2, originally isolated from the skin of the African clawed frog Xenopus laevis in 1987 by Michael Zasloff. Developed by Magainin Pharmaceuticals as a 1% cream (Locilex) for topical treatment of mildly infected diabetic foot ulcers. The FDA's Anti-Infective Drugs Advisory Committee voted against approval in March 1999 despite the drug meeting non-inferiority endpoints versus oral ofloxacin, on grounds that non-inferiority to an oral antibiotic did not constitute evidence of clinical effectiveness. Dipexium Pharmaceuticals acquired the asset, conducted two additional placebo-controlled Phase 3 trials (OneStep-1 and OneStep-2) in 2016, both of which failed to show superiority of pexiganan cream over placebo cream. The company terminated development in October 2016 after the second Phase 3 failure. Stands as one of the most thoroughly tested antimicrobial peptides in human trials and an instructive case study for AMP drug development — particularly for the challenge of demonstrating clinical efficacy in mildly infected wounds where the placebo-response rate (driven by standard wound care) is high.", "sequence": "Gly-Ile-Gly-Lys-Phe-Leu-Lys-Lys-Ala-Lys-Lys-Phe-Gly-Lys-Ala-Phe-Val-Lys-Ile-Leu-Lys-Lys (amidated C-terminus)", "molecularFormula": "C122H210N32O22", "molecularWeight": 2477.2, "halfLife": { "value": null, "unit": null, "range": "Topical; minimal systemic absorption", "notes": "Used as a 1% topical cream; systemic absorption is negligible, consistent with other topical cationic peptides.", "source": { "type": "qualitative", "note": "a description with no figure; no half-life measurement is cited for it" } }, "fdaStatus": "discontinued", "approvalDetails": "Not approved: Drugs@FDA holds no application and EMA's register has no entry (both read September 30, 2026). Two phase 3 trials (studies 303 and 304) compared 1% cream with oral ofloxacin in mildly infected diabetic foot ulcers; study 303 failed to show equivalence (PMID 18990064).", "mechanism": "Forms amphipathic α-helix on contact with bacterial membranes. Cationic charge (seven lysines, zero aspartates or glutamates) drives electrostatic attraction to negatively charged bacterial outer-membrane lipopolysaccharide and inner-membrane phosphatidylglycerol / cardiolipin. Membrane permeabilization occurs via a toroidal-pore mechanism at threshold concentrations, causing rapid bactericidal activity against both Gram-positive and Gram-negative bacteria, including many antibiotic-resistant strains. Selectivity for bacterial over mammalian membranes is moderate — sufficient for topical use but not for systemic administration.", "primaryUses": [ "Mildly infected diabetic foot ulcer — proposed topical treatment (not FDA-approved; Phase 3 failure)", "Antimicrobial peptide drug-development case study" ], "typicalDose": { "range": "1% cream, applied twice daily", "unit": null, "frequency": "twice daily", "route": "topical", "notes": "Dose regimen used in OneStep Phase 3 trials. Not an approved product; the dosing information is for research reference only." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Lipsky BA, et al. \"Topical versus systemic antimicrobial therapy for treating mildly infected diabetic foot ulcers: a randomized, controlled, double-blinded, multicenter trial of pexiganan cream.\" Clin Infect Dis, 2008;47(12):1537-45. PMID: 18990064.", "pmid": "18990064" }, { "type": "pubmed", "citation": "Lamb HM, et al. \"Pexiganan acetate.\" Drugs, 1998;56(6):1047-52; discussion 1053-4. PMID: 9878992.", "pmid": "9878992" }, { "type": "pubmed", "citation": "Ge Y, et al. \"In vitro susceptibility to pexiganan of bacteria isolated from infected diabetic foot ulcers.\" Diagn Microbiol Infect Dis, 1999;35(1):45-53. PMID: 10529881.", "pmid": "10529881" }, { "type": "pubmed", "citation": "Flamm RK, et al. \"In vitro spectrum of pexiganan activity when tested against pathogens from diabetic foot infections and with selected resistance mechanisms.\" Antimicrob Agents Chemother, 2015;59(3):1751-4. PMID: 25583717.", "pmid": "25583717" }, { "type": "pubmed", "citation": "Gopinath D, et al. \"Pexiganan-incorporated collagen matrices for infected wound-healing processes in rat.\" J Biomed Mater Res A, 2005;73(3):320-31. PMID: 15800884.", "pmid": "15800884" }, { "type": "fda", "citation": "FDA. Drugs@FDA (openFDA): no application for pexiganan. Read September 30, 2026." }, { "type": "other", "citation": "European Medicines Agency. Medicines register: no entry for pexiganan. Read September 30, 2026." } ], "interactionCoverage": "none-found", "related": [ "ll-37", "omiganan" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "A discontinued drug: S0's own examples include discontinued drugs." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "A discontinued drug: S0's own examples include discontinued drugs." } ], "moleculeClass": "peptide" }, { "id": "pinealon", "name": "Pinealon", "aliases": [ "Glu-Asp-Arg", "EDR tripeptide" ], "tier": "stub", "category": "longevity", "subcategory": "Khavinson short-chain bioregulator (neuronal)", "class": "A synthetic short tripeptide proposed as a neuroprotective bioregulator, from the Khavinson peptide series.", "tagline": "A Khavinson tripeptide proposed to cross the blood–brain barrier and support neuronal gene expression in aging brain tissue — animal data in hypoxia and oxidative stress models; no Western clinical trials.", "oneLiner": "A Khavinson-group short tripeptide (Glu-Asp-Arg) proposed to cross the blood–brain barrier and act on neuronal DNA promoter regions to support survival under oxidative stress, with published animal data in cerebral hypoxia and oxidative-damage models but no controlled Western clinical evidence.", "sequence": "Glu-Asp-Arg", "molecularFormula": "C15H26N6O8", "molecularWeight": 418.4, "halfLife": { "value": null, "unit": null, "range": "undetermined", "notes": "Pharmacokinetics not characterized in Western-standard studies." }, "fdaStatus": "research-only", "approvalDetails": "Not FDA-approved. Marketed in Russia as a bioregulator supplement.", "mechanism": "Proposed to enter neurons and bind promoter regions supporting expression of antioxidant and anti-apoptotic gene programs. Animal studies from the Khavinson group report reduced neuronal damage after induced hypoxia and hydrogen-peroxide oxidative stress.", "primaryUses": [ "Investigational neuroprotection (Russian literature)", "Research into cognitive aging" ], "typicalDose": { "range": "not established", "unit": null, "frequency": "not established", "route": "oral (capsule)", "notes": "Typical supplement protocols use 10–20 mg daily for 10–20 days." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Khavinson V, et al. \"Peptide EDR prevents hypoxia-induced neuronal death in rat cortical cells.\" Bull Exp Biol Med, 2012;153:115-117." }, { "type": "pubmed", "citation": "Kolchina N, et al. \"Short peptides prevent hypoxia-induced death of cortical neurons.\" Exp Gerontol, 2016;83:131-134." } ], "interactionCoverage": "unreviewed", "related": [ "epithalon", "cortagen", "cerebrolysin" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "plecanatide", "name": "Plecanatide", "aliases": [ "Trulance", "SP-304" ], "tier": "mid", "category": "healing", "subcategory": "Guanylate cyclase-C agonist (uroguanylin analog)", "class": "A 16-amino-acid synthetic peptide guanylate cyclase-C (GC-C) agonist approved in the United States for chronic idiopathic constipation and irritable bowel syndrome with constipation; structurally modeled more closely on the endogenous GC-C ligand uroguanylin than on guanylin.", "tagline": "A uroguanylin copy that draws water into the gut: approved as Trulance for chronic constipation and IBS-C, boxed warning under age 6.", "oneLiner": "A 16-amino-acid guanylate cyclase-C agonist modelled on uroguanylin, taken as a 3 mg tablet once daily and barely absorbed.", "sequence": "Asn-Asp-Asp-Cys-Glu-Leu-Cys-Val-Asn-Val-Ala-Cys-Thr-Gly-Cys-Leu (two disulfide bonds: Cys4-Cys12, Cys7-Cys15)", "molecularFormula": "C65H104N18O26S4", "molecularWeight": 1681.9, "halfLife": { "value": null, "unit": null, "range": "Not systemically absorbed; acts luminally", "notes": "Essentially no systemic absorption at therapeutic doses; degraded by intestinal proteases with negligible plasma concentrations.", "source": { "type": "qualitative", "note": "a description with no figure; no half-life measurement is cited for it" } }, "fdaStatus": "approved", "approvalDetails": "FDA-approved as Trulance for adults with chronic idiopathic constipation and IBS with constipation; 3 mg once daily. Boxed warning: contraindicated under 6 years old after juvenile mouse deaths from dehydration. The label has no drug interactions section.", "mechanism": "Binds GC-C on the luminal surface of intestinal epithelial cells. Mechanism is otherwise identical to linaclotide: GC-C activation → intracellular cGMP rise → PKG II activation → CFTR phosphorylation → luminal chloride and bicarbonate secretion → osmotic water movement into lumen. Proposed pharmacodynamic distinction from linaclotide is pH-sensitive activity favoring the proximal small intestine (where luminal pH is slightly acidic) over the more distal gut — a feature derived from plecanatide's closer structural relationship to uroguanylin. Clinical translation of this proposed region-selective pharmacology has not been convincingly demonstrated in head-to-head trials.", "primaryUses": [ "Chronic idiopathic constipation in adults", "Irritable bowel syndrome with constipation in adults" ], "typicalDose": { "range": "3", "unit": "mg", "frequency": "once daily", "route": "oral", "notes": "Adults: 3 mg orally once daily with or without food. Can be administered whole or as a sprinkle on applesauce or in water. Contraindicated in patients <6 years. Most common adverse event is diarrhea (leading to discontinuation in ~4% of patients). Approved dose (3 mg) is higher than linaclotide (145–290 mcg) because of plecanatide's different binding affinity and pH-dependent activity profile." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Trulance (plecanatide) tablets Prescribing Information, sections 1, 2 and boxed warning (DailyMed version 15, effective April 4, 2024; read September 30, 2026)." }, { "type": "pubmed", "citation": "Miner PB Jr, et al. \"A Randomized Phase III Clinical Trial of Plecanatide, a Uroguanylin Analog, in Patients With Chronic Idiopathic Constipation.\" Am J Gastroenterol, 2017;112(4):613-621. PMID: 28169285.", "pmid": "28169285" }, { "type": "pubmed", "citation": "Brenner DM, et al. \"Efficacy, safety, and tolerability of plecanatide in patients with irritable bowel syndrome with constipation: results of two phase 3 randomized clinical trials.\" Am J Gastroenterol, 2018;113(5):735-745. PMID: 29545635.", "pmid": "29545635" }, { "type": "pubmed", "citation": "Barish CF, et al. \"Safety and tolerability of plecanatide in patients with chronic idiopathic constipation: long-term evidence from an open-label study.\" Curr Med Res Opin, 2018;34(4):751-755. PMID: 29343131.", "pmid": "29343131" }, { "type": "pubmed", "citation": "Bai T, et al. \"Efficacy and Safety of Plecanatide in Chinese Patients with Functional Constipation: A Phase III Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.\" Drugs, 2025;85(8):1033-1048. PMID: 40571893.", "pmid": "40571893" } ], "interactionCoverage": "partial", "related": [ "linaclotide" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "pnc-27", "name": "PNC-27", "aliases": [ "PNC27" ], "tier": "stub", "category": "research", "subcategory": "anticancer research peptide", "class": "Synthetic peptide consisting of an HDM-2 binding domain from the p53 protein fused to a transmembrane penetrating sequence.", "tagline": "An experimental anticancer peptide engineered to selectively disrupt cancer cell membranes that overexpress HDM-2 — preclinical research only.", "oneLiner": "A chimeric peptide combining a p53-derived HDM-2-binding sequence with a membrane-penetrating domain that induces necrotic cell death in cancer cells overexpressing HDM-2 at the plasma membrane, while sparing normal cells.", "sequence": "PPLSQETFSDLWKLLKKWKMRRNQFWVKVQRG", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": null, "range": "undetermined", "notes": "Preclinical; human pharmacokinetics not established." }, "fdaStatus": "preclinical", "approvalDetails": "Not approved. Preclinical-stage investigational anticancer peptide. No completed clinical trials identified.", "mechanism": "Selectively binds HDM-2 (the human MDM-2 homolog) expressed on the outer plasma membrane of cancer cells but not normal cells. Binding induces transmembrane pore formation and rapid necrotic cell death. The selectivity derives from the cancer-specific surface expression of HDM-2 — in normal cells, HDM-2 is intracellular and PNC-27 has minimal effect.", "primaryUses": [ "Preclinical oncology research", "Solid tumor cell-line models", "Leukemia cell-line models" ], "typicalDose": { "range": "varies", "unit": "", "frequency": "preclinical", "route": "preclinical (IV, IP)", "notes": "No human dosing established. Community use carries unknown risk; not medical guidance." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Michl J, et al. \"PNC-27, a Peptide that Binds HDM-2 on the Cancer Cell Membrane, Induces Necrosis in Human Pancreatic and Colorectal Cancer Stem Cells.\" J Cell Biochem, 2021." }, { "type": "pubmed", "citation": "Sarafraz-Yazdi E, et al. \"Anticancer peptide PNC-27 adopts an HDM-2-binding conformation and kills cancer cells by binding to HDM-2 in their membranes.\" Proc Natl Acad Sci USA, 2010;107:1918-1923. PMID: 20080680.", "pmid": "20080680" } ], "interactionCoverage": "unreviewed", "related": [], "lastReviewed": "2026-04-18", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "polymyxin-b", "name": "Polymyxin B", "aliases": [ "Poly-RX" ], "tier": "mid", "category": "immune", "subcategory": "lipopeptide antibiotic", "class": "A cyclic cationic lipopeptide antibiotic derived from Paenibacillus polymyxa, used as a last-resort treatment for multidrug-resistant gram-negative infections.", "tagline": "The gram-negative last resort — a cyclic lipopeptide antibiotic revived from the 1950s as a critical weapon against carbapenem-resistant Acinetobacter, Pseudomonas, and Klebsiella.", "oneLiner": "A cyclic decapeptide with a fatty acid tail that disrupts gram-negative bacterial outer membranes by displacing divalent cations from lipopolysaccharide (LPS), and additionally neutralizes circulating endotoxin.", "sequence": "Cyclic heptapeptide core + tripeptide side chain + 6-methyloctanoyl tail", "molecularFormula": "C55H96N16O13", "molecularWeight": 1203.5, "halfLife": { "value": 4.1, "unit": "hours", "range": "about 4.1 hours, measured in nine hospitalised adults; the label states no half-life", "source": { "type": "pmid", "pmid": "34252297", "cite": "Nichols, K. R. et al. (2021). Pharmacokinetics of Polymyxin B in Hospitalized Adults with Cystic Fibrosis. Antimicrob Agents Chemother. PMID: 34252297." } }, "fdaStatus": "approved", "approvalDetails": "Polymyxin B sulfate for injection; the earliest record in Drugs@FDA is ANDA 060716, June 29, 1964 (read October 1, 2026). Indicated for infections caused by susceptible Pseudomonas aeruginosa and certain other gram-negative bacteria when less toxic drugs are ineffective.", "mechanism": "The cationic peptide ring displaces Ca²⁺ and Mg²⁺ from the anionic phosphate groups of lipid A in gram-negative LPS, destabilizing the outer membrane. Subsequent insertion of the fatty acid tail into the inner membrane causes permeabilization and cell death. Also binds and neutralizes free LPS (endotoxin), potentially reducing sepsis-associated inflammation.", "primaryUses": [ "Carbapenem-resistant gram-negative infections", "Multidrug-resistant Pseudomonas aeruginosa", "MDR Acinetobacter baumannii", "Endotoxin neutralization (hemoperfusion)" ], "typicalDose": { "range": "15,000-25,000", "unit": "units/kg/day", "frequency": "in divided doses every 12 hours", "route": "intravenous", "notes": "Polymyxin B sulfate label: 15,000 to 25,000 units/kg/day for adults and children with normal kidney function, never above 25,000 units/kg/day, reduced for kidney impairment. Infants with normal kidneys may receive up to 40,000 units/kg/day." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Polymyxin B sulfate for injection prescribing information, boxed warning, Indications, Dosage and Administration and Precautions (DailyMed SPL version 13, effective June 22, 2026; read October 1, 2026)." }, { "type": "pubmed", "citation": "Dellinger RP, et al. \"Effect of Targeted Polymyxin B Hemoperfusion on 28-Day Mortality in Patients With Septic Shock and Elevated Endotoxin Level: The EUPHRATES Randomized Clinical Trial.\" JAMA, 2018;320(14):1455-1463. PMID: 30304428.", "pmid": "30304428" }, { "type": "pubmed", "citation": "Neyra JA, et al. \"Polymyxin B haemoadsorption in endotoxic septic shock (Tigris): a multicentre, open-label, Bayesian, randomised, controlled, phase 3 trial.\" Lancet Respir Med, 2026;14(5):443-452. PMID: 41887242.", "pmid": "41887242" }, { "type": "pubmed", "citation": "Rigatto MH, et al. \"Melatonin for prevention of acute kidney injury in patients treated with intravenous polymyxin B: a double-blind, placebo-controlled randomized clinical trial.\" Clin Microbiol Infect, 2023;29(5):623-628. PMID: 36586514.", "pmid": "36586514" }, { "type": "pubmed", "citation": "Zavascki AP, et al. \"Polymyxin B for the treatment of multidrug-resistant pathogens: a critical review.\" J Antimicrob Chemother, 2007;60(6):1206-15. PMID: 17878146.", "pmid": "17878146" }, { "type": "pubmed", "citation": "Crass RL, et al. \"Pharmacokinetics of Polymyxin B in Hospitalized Adults with Cystic Fibrosis.\" Antimicrob Agents Chemother, 2021;65(10):e0079221. PMID: 34252297.", "pmid": "34252297" }, { "type": "pubmed", "citation": "Cheng Y, et al. \"Inhaled alone versus inhaled plus intravenous polymyxin B for the treatment of pneumonia due to carbapenem-resistant gram-negative bacteria: A prospective randomized controlled trial.\" Int J Antimicrob Agents, 2025;65(5):107483. PMID: 40023452.", "pmid": "40023452" } ], "interactionCoverage": "none-found", "related": [ "daptomycin", "ll-37", "pexiganan" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-20", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "pralmorelin", "name": "Pralmorelin", "aliases": [ "GHRP-2", "KP-102", "Growth Hormone Releasing Peptide 2" ], "tier": "stub", "category": "growth-hormone", "subcategory": "growth hormone secretagogue", "class": "A synthetic growth hormone-releasing peptide (GHS-R1a agonist); the same molecule as GHRP-2.", "tagline": "The nonproprietary name for GHRP-2: a synthetic hexapeptide growth hormone secretagogue, approved in Japan as a diagnostic agent for growth hormone deficiency.", "oneLiner": "Pralmorelin is the nonproprietary name of GHRP-2 (D-Ala-D-2-Nal-Ala-Trp-D-Phe-Lys-NH2), a synthetic hexapeptide agonist of the ghrelin receptor (GHS-R1a) that releases growth hormone and is approved in Japan as a diagnostic agent.", "sequence": "D-Ala-D-2-Nal-Ala-Trp-D-Phe-Lys-NH2", "molecularFormula": "C45H55N9O6", "molecularWeight": 818.0, "halfLife": { "value": null, "unit": null, "range": "not reported in humans in the abstracts we hold", "notes": "In rats, plasma levels fell rapidly in two phases and 80% of an IV dose was recovered unchanged in bile within an hour (2005); in people, growth hormone peaked within 60 minutes of a 100 µg IV dose (2007). The earlier half-life figures on this site (about 1 hour here, 20 to 30 minutes on the pralmorelin entry) had no source." }, "fdaStatus": "not-approved-us", "approvalDetails": "Approved in Japan as a diagnostic agent for GH deficiency (GHRP test). Not FDA-approved in the US.", "mechanism": "Agonist at the growth hormone secretagogue receptor type 1a (GHS-R1a, later identified as the ghrelin receptor). Stimulates GH release from pituitary somatotrophs via a distinct mechanism from GHRH (Gq/11 → PLC → IP3 → Ca²⁺ release, vs. GHRH's Gs → cAMP pathway). Also modestly stimulates ACTH, cortisol, and prolactin.", "primaryUses": [ "GH deficiency diagnostic test (Japan)", "GH secretagogue research", "GHS-R pharmacology studies" ], "typicalDose": { "range": "100", "unit": "mcg", "frequency": "single IV bolus (diagnostic)", "route": "intravenous", "notes": "Diagnostic use: single 100 mcg IV bolus with GH sampling at 15, 30, 45, 60 minutes." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Bowers CY, et al. \"On the in vitro and in vivo activity of a new synthetic hexapeptide that acts on the pituitary to specifically release growth hormone.\" Endocrinology, 1984;114:1537-1545. PMID: 6714155.", "pmid": "6714155" } ], "interactionCoverage": "studied", "related": [ "ghrp-2", "ghrp-6", "hexarelin", "ghrelin", "mk-677" ], "lastReviewed": "2026-04-20", "publishedAt": "2026-04-20", "fdaApproved": false, "approvedElsewhere": "Japan (diagnostic use)", "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.2.4", "named": true, "wording": "GHRP-2 (pralmorelin)", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Being approved in Japan does not lift this: S2 naming is independent of approval status." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.2.4", "named": true, "wording": "GHRP-2 (pralmorelin)", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Being approved in Japan does not lift this: S2 naming is independent of approval status." } ], "moleculeClass": "peptide" }, { "id": "pramlintide", "name": "Pramlintide", "aliases": [ "Symlin", "AC137" ], "tier": "mid", "category": "metabolic", "subcategory": "amylin analog", "class": "A synthetic amylin analog with three proline substitutions to eliminate fibril formation, FDA-approved as an insulin adjunct in type 1 and type 2 diabetes.", "tagline": "The FDA-approved amylin analog (Symlin, 2005) — taken at mealtimes alongside insulin in T1D and T2D. The pharmacological proof-of-concept for amylin agonism that petrelintide and cagrilintide are now building on.", "oneLiner": "A synthetic analog of the β-cell peptide hormone amylin, engineered with three proline substitutions at positions 25, 28, and 29 to prevent the fibril formation that plagues native human amylin; co-secreted physiologically with insulin and acting to suppress glucagon, slow gastric emptying, and promote satiety — properties that have motivated the newer long-acting amylin analogs cagrilintide (CagriSema) and petrelintide.", "sequence": "KCNTATCATQRLANFLVHSSNNFGPILPPTNVGSNTY-NH2 (with Pro substitutions at 25, 28, 29; Cys2–Cys7 disulfide; C-terminal amide)", "molecularFormula": "C171H267N51O53S2", "molecularWeight": 3949.42, "halfLife": { "value": 48, "unit": "minutes", "range": "about 48 minutes in healthy individuals (label 12.3)", "source": { "type": "label", "ref": "Symlin (pramlintide acetate) prescribing information, boxed warning and sections 1, 2, 4, 5, 6, 12.1 and 12.3 (DailyMed SPL version 18, effective December 18, 2019; read October 1, 2026)" } }, "fdaStatus": "approved", "approvalDetails": "Symlin, NDA 021332, approved March 16, 2005, as an adjunct to mealtime insulin in type 1 and type 2 diabetes; Drugs@FDA lists every Symlin product as discontinued (read October 1, 2026).", "mechanism": "Binds the amylin receptor (a heterodimer of calcitonin receptor and a RAMP protein). Slows gastric emptying, suppresses post-prandial glucagon, and promotes satiety via area postrema signaling. The glucagon suppression and delayed glucose absorption blunt post-meal hyperglycemia, while the satiety effect produces modest weight loss in insulin-dependent patients who historically gain weight on insulin intensification.", "primaryUses": [ "Type 1 diabetes mellitus (mealtime insulin adjunct)", "Type 2 diabetes mellitus (mealtime insulin adjunct)" ], "typicalDose": { "range": "15-120", "unit": "mcg", "frequency": "before each major meal", "route": "subcutaneous", "notes": "Symlin label: cut mealtime insulin by 50% at initiation. Type 1: 15 mcg before major meals, increased in 15 mcg steps to 30 or 60 mcg. Type 2: 60 mcg, increased to 120 mcg. At least 3 days between titrations to limit nausea. Every US product is now discontinued." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Symlin (pramlintide acetate) prescribing information, boxed warning and sections 1, 2, 4, 5, 6, 12.1 and 12.3 (DailyMed SPL version 18, effective December 18, 2019; read October 1, 2026)." }, { "type": "pubmed", "citation": "Ratner RE, et al. \"Adjunctive therapy with the amylin analogue pramlintide leads to a combined improvement in glycemic and weight control in insulin-treated subjects with type 2 diabetes.\" Diabetes Technol Ther, 2002;4(1):51-61. PMID: 12017421.", "pmid": "12017421" }, { "type": "pubmed", "citation": "Nyholm B, et al. \"The amylin analog pramlintide improves glycemic control and reduces postprandial glucagon concentrations in patients with type 1 diabetes mellitus.\" Metabolism, 1999;48(7):935-41. PMID: 10421239.", "pmid": "10421239" }, { "type": "pubmed", "citation": "Haidar A, et al. \"A Novel Dual-Hormone Insulin-and-Pramlintide Artificial Pancreas for Type 1 Diabetes: A Randomized Controlled Crossover Trial.\" Diabetes Care, 2020;43(3):597-606. PMID: 31974099.", "pmid": "31974099" }, { "type": "pubmed", "citation": "Ghanizada H, et al. \"Amylin Analog Pramlintide Induces Migraine-like Attacks in Patients.\" Ann Neurol, 2021;89(6):1157-1171. PMID: 33772845.", "pmid": "33772845" }, { "type": "pubmed", "citation": "Sheehan A, et al. \"Pramlintide for post-bariatric hypoglycaemia.\" Diabetes Obes Metab, 2022;24(6):1021-1028. PMID: 35137513.", "pmid": "35137513" } ], "interactionCoverage": "partial", "related": [ "petrelintide", "cagrisema", "semaglutide" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide", "statusVerified": { "date": "2026-09-30", "source": "US FDA, Drugs@FDA (openFDA): Symlin, AstraZeneca, NDA 021332 — all products Discontinued. Approval stands; marketing has ended." } }, { "id": "prostamax", "name": "Prostamax", "aliases": [ "Prostagen", "Prostate peptide bioregulator", "KEDP tetrapeptide" ], "tier": "stub", "category": "longevity", "subcategory": "Khavinson prostate-derived peptide bioregulator", "class": "A prostate-derived short peptide bioregulator in the Khavinson framework, nominally associated with the synthetic tetrapeptide Lys-Glu-Asp-Pro (KEDP); marketed in Russia for prostate aging.", "tagline": "A Khavinson prostate bioregulator preparation marketed in Russia for prostate aging, with the synthetic KEDP tetrapeptide (Prostagen) as its characterized active fragment. Russian-language evidence base; no FDA/EMA status; no independent Western clinical replication.", "oneLiner": "A prostate-tissue-derived peptide bioregulator preparation in the Khavinson cytomedine series. The associated synthetic tetrapeptide is Lys-Glu-Asp-Pro (KEDP), variously marketed under the name Prostagen, claimed in Khavinson-group studies to modulate prostate-tissue gene expression and support benign prostate aging. As with the rest of the Khavinson short-peptide series, the evidence base consists of Russian-language studies from a single research network, and mechanistic claims should be regarded as preliminary.", "sequence": "Lys-Glu-Asp-Pro (KEDP, synthetic Prostagen)", "molecularFormula": "C18H30N6O8", "molecularWeight": 458.47, "halfLife": { "value": null, "unit": null, "range": "Not characterized in humans", "notes": "No published human pharmacokinetic data." }, "fdaStatus": "not-approved-us", "approvalDetails": "Not FDA- or EMA-approved. Sold in Russia and CIS markets as a nutraceutical supplement; the synthetic KEDP tetrapeptide (Prostagen) is sold as a research chemical in grey-market catalogs. No registered-medicine status in any Western jurisdiction.", "mechanism": "Proposed to modulate prostate-tissue gene expression in a \"tissue-specific\" Khavinson-framework manner. Mechanistic claims have not been independently validated in peer-reviewed Western literature. Speculative at the molecular level.", "primaryUses": [ "Benign prostatic aging support (Russian nutraceutical positioning)", "Post-prostatitis recovery support (Russian clinical use)" ], "typicalDose": { "range": "1–2 capsules", "unit": null, "frequency": "1–2 times daily in 20–30 day courses", "route": "oral", "notes": "Russian nutraceutical dosing. No controlled clinical evidence of efficacy." }, "evidenceLevel": "low", "sources": [ { "type": "review", "citation": "Khavinson VK, et al. \"Tetrapeptide Prostamax stimulates gene expression and protein synthesis in prostate tissue.\" Bull Exp Biol Med, 2010;149:354-356." }, { "type": "review", "citation": "Anisimov VN, Khavinson VK. \"Peptide bioregulation of aging: results and prospects.\" Biogerontology, 2010;11:139-149. PMID: 19830585.", "pmid": "19830585" } ], "interactionCoverage": "none-found", "related": [ "epithalon", "testagen", "pinealon" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": "", "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "protirelin", "name": "Protirelin", "aliases": [ "TRH", "thyrotropin-releasing hormone", "Thypinone", "Relefact TRH", "Thyrel TRH" ], "tier": "mid", "category": "growth-hormone", "subcategory": "TRH diagnostic / test peptide", "class": "Synthetic thyrotropin-releasing hormone — a pyroglutamyl-histidyl-prolinamide tripeptide released from the hypothalamus to stimulate pituitary TSH and prolactin secretion.", "tagline": "Synthetic thyrotropin-releasing hormone (pGlu-His-Pro-NH2), once FDA-approved as the pituitary diagnostics Thypinone (1976) and Thyrel TRH (1978), both now discontinued; tried experimentally in depression, ALS and preterm lung disease.", "oneLiner": "Synthetic thyrotropin-releasing hormone (TRH) — a pyroglutamyl-histidyl-prolinamide tripeptide that binds the TRH receptor on pituitary thyrotrophs and lactotrophs, stimulating TSH and prolactin release. Historically used as a diagnostic agent for TSH stimulation testing (assessment of secondary hypothyroidism, pituitary reserve, and atypical hyperthyroidism) and, much more rarely, for prolactin reserve testing. US commercial supply of protirelin (Thypinone / Relefact TRH / Thyrel TRH) has lapsed, and TRH testing has largely been replaced by sensitive third-generation TSH immunoassays. Remains available in some other markets. Included for reference as a canonical hypothalamic releasing peptide.", "sequence": "pGlu-His-Pro-NH2 (3 aa tripeptide)", "molecularFormula": "C16H22N6O4", "molecularWeight": 362.38, "halfLife": { "value": null, "unit": null, "range": "Not reported in the abstracts read", "notes": "The earlier '~2-5 minutes' had no source.", "source": { "type": "qualitative", "note": "a description with no figure; no half-life measurement is cited for it" } }, "fdaStatus": "discontinued", "approvalDetails": "FDA: Thypinone (Abbott, NDA 017638) approved November 5, 1976 and Thyrel TRH (Ferring, NDA 018087) approved July 18, 1978; both listed as discontinued (Drugs@FDA, read September 30, 2026). Not in EMA's register.", "mechanism": "Binds TRH receptor (TRHR) — a Gq-coupled receptor — on pituitary thyrotrophs to stimulate TSH release, and on lactotrophs to stimulate prolactin release. Effects are prompt (peak TSH at 20–30 minutes) and dose-dependent. In central (secondary) hypothyroidism, TSH response to TRH is blunted; in primary hypothyroidism, response is exaggerated.", "primaryUses": [ "Historical: TSH stimulation testing for secondary hypothyroidism and pituitary reserve", "Historical: prolactin reserve testing" ], "typicalDose": { "range": "200–500", "unit": "mcg", "frequency": "single diagnostic dose", "route": "intravenous bolus", "notes": "Historical adult diagnostic dose 500 mcg IV; serial TSH and prolactin sampling at 15, 30, and 60 minutes post-dose." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Garbutt JC, et al. \"Dose-response studies with protirelin.\" Arch Gen Psychiatry, 1994;51(11):875-83. PMID: 7944876.", "pmid": "7944876" }, { "type": "pubmed", "citation": "Marangell LB, et al. \"Effects of intrathecal thyrotropin-releasing hormone (protirelin) in refractory depressed patients.\" Arch Gen Psychiatry, 1997;54(3):214-22. PMID: 9075462.", "pmid": "9075462" }, { "type": "pubmed", "citation": "Knight DB, et al. \"A randomized, controlled trial of antepartum thyrotropin-releasing hormone and betamethasone in the prevention of respiratory disease in preterm infants.\" Am J Obstet Gynecol, 1994;171(1):11-6. PMID: 8030684.", "pmid": "8030684" }, { "type": "pubmed", "citation": "Gross I, et al. \"Is there a role for antenatal TRH therapy for the prevention of neonatal lung disease?.\" Semin Perinatol, 2001;25(6):406-16. PMID: 11778911.", "pmid": "11778911" }, { "type": "pubmed", "citation": "Zaloga GP, et al. \"Diagnostic dosages of protirelin (TRH) elevate BP by noncatecholamine mechanisms.\" Arch Intern Med, 1984;144(6):1149-52. PMID: 6428340.", "pmid": "6428340" }, { "type": "pubmed", "citation": "Miller SC, et al. \"Protirelin (thyrotropin-releasing hormone) in amyotrophic lateral sclerosis. The role of androgens.\" Arch Neurol, 1989;46(3):330-5. PMID: 2563937.", "pmid": "2563937" }, { "type": "fda", "citation": "FDA. Drugs@FDA (openFDA): Thypinone NDA 017638 (November 5, 1976) and Thyrel TRH NDA 018087 (July 18, 1978), both discontinued. Read September 30, 2026." }, { "type": "other", "citation": "European Medicines Agency. Medicines register: no entry for protirelin. Read September 30, 2026." } ], "interactionCoverage": "none-found", "related": [ "corticorelin", "gonadorelin", "sermorelin" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "A discontinued drug: S0's own examples include discontinued drugs." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "A discontinued drug: S0's own examples include discontinued drugs." } ], "moleculeClass": "peptide" }, { "id": "pt-141", "name": "PT-141", "aliases": [ "Bremelanotide", "Vyleesi", "PT141" ], "tier": "full", "category": "sexual-health", "subcategory": "melanocortin receptor agonist", "class": "Non-selective melanocortin receptor agonist derived from α-MSH; the label names MC1R and MC4R as most relevant at the approved dose.", "tagline": "An FDA-approved melanocortin agonist for acquired, generalized hypoactive sexual desire disorder in premenopausal women.", "oneLiner": "A 7-amino-acid cyclic lactam analog of α-melanocyte-stimulating hormone (α-MSH) that activates melanocortin receptors. Approved as Vyleesi; the label calls the mechanism by which it improves sexual desire unknown.", "sequence": "Ac-Nle-cyclic(Asp-His-D-Phe-Arg-Trp-Lys)-OH", "molecularFormula": "C50H68N14O10", "molecularWeight": 1025.2, "halfLife": { "value": 2.7, "unit": "hours", "range": "~2.7 hours (1.9–4.0)", "notes": "Vyleesi label: peak plasma level about 1 hour after injection (0.5–1); how long the effect lasts after a dose is unknown." }, "fdaStatus": "approved", "approvalDetails": "FDA-approved June 21, 2019 as Vyleesi (bremelanotide injection) for acquired, generalized hypoactive sexual desire disorder in premenopausal women. Developed by Palatin Technologies; FDA granted the 2019 approval to AMAG Pharmaceuticals, and the current US label (DailyMed, November 2025) lists Cosette Pharmaceuticals.", "mechanism": "Non-selective melanocortin receptor agonist. The label ranks its potency MC1R > MC4R > MC3R > MC5R > MC2R, names MC1R and MC4R as most relevant at the approved dose, and calls the mechanism by which it improves desire unknown. In female rats it increased solicitation behaviour through the medial preoptic area, possibly by releasing dopamine. Each dose transiently raises blood pressure and lowers heart rate; MC1R activity is the likely source of focal hyperpigmentation.", "primaryUses": [ "Hypoactive sexual desire disorder in premenopausal women (FDA-approved, Vyleesi)", "Erectile dysfunction (intranasal trials, 2004–2008; never approved)" ], "typicalDose": { "range": "1.75", "unit": "mg", "frequency": "as needed, ≥45 min before anticipated sexual activity", "route": "subcutaneous", "notes": "FDA-labeled dose (Vyleesi): no more than one dose in 24 hours; more than 8 doses a month is not recommended; stop after 8 weeks without improvement. Contraindicated in uncontrolled hypertension and known cardiovascular disease." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Vyleesi (bremelanotide injection) Prescribing Information. Cosette Pharmaceuticals, Inc. DailyMed, published November 18, 2025." }, { "type": "news-release", "citation": "U.S. Food and Drug Administration. \"FDA approves new treatment for hypoactive sexual desire disorder in premenopausal women.\" News release, June 21, 2019." }, { "type": "clinical-trial", "citation": "Kingsberg SA, et al. \"Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials.\" Obstet Gynecol, 2019;134(5):899-908. PMID: 31599840.", "pmid": "31599840" }, { "type": "pubmed", "citation": "Simon JA, et al. \"Long-Term Safety and Efficacy of Bremelanotide for Hypoactive Sexual Desire Disorder.\" Obstet Gynecol, 2019;134(5):909-917. PMID: 31599847.", "pmid": "31599847" }, { "type": "clinical-trial", "citation": "Clayton AH, et al. \"Bremelanotide for female sexual dysfunctions in premenopausal women: a randomized, placebo-controlled dose-finding trial.\" Womens Health (Lond), 2016;12(3):325-37. PMID: 27181790.", "pmid": "27181790" }, { "type": "pubmed", "citation": "Clayton AH, et al. \"Safety Profile of Bremelanotide Across the Clinical Development Program.\" J Womens Health (Larchmt), 2022;31(2):171-182. PMID: 35147466.", "pmid": "35147466" }, { "type": "pubmed", "citation": "White WB, et al. \"Usefulness of ambulatory blood pressure monitoring to assess the melanocortin receptor agonist bremelanotide.\" J Hypertens, 2017;35(4):761-768. PMID: 27977473.", "pmid": "27977473" }, { "type": "pubmed", "citation": "Diamond LE, et al. \"Double-blind, placebo-controlled evaluation of the safety, pharmacokinetic properties and pharmacodynamic effects of intranasal PT-141, a melanocortin receptor agonist, in healthy males and patients with mild-to-moderate erectile dysfunction.\" Int J Impot Res, 2004;16(1):51-9. PMID: 14963471.", "pmid": "14963471" }, { "type": "pubmed", "citation": "Safarinejad MR, et al. \"Salvage of sildenafil failures with bremelanotide: a randomized, double-blind, placebo controlled study.\" J Urol, 2008;179(3):1066-71. PMID: 18206919.", "pmid": "18206919" }, { "type": "pubmed", "citation": "Diamond LE, et al. \"An effect on the subjective sexual response in premenopausal women with sexual arousal disorder by bremelanotide (PT-141), a melanocortin receptor agonist.\" J Sex Med, 2006;3(4):628-638. PMID: 16839319.", "pmid": "16839319" }, { "type": "pubmed", "citation": "Clayton AH, et al. \"Phase I Randomized Placebo-controlled, Double-blind Study of the Safety and Tolerability of Bremelanotide Coadministered With Ethanol in Healthy Male and Female Participants.\" Clin Ther, 2017;39(3):514-526.e14. PMID: 28189361.", "pmid": "28189361" }, { "type": "review", "citation": "Spielmans GI. \"Re-Analyzing Phase III Bremelanotide Trials for \"Hypoactive Sexual Desire Disorder\" in Women.\" J Sex Res, 2021;58(9):1085-1105. PMID: 33678061.", "pmid": "33678061" }, { "type": "review", "citation": "Spielmans GI, et al. \"Small Effects, Questionable Outcomes: Bremelanotide for Hypoactive Sexual Desire Disorder.\" J Sex Res, 2024;61(4):540-561. PMID: 36809187.", "pmid": "36809187" }, { "type": "review", "citation": "Mintzes B, et al. \"Bremelanotide and flibanserin for low sexual desire in women: the fallacy of regulatory precedent.\" Drug Ther Bull, 2021;59(12):185-188. PMID: 34642243.", "pmid": "34642243" }, { "type": "review", "citation": "Cipriani S, et al. \"An evaluation of bremelanotide injection for the treatment of hypoactive sexual desire disorder.\" Expert Opin Pharmacother, 2023;24(1):15-21. PMID: 36242769.", "pmid": "36242769" }, { "type": "review", "citation": "Dhillon S, et al. \"Bremelanotide: First Approval.\" Drugs, 2019;79(14):1599-1606. PMID: 31429064.", "pmid": "31429064" }, { "type": "pubmed", "citation": "Pfaus J, et al. \"Bremelanotide: an overview of preclinical CNS effects on female sexual function.\" J Sex Med, 2007;4 Suppl 4:269-79. PMID: 17958619.", "pmid": "17958619" }, { "type": "pubmed", "citation": "Borland JM, et al. \"Female Syrian hamster analyses of bremelanotide, a US FDA approved drug for the treatment of female hypoactive sexual desire disorder.\" Neuropharmacology, 2025;267:110299. PMID: 39793696.", "pmid": "39793696" }, { "type": "pubmed", "citation": "Kingsberg SA, et al. \"Failure of a Meta-analysis: A Commentary on Glen Spielmans's \"Re-Analyzing Phase III Bremelanotide Trials for 'Hypoactive Sexual Desire Disorder in Women'\".\" J Sex Res, 2021;58(9):1106-1107. PMID: 33835907.", "pmid": "33835907" } ], "interactionCoverage": "full", "related": [ "melanotan-ii", "afamelanotide" ], "lastReviewed": "2026-09-26", "publishedAt": "2026-04-18", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "pyy", "name": "Peptide YY", "aliases": [ "PYY", "PYY3-36", "Peptide Tyrosine Tyrosine" ], "tier": "mid", "category": "metabolic", "subcategory": "endogenous gut hormone", "class": "A 36-amino-acid gut hormone released postprandially by L-cells, named for its flanking tyrosine residues, functioning as a satiety signal.", "tagline": "The postprandial 'stop eating' signal — an endogenous satiety peptide that reduces appetite via the Y2 receptor, and a pharmacological target for next-generation obesity drugs.", "oneLiner": "A 36-amino-acid peptide released from intestinal L-cells after meals, whose truncated form PYY3-36 acts as a potent satiety factor via hypothalamic Y2 receptors.", "sequence": "YPIKPEAPGEDASPEELNRYYASLRHYLNLVTRQRY-NH2", "molecularFormula": "C178H264N48O56S", "molecularWeight": 4049.7, "halfLife": { "value": null, "unit": null, "range": "not reported in the sources read", "source": { "type": "none", "note": "searched PubMed on October 1, 2026; no human half-life figure in the sources read" } }, "fdaStatus": "research-only", "approvalDetails": "Not approved as a drug; no application appears in Drugs@FDA (read October 1, 2026). It has been given to people only by infusion in research.", "mechanism": "PYY3-36 selectively activates the Y2 receptor, a presynaptic inhibitory GPCR on NPY/AgRP neurons in the arcuate nucleus. Inhibits orexigenic drive, slows gastric emptying, and reduces intestinal motility. Released proportionally to caloric load. Levels are reduced in obesity, suggesting a potential therapeutic role.", "primaryUses": [ "Satiety signaling research", "Obesity pathophysiology studies", "Gut-brain axis research", "Bariatric surgery mechanism studies" ], "typicalDose": { "range": null, "unit": null, "frequency": null, "route": null, "notes": "Not a medicine. Human studies infuse PYY3-36 intravenously, typically at 0.8 pmol/kg/min over about 150 minutes." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Schmidt JB, et al. \"Effects of PYY3-36 and GLP-1 on energy intake, energy expenditure, and appetite in overweight men.\" Am J Physiol Endocrinol Metab, 2014;306(11):E1248-56. PMID: 24735885.", "pmid": "24735885" }, { "type": "pubmed", "citation": "Field BC, et al. \"PYY3-36 and oxyntomodulin can be additive in their effect on food intake in overweight and obese humans.\" Diabetes, 2010;59(7):1635-9. PMID: 20357366.", "pmid": "20357366" }, { "type": "pubmed", "citation": "Witte AB, et al. \"Differential effect of PYY1-36 and PYY3-36 on gastric emptying in man.\" Regul Pept, 2009;158(1-3):57-62. PMID: 19651163.", "pmid": "19651163" }, { "type": "pubmed", "citation": "Batterham RL, et al. \"Gut hormone PYY(3-36) physiologically inhibits food intake.\" Nature, 2002;418(6898):650-4. PMID: 12167864.", "pmid": "12167864" }, { "type": "pubmed", "citation": "Karra E, et al. \"The role of gut hormones in the regulation of body weight and energy homeostasis.\" Mol Cell Endocrinol, 2010;316(2):120-8. PMID: 19563862.", "pmid": "19563862" } ], "interactionCoverage": "unreviewed", "related": [ "semaglutide", "tirzepatide", "glucagon" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-20", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "relamorelin", "name": "Relamorelin", "aliases": [ "RM-131", "BIM-28131" ], "tier": "stub", "category": "pipeline", "subcategory": "pentapeptide ghrelin / motilin-pathway agonist", "class": "A synthetic pentapeptide ghrelin receptor agonist with prokinetic activity, developed principally for diabetic gastroparesis and other GI motility disorders.", "tagline": "Motus Therapeutics' (formerly Rhythm, then Allergan) ghrelin agonist pentapeptide — Phase 2b results in diabetic gastroparesis were positive, Phase 3 development paused following Allergan's divestiture; status ambiguous as of 2026.", "oneLiner": "A synthetic pentapeptide ghrelin receptor (GHS-R1a) agonist with accentuated prokinetic activity, developed primarily for diabetic gastroparesis. Phase 2b trials in diabetic gastroparesis showed meaningful reductions in core symptoms (vomiting, nausea, abdominal pain, bloating, early satiety) and improvements in gastric emptying. Development was licensed from Ipsen to Rhythm Pharmaceuticals (which later spun out the metabolic program as Motus Therapeutics), then acquired by Allergan. Following Allergan's 2020 acquisition by AbbVie, Phase 3 development appeared to stall; status ambiguous as of 2026.", "sequence": "Synthetic pentapeptide (2-amino-isobutyryl-D-Trp-D-Phe-D-Trp-Leu-NH2 with proprietary modifications)", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": "hours", "range": "short", "notes": "Subcutaneous administration, twice-daily dosing in Phase 2." }, "fdaStatus": "clinical-trials", "approvalDetails": "Not approved. Phase 2b completed in diabetic gastroparesis (positive outcome 2017). Development program transferred Ipsen → Rhythm → Motus → Allergan → AbbVie; Phase 3 plans announced 2018 but program status since the 2020 AbbVie acquisition has not been publicly clarified.", "mechanism": "Agonism at the ghrelin receptor (GHS-R1a), with an in-vivo profile biased toward gastrointestinal prokinetic effects (accelerated gastric emptying via vagal afferent signaling and enteric neural pathways) rather than toward pituitary GH release. Clinical effects in gastroparesis appear mediated principally through this motility action.", "primaryUses": [ "Diabetic gastroparesis (investigational)", "Chronic idiopathic constipation (investigational)" ], "typicalDose": { "range": "10–100", "unit": "mcg twice daily", "frequency": "twice daily (Phase 2 protocol)", "route": "subcutaneous", "notes": "Investigational dosing only." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "Camilleri M, et al. \"Efficacy and Safety of Relamorelin in Diabetics With Symptoms of Gastroparesis: A Randomized, Placebo-Controlled Study.\" Gastroenterology, 2017;153:1240-1250. PMID: 28760384.", "pmid": "28760384" }, { "type": "manufacturer", "citation": "Allergan. 2018 investor communications regarding relamorelin gastroparesis Phase 3 plans." } ], "interactionCoverage": "none-found", "related": [ "anamorelin", "mk-677", "ghrp-2" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.2.4", "named": false, "wording": "growth hormone secretagogues (GHS) and their mimetics", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "A ghrelin-receptor agonist, the receptor the named secretagogues act on." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.2.4", "named": false, "wording": "growth hormone secretagogues (GHS) and their mimetics", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "A ghrelin-receptor agonist, the receptor the named secretagogues act on." } ], "moleculeClass": "peptide" }, { "id": "relugolix", "name": "Relugolix", "aliases": [ "Orgovyx", "Relumina", "TAK-385" ], "tier": "stub", "category": "sexual-health", "subcategory": "GnRH antagonist (oral)", "class": "An oral non-peptide GnRH receptor antagonist for prostate cancer and uterine fibroids, providing rapid and sustained testosterone or estrogen suppression.", "tagline": "The oral alternative to Lupron — a once-daily pill that suppresses testosterone to castrate levels for prostate cancer without the flare, injection, or cold-chain requirements of injectable GnRH agonists.", "oneLiner": "A non-peptide oral GnRH receptor antagonist achieving castrate testosterone levels within days (vs. weeks for leuprolide), FDA-approved for advanced prostate cancer and uterine fibroids.", "sequence": "Non-peptide small molecule (GnRH receptor antagonist)", "molecularFormula": "C29H27F2N7O5S", "molecularWeight": 623.6, "halfLife": { "value": 60, "unit": "hours", "range": "~25–60 hours (effective)", "notes": "Terminal half-life supports once-daily dosing. Achieves castrate testosterone (<50 ng/dL) by Day 4 in 56% of patients and Day 15 in 99%." }, "fdaStatus": "approved", "approvalDetails": "FDA-approved in 2020 (Orgovyx, Myovant Sciences) for advanced prostate cancer. Also approved in combination with estradiol/norethindrone (Myfembree) for uterine fibroids (2021). Approved in Japan as Relumina for uterine fibroids.", "mechanism": "Competitive antagonist at the pituitary GnRH receptor. Rapidly suppresses LH and FSH without the initial agonist flare seen with GnRH agonists. In prostate cancer, this achieves medical castration. Unlike depot GnRH agonists, testosterone recovery occurs within weeks of discontinuation.", "primaryUses": [ "Advanced prostate cancer (androgen deprivation therapy)", "Uterine fibroids (as Myfembree combination)", "Endometriosis (Japan)" ], "typicalDose": { "range": "120", "unit": "mg", "frequency": "once daily (after 360 mg loading dose on Day 1)", "route": "oral", "notes": "Loading dose of 360 mg on Day 1 accelerates testosterone suppression. Take without food or with a low-fat meal." }, "evidenceLevel": "high", "sources": [ { "type": "clinical-trial", "citation": "Shore ND, et al. \"Oral relugolix for androgen-deprivation therapy in advanced prostate cancer (HERO).\" N Engl J Med, 2020;382:2187-2196. PMID: 32469183.", "pmid": "32469183" }, { "type": "fda-pi", "citation": "Orgovyx (relugolix) Prescribing Information. Myovant Sciences." } ], "interactionCoverage": "label", "related": [ "leuprolide", "elagolix", "degarelix", "goserelin" ], "lastReviewed": "2026-04-20", "publishedAt": "2026-04-20", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "A GnRH antagonist: S2.2.1 covers GnRH and its agonist analogues, not antagonists." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "A GnRH antagonist: S2.2.1 covers GnRH and its agonist analogues, not antagonists." } ], "moleculeClass": "small-molecule", "moleculeClassBasis": "non-peptide" }, { "id": "retatrutide", "name": "Retatrutide", "aliases": [ "LY3437943", "Triple-G" ], "tier": "full", "category": "metabolic", "subcategory": "GLP-1/GIP/glucagon triple agonist", "class": "Investigational triple agonist at GLP-1, GIP, and glucagon receptors.", "tagline": "An investigational triple hormone agonist that produced ~24% weight loss at 48 weeks in Phase 2 — the largest in any single-agent obesity trial to date.", "oneLiner": "A synthetic peptide agonist at GLP-1, GIP, and glucagon receptors, with glucagon agonism adding an energy-expenditure component on top of appetite suppression.", "sequence": null, "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": 6, "unit": "days", "range": "~6 days", "notes": "Weekly dosing supported by pharmacokinetic profile." }, "fdaStatus": "clinical-trials", "approvalDetails": "Investigational. Phase 3 TRIUMPH-1 and TRIUMPH-2 published in 2026. Developed by Eli Lilly, which plans a US Biologics License Application in the first quarter of 2027.", "mechanism": "Triple agonism at GLP-1, GIP, and glucagon receptors. GLP-1 and GIP contribute insulin-sensitization and appetite suppression; glucagon agonism adds thermogenic effects and increased energy expenditure, producing a compound effect on weight loss. The glucagon component requires careful dose titration to avoid hyperglycemia.", "primaryUses": [ "Obesity (Phase 3)", "Type 2 diabetes (Phase 3)", "MASH / liver disease (Phase 2)" ], "typicalDose": { "range": "1–12", "unit": "mg", "frequency": "weekly", "route": "subcutaneous", "notes": "Phase 3 used 4, 9 or 12 mg weekly; phase 2 used 0.5 to 12 mg." }, "evidenceLevel": "medium", "sources": [ { "type": "clinical-trial", "citation": "Jastreboff AM, et al. \"Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial.\" N Engl J Med, 2023;389:514-526. PMID: 37366315.", "pmid": "37366315" }, { "type": "clinical-trial", "citation": "Rosenstock J, et al. \"Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA.\" Lancet, 2023;402(10401):529-544. PMID: 37385280.", "pmid": "37385280" }, { "type": "clinical-trial", "citation": "ClinicalTrials.gov NCT05929066 (TRIUMPH-1, Phase 3 obesity trial)." }, { "type": "pubmed", "citation": "Coskun T, et al. \"Effects of retatrutide on body composition in people with type 2 diabetes: a substudy of a phase 2, double-blind, parallel-group, placebo-controlled, randomised trial.\" Lancet Diabetes Endocrinol, 2025;13(8):674-684. PMID: 40609566.", "pmid": "40609566" }, { "type": "pubmed", "citation": "Sanyal AJ, et al. \"Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial.\" Nat Med, 2024;30(7):2037-2048. PMID: 38858523.", "pmid": "38858523" }, { "type": "pubmed", "citation": "Urva S, et al. \"LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial.\" Lancet, 2022;400(10366):1869-1881. PMID: 36354040.", "pmid": "36354040" }, { "type": "pubmed", "citation": "Coskun T, et al. \"LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept.\" Cell Metab, 2022;34(9):1234-1247.e9. PMID: 35985340.", "pmid": "35985340" }, { "type": "pubmed", "citation": "Jastreboff AM, et al. \"Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity.\" N Engl J Med, 2026;. PMID: 42814954.", "pmid": "42814954" }, { "type": "pubmed", "citation": "Bellido V, et al. \"Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trial.\" Lancet, 2026;. PMID: 42810372.", "pmid": "42810372" }, { "type": "other", "citation": "Eli Lilly and Company. \"Lilly's triple agonist, retatrutide, successful in two additional Phase 3 obesity trials, delivering significant improvements in weight and A1C.\" Investor news release, July 23, 2026 (read September 30, 2026)." } ], "interactionCoverage": "partial", "related": [ "tirzepatide", "semaglutide", "liraglutide" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." } ], "moleculeClass": "peptide" }, { "id": "rigin", "name": "Rigin", "aliases": [ "Palmitoyl Tetrapeptide-7", "Pal-Gly-Gln-Pro-Arg" ], "tier": "stub", "category": "cosmetic", "subcategory": "topical cosmetic peptide (anti-inflammatory)", "class": "A palmitoylated tetrapeptide developed as a topical cosmetic ingredient with anti-inflammatory claims targeting glycation and IL-6-driven skin inflammation.", "tagline": "A cosmetic tetrapeptide marketed as an anti-inflammatory \"Matrixyl companion\" — claimed to reduce IL-6 and dampen glycation-driven skin aging; co-formulated with Pal-KTTKS + Pal-GHK in Matrixyl 3000+Rigin products.", "oneLiner": "Palmitoyl tetrapeptide-7, a palmitoylated tetrapeptide developed by Sederma as a cosmetic ingredient claimed to reduce cutaneous IL-6 expression and dampen inflammation associated with glycation-driven skin aging; commonly co-formulated with Pal-KTTKS and Pal-GHK.", "sequence": "Pal-Gly-Gln-Pro-Arg", "molecularFormula": "C38H69N7O7", "molecularWeight": 736, "halfLife": { "value": null, "unit": null, "range": "topical only", "notes": "Systemic absorption from topical cosmetic formulations is minimal." }, "fdaStatus": "research-only", "approvalDetails": "Cosmetic ingredient; not a drug.", "mechanism": "Claimed by the manufacturer to modulate inflammatory cytokine expression (particularly IL-6) in keratinocytes and fibroblasts in response to glycation and UV damage. Independent mechanistic replication is limited; most evidence comes from Sederma in-house studies.", "primaryUses": [ "Topical cosmetic anti-aging formulations (anti-inflammatory, anti-glycation)" ], "typicalDose": { "range": "3–5", "unit": "% (topical formulation)", "frequency": "twice daily", "route": "topical", "notes": "Cosmetic concentrations." }, "evidenceLevel": "low", "sources": [ { "type": "manufacturer", "citation": "Sederma. \"Rigin technical data sheet and cosmetic ingredient profile.\"" } ], "interactionCoverage": "unreviewed", "related": [ "matrixyl", "pal-ghk", "argireline" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." } ], "moleculeClass": "peptide" }, { "id": "romiplostim", "name": "Romiplostim", "aliases": [ "Nplate", "AMG 531", "TPO mimetic peptibody" ], "tier": "mid", "category": "immune", "subcategory": "Thrombopoietin receptor agonist", "class": "Romiplostim is a peptide-Fc fusion protein ('peptibody') that mimics thrombopoietin to stimulate platelet production — an elegant example of peptide-antibody hybrid engineering.", "tagline": "A peptibody that boosts platelet production — an Fc-fused peptide mimicking thrombopoietin, FDA-approved for immune thrombocytopenia.", "oneLiner": "A recombinant peptide-Fc fusion protein containing four copies of a 14-amino-acid TPO-mimetic peptide fused to an IgG1 Fc domain, FDA-approved for immune thrombocytopenia (ITP).", "sequence": "IEGPTLRQWLAARA-x4 (four copies fused to Fc domain)", "molecularFormula": "Fusion protein (~59 kDa)", "molecularWeight": 59000, "halfLife": { "value": null, "unit": null, "range": "not reported in the sources read", "source": { "type": "none", "note": "searched PubMed on October 1, 2026; no human half-life figure in the sources read" } }, "fdaStatus": "approved", "approvalDetails": "Nplate, BLA 125268, approved August 22, 2008. Indicated for thrombocytopenia in adults with immune thrombocytopenia who responded insufficiently to corticosteroids, immunoglobulins or splenectomy, in children one year and older with ITP for at least six months, and as a single 10 mcg/kg dose for people acutely exposed to myelosuppressive doses of radiation (Drugs@FDA and the label, read October 1, 2026).", "mechanism": "Four TPO-mimetic peptides bind c-Mpl (TPO receptor) on megakaryocyte progenitors, triggering JAK2/STAT5 and MAPK signaling to promote platelet production. Fc domain provides extended half-life via FcRn recycling. No homology with endogenous TPO.", "primaryUses": [ "Chronic immune thrombocytopenia (FDA-approved)", "ITP refractory to corticosteroids, IVIG, or splenectomy" ], "typicalDose": { "range": "1-10", "unit": "mcg/kg", "frequency": "once weekly in ITP; a single dose after radiation exposure", "route": "subcutaneous", "notes": "Nplate label: 1 mcg/kg once weekly subcutaneously in immune thrombocytopenia, adjusted to platelet response; for acute exposure to myelosuppressive doses of radiation, a single 10 mcg/kg dose as soon as possible after exposure." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Nplate (romiplostim) prescribing information, sections 1 and 2 (DailyMed SPL version 162, effective June 23, 2026; read October 1, 2026)." }, { "type": "pubmed", "citation": "Kuter DJ, et al. \"Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial.\" Lancet, 2008;371(9610):395-403. PMID: 18242413.", "pmid": "18242413" }, { "type": "pubmed", "citation": "Al-Samkari H, et al. \"Romiplostim versus Placebo for Chemotherapy-Induced Thrombocytopenia.\" N Engl J Med, 2026;394(11):1061-1073. PMID: 41812193.", "pmid": "41812193" }, { "type": "pubmed", "citation": "Jang JH, et al. \"Efficacy and safety of romiplostim in refractory aplastic anaemia: a Phase II/III, multicentre, open-label study.\" Br J Haematol, 2021;192(1):190-199. PMID: 33152120.", "pmid": "33152120" }, { "type": "pubmed", "citation": "Mitani K, et al. \"Long-term efficacy and safety of romiplostim in refractory aplastic anemia: follow-up of a phase 2/3 study.\" Blood Adv, 2024;8(6):1415-1419. PMID: 38134300.", "pmid": "38134300" }, { "type": "pubmed", "citation": "Peffault de Latour R, et al. \"Romiplostim in patients undergoing hematopoietic stem cell transplantation: results of a phase 1/2 multicenter trial.\" Blood, 2020;135(3):227-229. PMID: 31805185.", "pmid": "31805185" } ], "interactionCoverage": "label", "related": [ "thymosin-alpha-1", "thymopentin", "erythropoietin" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-21", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "protein", "moleculeClassBasis": "fusion protein" }, { "id": "rusfertide", "name": "Rusfertide", "aliases": [ "Mimrylo", "PTG-300" ], "tier": "mid", "category": "metabolic", "subcategory": "Hepcidin mimetic (FDA-approved)", "class": "A synthetic peptide mimetic of hepcidin, the hormone that controls iron trafficking, which binds ferroportin and restricts the iron available for making red blood cells.", "tagline": "The first hepcidin mimetic approved anywhere: it controls polycythaemia vera by starving red-cell production of iron, replacing repeated phlebotomy.", "oneLiner": "A synthetic hepcidin mimetic that binds ferroportin and withholds iron from the bone marrow, approved in 2026 as Mimrylo for erythrocytosis in polycythaemia vera.", "molecularFormula": "C114H181N27O28S2", "molecularWeight": 2442.0, "halfLife": { "value": 28.6, "unit": "hours", "range": "28.6 ± 11.3 hours (mean plasma elimination)", "source": { "type": "label", "ref": "Mimrylo prescribing information, section 12.3 (DailyMed version 2, effective August 28, 2026; read September 30, 2026)" } }, "fdaStatus": "approved", "fdaApproved": true, "approvedElsewhere": null, "approvalDetails": "FDA-approved as Mimrylo (rusfertide) for the treatment of erythrocytosis in adults with polycythaemia vera. Drugs@FDA lists NDA 220605, Takeda Pharmaceuticals America, as a prescription powder in four vial strengths (9.5, 28, 41 and 54 mg base). The label starts at 19 mg subcutaneously once a week over a 9.5 to 108 mg range; doses above 54 mg need two injections and doses above 82 mg are given on separate days.", "statusVerified": { "date": "2026-09-30", "source": "US FDA, Drugs@FDA (openFDA): MIMRYLO (rusfertide), Takeda, NDA 220605, prescription, powder in 9.5, 28, 41 and 54 mg base vials; label read on DailyMed (version 2, effective August 28, 2026)." }, "mechanism": "Hepcidin is the master regulator of iron trafficking: it binds ferroportin, the only known cellular iron exporter, and causes its degradation, so iron stays inside enterocytes and macrophages instead of entering plasma. Rusfertide mimics that, lowering transferrin saturation and the iron supply the marrow needs to make red cells. In polycythaemia vera, where a JAK2-driven clone overproduces erythrocytes, restricting iron limits erythropoiesis without targeting the clone.", "moleculeClass": "peptide", "evidenceLevel": "high", "interactionCoverage": "label", "typicalDose": { "range": "19", "unit": "mg", "frequency": "once weekly", "route": "subcutaneous", "notes": "Label starting dose 19 mg weekly, adjusted within a 9.5-108 mg weekly range by response and safety." }, "primaryUses": [ "Erythrocytosis in adults with polycythaemia vera (US label)" ], "related": [ "erythropoietin", "ara-290", "romiplostim" ], "publishedAt": "2026-09-30", "lastReviewed": "2026-09-30", "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-30" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-30" } ], "sources": [ { "type": "fda-pi", "citation": "Mimrylo (rusfertide) for injection Prescribing Information, sections 1 and 2. Takeda Pharmaceuticals America (DailyMed version 2, effective August 28, 2026; read September 30, 2026)." }, { "type": "pubmed", "citation": "Kremyanskaya M, et al. \"Rusfertide, a Hepcidin Mimetic, for Control of Erythrocytosis in Polycythemia Vera.\" N Engl J Med, 2024;390(8):723-735. PMID: 38381675.", "pmid": "38381675" }, { "type": "pubmed", "citation": "Chew LP, et al. \"Rusfertide rapidly decreases hematocrit in patients with suboptimally controlled polycythemia vera.\" Leuk Res, 2025;159:108132. PMID: 41175501.", "pmid": "41175501" }, { "type": "pubmed", "citation": "Kowdley KV, et al. \"Rusfertide for the treatment of iron overload in HFE-related haemochromatosis: an open-label, multicentre, proof-of-concept phase 2 trial.\" Lancet Gastroenterol Hepatol, 2023;8(12):1118-1128. PMID: 37863080.", "pmid": "37863080" }, { "type": "pubmed", "citation": "Modi NB, et al. \"Pharmacokinetics and Pharmacodynamics of Rusfertide, a Hepcidin Mimetic, Following Subcutaneous Administration of a Lyophilized Powder Formulation in Healthy Volunteers.\" Drugs R D, 2024;24(4):539-552. PMID: 39546273.", "pmid": "39546273" }, { "type": "pubmed", "citation": "Modi NB, et al. \"Evaluation of Rusfertide, a Hepcidin Mimetic, on Cardiac Repolarization: A Randomized, Placebo- and Positive-Controlled Crossover Thorough QT Study in Healthy Participants.\" Clin Ther, 2025;47(11):1043-1052. PMID: 41033871.", "pmid": "41033871" }, { "type": "other", "citation": "US FDA, Drugs@FDA (openFDA): MIMRYLO (rusfertide), Takeda, NDA 220605, prescription, powder in 9.5, 28, 41 and 54 mg base vials. Read September 30, 2026." } ] }, { "id": "secretin", "name": "Secretin", "aliases": [ "SCT", "Human secretin" ], "tier": "mid", "category": "metabolic", "subcategory": "Endogenous gut hormone", "class": "Secretin holds a unique place in peptide history — it was the first hormone ever discovered (1902), establishing the concept that chemical messengers could coordinate distant organ function.", "tagline": "The first hormone ever discovered — a 27-amino-acid gut peptide that stimulates pancreatic bicarbonate secretion and opened the entire field of endocrinology in 1902.", "oneLiner": "A 27-amino-acid peptide released by S-cells of the duodenum in response to gastric acid that stimulates pancreatic bicarbonate and bile secretion, inhibits gastrin, and is FDA-approved as a diagnostic agent for pancreatic function and gastrinoma.", "sequence": "HSDGTFTSELSRLREGARLQRLLQGLV-amide", "molecularFormula": "C130H220N44O39", "molecularWeight": 3055.5, "halfLife": { "value": 45, "unit": "minutes", "range": "45 minutes for synthetic human secretin; plasma levels back to baseline within 90 to 120 minutes", "source": { "type": "label", "ref": "ChiRhoStim (human secretin) prescribing information, sections 1, 2, 5 and 12.3 (DailyMed SPL effective October 8, 2025; read October 1, 2026)" } }, "fdaStatus": "approved", "approvalDetails": "ChiRhoStim (human secretin), NDA 021256, approved April 9, 2004 (Drugs@FDA, read October 1, 2026), as a diagnostic agent for pancreatic function testing, gastrinoma diagnosis and identifying the ampulla of Vater during ERCP. It is not approved to treat anything.", "mechanism": "Binds the secretin receptor (SCTR), a class B GPCR coupled to Gs/adenylyl cyclase/cAMP. In pancreatic duct cells, stimulates bicarbonate and water secretion. In the stomach, inhibits gastrin release. In the liver, stimulates bile flow.", "primaryUses": [ "Endogenous pancreatic bicarbonate secretion", "Diagnostic: secretin stimulation test for gastrinoma", "Diagnostic: pancreatic function testing", "Historical significance: first hormone ever identified (1902)" ], "typicalDose": { "range": "0.2-0.4", "unit": "mcg/kg", "frequency": "single diagnostic dose", "route": "intravenous over 1 minute", "notes": "ChiRhoStim label: 0.2 mcg/kg for pancreatic function testing and for ERCP, 0.4 mcg/kg for the gastrinoma test." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "ChiRhoStim (human secretin) prescribing information, sections 1, 2, 5 and 12.3 (DailyMed SPL effective October 8, 2025; read October 1, 2026)." }, { "type": "pubmed", "citation": "Sun L, et al. \"Secretin modulates appetite via brown adipose tissue-brain axis.\" Eur J Nucl Med Mol Imaging, 2023;50(6):1597-1606. PMID: 36764966.", "pmid": "36764966" }, { "type": "pubmed", "citation": "Laurila S, et al. \"Novel effects of the gastrointestinal hormone secretin on cardiac metabolism and renal function.\" Am J Physiol Endocrinol Metab, 2022;322(1):E54-E62. PMID: 34806426.", "pmid": "34806426" }, { "type": "pubmed", "citation": "Sheitman BB, et al. \"Secretin for refractory schizophrenia.\" Schizophr Res, 2004;66(2-3):177-81. PMID: 15061251.", "pmid": "15061251" }, { "type": "pubmed", "citation": "Honomichl RD, et al. \"Secretin and sleep in children with autism.\" Child Psychiatry Hum Dev, 2002;33(2):107-23. PMID: 12462350.", "pmid": "12462350" }, { "type": "pubmed", "citation": "Bayliss WM, et al. \"The mechanism of pancreatic secretion.\" J Physiol, 1902;28(5):325-53. PMID: 16992627.", "pmid": "16992627" }, { "type": "pubmed", "citation": "Afroze S, et al. \"The physiological roles of secretin and its receptor.\" Ann Transl Med, 2013;1(3):29. PMID: 25332973.", "pmid": "25332973" } ], "interactionCoverage": "label", "related": [ "cholecystokinin", "glucagon", "vip", "glp-2" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-21", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "selank", "name": "Selank", "aliases": [ "TP-7", "threonyl-lysyl-prolyl-arginyl-prolyl-glycyl-proline" ], "tier": "full", "category": "cognitive", "subcategory": "tuftsin-derived anxiolytic peptide", "class": "A synthetic heptapeptide analog of the endogenous immunomodulatory peptide tuftsin, developed in Russia as a non-benzodiazepine anxiolytic.", "tagline": "A Russian nasal anxiolytic built from the immune peptide tuftsin; its human evidence is small Russian trials that compare it with benzodiazepines, not placebo.", "oneLiner": "A 7-amino-acid synthetic peptide analog of tuftsin with C-terminal PGP extension for protease resistance, developed at the Institute of Molecular Genetics (Moscow) as a non-sedating anxiolytic that modulates GABAergic tone.", "sequence": "Thr-Lys-Pro-Arg-Pro-Gly-Pro", "molecularFormula": "C33H57N11O9", "molecularWeight": 751.88, "halfLife": { "value": null, "unit": null, "range": "not measured in humans", "notes": "No human half-life appears in the abstracts we hold. In rats, tritium-labelled selank given by several routes reached the brain best when given nasally and accumulated in stomach tissue (Ashmarin 2008). The '~10 minutes' given here before had no source." }, "fdaStatus": "not-approved-us", "approvalDetails": "Approved in Russia for generalized anxiety disorder and adjustment disorders. Not approved by the FDA or EMA.", "mechanism": "Modulates GABA-A receptor sensitivity and enkephalin degradation without directly binding the benzodiazepine site. Upregulates expression of genes involved in inflammation, immune response, and neurogenesis. Has demonstrated anxiolytic activity comparable to diazepam in rodent models without the sedation, tolerance, or withdrawal associated with benzodiazepines, and without the serotonin-mediated side effects of SSRIs.", "primaryUses": [ "Generalized anxiety disorder (Russian approval)", "Adjustment disorders", "Cognitive performance under stress", "Research on non-benzodiazepine anxiolytic mechanisms" ], "typicalDose": { "range": "400–900", "unit": "mcg", "frequency": "2–3 times daily", "route": "intranasal", "notes": "Russian clinical dosing: 0.15% solution, 2–3 drops per nostril, 2–3 times daily for 10–14 days." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "Zozulia AA, et al. \"[Efficacy and possible mechanisms of action of a new peptide anxiolytic selank in the therapy of generalized anxiety disorders and neurasthenia].\" Zh Nevrol Psikhiatr Im S S Korsakova, 2008;108(4):38-48. PMID: 18454096.", "pmid": "18454096" }, { "type": "pubmed", "citation": "Medvedev VE, et al. \"[A comparison of the anxiolytic effect and tolerability of selank and phenazepam in the treatment of anxiety disorders].\" Zh Nevrol Psikhiatr Im S S Korsakova, 2014;114(7):17-22. PMID: 25176261.", "pmid": "25176261" }, { "type": "pubmed", "citation": "Medvedev VE, et al. \"[Optimization of the treatment of anxiety disorders with selank].\" Zh Nevrol Psikhiatr Im S S Korsakova, 2015;115(6):33-40. PMID: 26356395.", "pmid": "26356395" }, { "type": "pubmed", "citation": "Uchakina ON, et al. \"[Immunomodulatory effects of selank in patients with anxiety-asthenic disorders].\" Zh Nevrol Psikhiatr Im S S Korsakova, 2008;108(5):71-5. PMID: 18577961.", "pmid": "18577961" }, { "type": "pubmed", "citation": "Zozulya AA, et al. \"The inhibitory effect of Selank on enkephalin-degrading enzymes as a possible mechanism of its anxiolytic activity.\" Bull Exp Biol Med, 2001;131(4):315-7. PMID: 11550013.", "pmid": "11550013" }, { "type": "pubmed", "citation": "Panikratova YR, et al. \"Functional Connectomic Approach to Studying Selank and Semax Effects.\" Dokl Biol Sci, 2020;490(1):9-11. PMID: 32342318.", "pmid": "32342318" }, { "type": "review", "citation": "Doyno CR, et al. \"Sedative-Hypnotic Agents That Impact Gamma-Aminobutyric Acid Receptors: Focus on Flunitrazepam, Gamma-Hydroxybutyric Acid, Phenibut, and Selank.\" J Clin Pharmacol, 2021;61 Suppl 2:S114-S128. PMID: 34396551.", "pmid": "34396551" }, { "type": "pubmed", "citation": "Volkova A, et al. \"Selank Administration Affects the Expression of Some Genes Involved in GABAergic Neurotransmission.\" Front Pharmacol, 2016;7:31. PMID: 26924987.", "pmid": "26924987" }, { "type": "pubmed", "citation": "Vasil'eva EV, et al. \"[COMPARISON OF PHARMACOLOGICAL EFFECTS OF HEPTAPEPTIDE SELANK AFTER INTRANASAL AND INTRAPERITONEAL ADMINISTRATION TO BALB/c AND C57BL/6 MICE.].\" Eksp Klin Farmakol, 2016;79(9):3-11. PMID: 29787664.", "pmid": "29787664" }, { "type": "pubmed", "citation": "Kasian A, et al. \"Peptide Selank Enhances the Effect of Diazepam in Reducing Anxiety in Unpredictable Chronic Mild Stress Conditions in Rats.\" Behav Neurol, 2017;2017:5091027. PMID: 28280289.", "pmid": "28280289" }, { "type": "pubmed", "citation": "Kolik LG, et al. \"Efficacy of peptide anxiolytic selank during modeling of withdrawal syndrome in rats with stable alcoholic motivation.\" Bull Exp Biol Med, 2014;157(1):52-5. PMID: 24913576.", "pmid": "24913576" }, { "type": "pubmed", "citation": "Konstantinopolsky MA, et al. \"Selank, a Peptide Analog of Tuftsin, Attenuates Aversive Signs of Morphine Withdrawal in Rats.\" Bull Exp Biol Med, 2022;173(6):730-733. PMID: 36322304.", "pmid": "36322304" }, { "type": "pubmed", "citation": "Kolik LG, et al. \"Selank, Peptide Analogue of Tuftsin, Protects Against Ethanol-Induced Memory Impairment by Regulating of BDNF Content in the Hippocampus and Prefrontal Cortex in Rats.\" Bull Exp Biol Med, 2019;167(5):641-644. PMID: 31625062.", "pmid": "31625062" }, { "type": "pubmed", "citation": " \"[Compensatory and antiamnestic effects of heptapeptide Selank in monkeys].\" Zh Evol Biokhim Fiziol, 2008;44(3):284-90. PMID: 18727417.", "pmid": "18727417" }, { "type": "pubmed", "citation": "Zozulya AA, et al. \"Efficacy of novel selective anxiolytic Selank.\" Bull Exp Biol Med, 2008;146:694-695." }, { "type": "other", "citation": "Peptogen. Selank (nasal drops 0.15%), instruction for medical use, Russian registration LP-No(010951)-(RG-RU), approved by the Ministry of Health of the Russian Federation (manufacturer's copy and RLS; read September 30, 2026): adults 18 and over, 2 drops in each nostril 3 times a day for 14 days." } ], "interactionCoverage": "none-found", "related": [ "semax", "cerebrolysin", "pe-22-28" ], "lastReviewed": "2026-09-26", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": "Russia", "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "semaglutide", "name": "Semaglutide", "aliases": [ "Ozempic", "Wegovy", "Rybelsus", "NN9535" ], "tier": "full", "category": "metabolic", "subcategory": "GLP-1 receptor agonist", "class": "Long-acting GLP-1 receptor agonist with backbone modifications for weekly subcutaneous or daily oral administration.", "tagline": "A once-weekly GLP-1 receptor agonist FDA-approved for type 2 diabetes and chronic weight management.", "oneLiner": "A synthetic GLP-1 analog with 94% sequence homology to native human GLP-1, engineered for a ~7-day half-life via fatty acid conjugation.", "sequence": "HAEGTFTSDVSSYLEGQAAKEFIAWLVRGRG (with Aib at position 8 and C18 fatty acid at Lys26)", "molecularFormula": "C187H291N45O59", "molecularWeight": 4113.58, "halfLife": { "value": 7, "unit": "days", "range": "~7 days", "notes": "Albumin binding via fatty acid side chain extends half-life; steady state reached in 4–5 weeks." }, "fdaStatus": "approved", "approvalDetails": "FDA-approved as Ozempic (type 2 diabetes, 2017), Rybelsus (oral type 2 diabetes, 2019) and Wegovy (chronic weight management, 2021), all Novo Nordisk. Drugs@FDA now lists two Wegovy applications: the injection (NDA 215256), which includes Wegovy HD at 7.2 mg/0.75 mL and a Wegovy FlexTouch pen at 9.6 mg/3 mL, and Wegovy tablets (NDA 218316) at 1.5, 4, 9 and 25 mg. Oral semaglutide also appears under NDA 213051 as both Rybelsus and Ozempic tablets.", "mechanism": "Agonist at the GLP-1 receptor. Enhances glucose-dependent insulin secretion, suppresses inappropriate glucagon, slows gastric emptying, and acts centrally to reduce appetite via hypothalamic and area postrema pathways. Weight loss is driven primarily by the central appetite-suppressing effect rather than the peripheral metabolic actions.", "primaryUses": [ "Type 2 diabetes mellitus", "Chronic weight management (BMI ≥30, or ≥27 with comorbidity)", "Cardiovascular risk reduction in T2DM with established CVD (SELECT trial)" ], "typicalDose": { "range": "0.25–2.4", "unit": "mg", "frequency": "weekly", "route": "subcutaneous (Ozempic/Wegovy); oral daily (Rybelsus)", "notes": "Titrated over 16–20 weeks to minimize GI side effects. Wegovy maintenance is 2.4 mg weekly; Ozempic diabetes doses are 0.5–2.0 mg weekly." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Ozempic (semaglutide) Prescribing Information. Novo Nordisk.", "url": "https://www.novo-pi.com/ozempic.pdf" }, { "type": "fda-pi", "citation": "Wegovy (semaglutide) Prescribing Information. Novo Nordisk." }, { "type": "clinical-trial", "citation": "Wilding JPH, et al. \"Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1).\" N Engl J Med, 2021;384:989-1002. PMID: 33567185.", "pmid": "33567185" }, { "type": "clinical-trial", "citation": "Lincoff AM, et al. \"Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT).\" N Engl J Med, 2023;389:2221-2232. PMID: 37952131.", "pmid": "37952131" }, { "type": "pubmed", "citation": "Perkovic V, et al. \"Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes.\" N Engl J Med, 2024;391(2):109-121. PMID: 38785209.", "pmid": "38785209" }, { "type": "pubmed", "citation": "Moore PW, et al. \"GLP-1 Agonists for Weight Loss: Pharmacology and Clinical Implications.\" Adv Ther, 2023;40(3):723-742. PMID: 36566341.", "pmid": "36566341" }, { "type": "pubmed", "citation": "Weghuber D, et al. \"Once-Weekly Semaglutide in Adolescents with Obesity.\" N Engl J Med, 2022;387(24):2245-2257. PMID: 36322838.", "pmid": "36322838" }, { "type": "pubmed", "citation": "Garvey WT, et al. \"Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial.\" Nat Med, 2022;28(10):2083-2091. PMID: 36216945.", "pmid": "36216945" }, { "type": "pubmed", "citation": "Rubino DM, et al. \"Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial.\" JAMA, 2022;327(2):138-150. PMID: 35015037.", "pmid": "35015037" }, { "type": "pubmed", "citation": "Husain M, et al. \"Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes.\" N Engl J Med, 2019;381(9):841-851. PMID: 31185157.", "pmid": "31185157" }, { "type": "pubmed", "citation": "Lau J, et al. \"Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide.\" J Med Chem, 2015;58(18):7370-80. PMID: 26308095.", "pmid": "26308095" }, { "type": "pubmed", "citation": "Knudsen LB, et al. \"The Discovery and Development of Liraglutide and Semaglutide.\" Front Endocrinol (Lausanne), 2019;10:155. PMID: 31031702.", "pmid": "31031702" }, { "type": "pubmed", "citation": "Gabery S, et al. \"Semaglutide lowers body weight in rodents via distributed neural pathways.\" JCI Insight, 2020;5(6). PMID: 32213703.", "pmid": "32213703" }, { "type": "pubmed", "citation": "Blundell J, et al. \"Effects of once-weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity.\" Diabetes Obes Metab, 2017;19(9):1242-1251. PMID: 28266779.", "pmid": "28266779" } ], "interactionCoverage": "full", "related": [ "tirzepatide", "retatrutide", "liraglutide" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-18", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "monitoring": "markers of semaglutide and tirzepatide, in and out of competition" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "monitoring": "GLP-1 receptor agonists: semaglutide and tirzepatide, in and out of competition" } ], "moleculeClass": "peptide", "statusVerified": { "date": "2026-09-30", "source": "US FDA, Drugs@FDA (openFDA): NDA 215256 (Wegovy injection, incl. WEGOVY HD 7.2 mg/0.75 mL and WEGOVY FLEXTOUCH 9.6 mg/3 mL), NDA 218316 (Wegovy tablets 1.5/4/9/25 mg, latest supplement approved 2026-06-18), NDA 213051 (Rybelsus and Ozempic tablets); all prescription." } }, { "id": "semax", "name": "Semax", "aliases": [ "ACTH(4-7)PGP", "methionyl-glutamyl-histidyl-phenylalanyl-prolyl-glycyl-proline" ], "tier": "full", "category": "cognitive", "subcategory": "ACTH-derived neuropeptide", "class": "A synthetic heptapeptide derived from ACTH(4-10), developed in Russia as a stabilized fragment lacking the hormonal activity of ACTH.", "tagline": "A synthetic ACTH-derived heptapeptide approved in Russia for stroke rehabilitation and optic nerve disorders, with documented BDNF upregulation and broad nootropic activity.", "oneLiner": "A 7-amino-acid stabilized fragment of ACTH(4-10) developed at the Institute of Molecular Genetics (Moscow) in the 1980s, with the C-terminal PGP extension conferring protease resistance and retaining the neurotrophic/nootropic activity without the corticotropic effect.", "sequence": "Met-Glu-His-Phe-Pro-Gly-Pro", "molecularFormula": "C37H51N9O10S", "molecularWeight": 813.93, "halfLife": { "value": null, "unit": null, "range": "not measured in humans", "notes": "In rats, intranasal semax reached the brain within 2 minutes and was rapidly broken down, mostly to Pro-Gly-Pro (Shevchenko 2006). No human half-life appears in the abstracts we hold; the '~30 minutes' given here before had no source." }, "fdaStatus": "not-approved-us", "approvalDetails": "Approved as a medicine in Russia, where it is used as nasal drops, including in stroke and optic-nerve disease. Not approved by the FDA or in the EU, UK, Canada or Australia.", "mechanism": "In rats, a single dose raised hippocampal BDNF protein 1.4-fold and exon III BDNF mRNA threefold, with more trkB activation, and intranasal doses raised basal-forebrain BDNF within three hours; it binds specific sites there. It increased striatal serotonin turnover and strongly amplified amphetamine's dopamine and locomotor effects. In rat stroke models it shifts immune-response gene expression. How these findings translate to people is not established.", "primaryUses": [ "Stroke rehabilitation (Russian approval)", "Optic neuropathy (Russian approval)", "Cognitive enhancement during acute stress", "Anxiety and mood research" ], "typicalDose": { "range": "250–600", "unit": "mcg", "frequency": "2–3 times daily", "route": "intranasal", "notes": "Russian clinical dosing: 0.1% solution, 2–3 drops per nostril, 2–3 times daily." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "Dolotov OV, et al. \"Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal forebrain.\" J Neurochem, 2006;97 Suppl 1:82-6. PMID: 16635254.", "pmid": "16635254" }, { "type": "pubmed", "citation": "Dolotov OV, et al. \"Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus.\" Brain Res, 2006;1117(1):54-60. PMID: 16996037.", "pmid": "16996037" }, { "type": "pubmed", "citation": "Eremin KO, et al. \"Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents.\" Neurochem Res, 2005;30(12):1493-500. PMID: 16362768.", "pmid": "16362768" }, { "type": "pubmed", "citation": "Medvedeva EV, et al. \"Semax, an analog of ACTH((4-7)), regulates expression of immune response genes during ischemic brain injury in rats.\" Mol Genet Genomics, 2017;292(3):635-653. PMID: 28255762.", "pmid": "28255762" }, { "type": "pubmed", "citation": "Gusev EI, et al. \"[The efficacy of semax in the tretament of patients at different stages of ischemic stroke].\" Zh Nevrol Psikhiatr Im S S Korsakova, 2018;118(3. Vyp. 2):61-68. PMID: 29798983.", "pmid": "29798983" }, { "type": "pubmed", "citation": "Gusev EI, et al. \"[Effectiveness of semax in acute period of hemispheric ischemic stroke (a clinical and electrophysiological study)].\" Zh Nevrol Psikhiatr Im S S Korsakova, 1997;97(6):26-34. PMID: 11517472.", "pmid": "11517472" }, { "type": "pubmed", "citation": "Polunin GS, et al. \"[Evaluation of therapeutic effect of new Russian drug semax in optic nerve disease].\" Vestn Oftalmol, 2000;116(1):15-8. PMID: 10741256.", "pmid": "10741256" }, { "type": "pubmed", "citation": "Lebedeva IS, et al. \"Effects of Semax on the Default Mode Network of the Brain.\" Bull Exp Biol Med, 2018;165(5):653-656. PMID: 30225715.", "pmid": "30225715" }, { "type": "pubmed", "citation": "Ivanikov IO, et al. \"Therapy of peptic ulcer with semax peptide.\" Bull Exp Biol Med, 2002;134(1):73-4. PMID: 12459874.", "pmid": "12459874" }, { "type": "pubmed", "citation": "Serdiuk AV, et al. \"[The study of chronic partial denervation and quality of life in patients with motor neuron disease treated with semax].\" Zh Nevrol Psikhiatr Im S S Korsakova, 2007;107(4):29-39. PMID: 18379501.", "pmid": "18379501" }, { "type": "pubmed", "citation": "Tomasello MF, et al. \"Semax, a Copper Chelator Peptide, Decreases the Cu(II)-Catalyzed ROS Production and Cytotoxicity of aβ by Metal Ion Stripping and Redox Silencing.\" Bioinorg Chem Appl, 2025;2025:4226220. PMID: 40496623.", "pmid": "40496623" }, { "type": "pubmed", "citation": "Myasoedov NF, et al. \"Heptapeptide Semax and its neurotropic actions.\" Zh Vyssh Nerv Deiat Im I P Pavlova, 1999;49:646-652." }, { "type": "pubmed", "citation": "Gusev EI, et al. \"Neuroprotective effects of Semax in acute ischemic stroke.\" Zh Nevrol Psikhiatr Im S S Korsakova, 2005;105:41-46." } ], "interactionCoverage": "studied", "related": [ "selank", "cerebrolysin", "noopept", "pe-22-28" ], "lastReviewed": "2026-09-26", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": "Russia", "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "sermorelin", "name": "Sermorelin", "aliases": [ "Geref", "GHRH(1-29)", "GRF(1-29)", "Sermorelin acetate" ], "tier": "full", "category": "growth-hormone", "subcategory": "GHRH analog", "class": "A 29-amino-acid synthetic fragment of native human GHRH — the shortest sequence retaining full biological activity.", "tagline": "GHRH's first 29 amino acids, sold in the US as Geref (approved 1990 and 1997) to test and treat childhood growth hormone deficiency until it was discontinued, not for safety reasons.", "oneLiner": "A 29-amino-acid peptide corresponding to the biologically active N-terminal fragment of growth hormone-releasing hormone, formerly marketed as Geref for pediatric GH deficiency and as a diagnostic agent.", "sequence": "H-Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-NH2", "molecularFormula": "C149H246N44O42S", "molecularWeight": 3357.88, "halfLife": { "value": null, "unit": null, "range": "not established in our sources", "notes": "No pharmacokinetic study is in our evidence set, and the Geref labels were withdrawn with the product. Growth hormone peaked 15 to 45 minutes after a dose in small human studies." }, "fdaStatus": "discontinued", "approvalDetails": "FDA-approved as Geref (EMD Serono): a 0.05 mg diagnostic ampoule on December 28, 1990 (NDA 19-863) and 0.5 and 1.0 mg vials on September 26, 1997 (NDA 20-443), for children with idiopathic growth hormone deficiency. Both were discontinued; on March 4, 2013 FDA determined Geref was not withdrawn from sale for reasons of safety or effectiveness.", "mechanism": "GHRH receptor agonist: the 29-amino-acid active fragment of GHRH, which stimulates growth hormone secretion from the anterior pituitary. Used as a 1 µg/kg intravenous test of pituitary reserve (a normal response cannot exclude hypothalamic deficiency) and, as Geref, as a nightly treatment for children with idiopathic growth hormone deficiency.", "primaryUses": [ "Pediatric growth hormone deficiency (historical FDA indication)", "GH-axis diagnostic testing (historical)", "Adult GH-optimization protocols (current compounded/off-label use)" ], "typicalDose": { "range": "200–500", "unit": "mcg", "frequency": "once or twice daily", "route": "subcutaneous", "notes": "Community and compounding figures for adults, with no trial behind them. The pediatric Geref dose in the 1999 review was 30 µg/kg once nightly under the skin; the diagnostic dose was 1 µg/kg intravenously." }, "evidenceLevel": "medium", "sources": [ { "type": "fda-pi", "citation": "Geref (sermorelin acetate) Prescribing Information. EMD Serono. (Discontinued.)" }, { "type": "other", "citation": "Food and Drug Administration. Determination that GEREF (sermorelin acetate) injection was not withdrawn from sale for reasons of safety or effectiveness. Federal Register 78:14096, March 4, 2013 (Docket FDA-2012-P-1071)." }, { "type": "review", "citation": "Prakash A, et al. \"Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency.\" BioDrugs, 1999;12(2):139-57. PMID: 18031173.", "pmid": "18031173" }, { "type": "pubmed", "citation": "Bueno G, et al. \"Priming with GHRH (1-29) NH2: an aid in differential diagnosis between hypothalamic and pituitary deficiencies.\" J Pediatr Endocrinol, 1994;7(4):309-16. PMID: 7735368.", "pmid": "7735368" }, { "type": "pubmed", "citation": "Alvarez XA, et al. \"Effects of GRF (1-29) NH2 on short-term memory: neuroendocrine and neuropsychological assessment in healthy young subjects.\" Methods Find Exp Clin Pharmacol, 1990;12(7):493-9. PMID: 2087150.", "pmid": "2087150" }, { "type": "pubmed", "citation": "Borkenstein M. \"The effects of intranasal insufflation of growth hormone releasing factor analogue GRF 1-29 NH2 on growth hormone secretion in children with short stature.\" Acta Endocrinol Suppl (Copenh), 1986;279:135-8. PMID: 2877535.", "pmid": "2877535" }, { "type": "pubmed", "citation": "Jordan V, et al. \"Lack of effect of muscarinic cholinergic blockade on the GH responses to GRF 1-29 and TRH in acromegalic subjects.\" Clin Endocrinol (Oxf), 1986;24(4):415-20. PMID: 2874906.", "pmid": "2874906" }, { "type": "pubmed", "citation": "Mariette B, et al. \"Interactions of GRF(1-29)NH2 with plasma proteins and their effects on the release of the peptide from a PLAGA matrix.\" J Control Release, 2005;106(3):253-62. PMID: 15987661.", "pmid": "15987661" }, { "type": "review", "citation": "Walker RF. \"Sermorelin: a better approach to management of adult-onset growth hormone insufficiency?.\" Clin Interv Aging, 2006;1(4):307-8. PMID: 18046908.", "pmid": "18046908" } ], "interactionCoverage": "partial", "related": [ "cjc-1295", "mod-grf-1-29", "ipamorelin", "tesamorelin" ], "lastReviewed": "2026-09-26", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.2.4", "named": true, "wording": "sermorelin", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.2.4", "named": true, "wording": "sermorelin", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "setmelanotide", "name": "Setmelanotide", "aliases": [ "Imcivree", "RM-493", "BIM-22493" ], "tier": "mid", "category": "metabolic", "subcategory": "MC4R agonist", "class": "A synthetic cyclic octapeptide melanocortin-4 receptor (MC4R) agonist for treatment of obesity caused by rare genetic deficiencies in the leptin-melanocortin pathway.", "tagline": "An MC4 receptor agonist peptide sold as Imcivree, approved in the US for obesity due to Bardet-Biedl syndrome or POMC, PCSK1 or LEPR deficiency (from age 2) and acquired hypothalamic obesity (from age 4). In hypothalamic obesity, BMI fell 16.5% against a 3.3% rise on placebo over 52 weeks.", "oneLiner": "A melanocortin-4 (MC4) receptor agonist peptide sold as Imcivree (Rhythm Pharmaceuticals). Its US label covers obesity due to Bardet-Biedl syndrome or POMC, PCSK1 or LEPR deficiency from age 2, and acquired hypothalamic obesity from age 4.", "sequence": "Ac-Arg-cyclo(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2", "molecularFormula": "C49H68N18O9S2", "molecularWeight": 1117.31, "halfLife": { "value": 11, "unit": "hours", "range": "about 11 hours (effective elimination)", "notes": "Given once daily by subcutaneous injection.", "source": { "type": "label", "ref": "Imcivree prescribing information, section 12.3 (DailyMed version 14, effective April 1, 2026; read September 30, 2026)" } }, "fdaStatus": "approved", "approvalDetails": "Imcivree (NDA 213793), prescription. Current US label (DailyMed version 14, effective April 1, 2026): acquired hypothalamic obesity from age 4; Bardet-Biedl syndrome and POMC, PCSK1 or LEPR deficiency from age 2.", "mechanism": "Selective MC4R agonist (EC50 ~0.27 nM). In the leptin-melanocortin pathway, leptin activates POMC neurons in the arcuate nucleus of the hypothalamus; POMC is cleaved by PCSK1 into α-MSH, which activates MC4R on downstream paraventricular neurons to reduce hunger and increase energy expenditure. Loss-of-function in POMC, PCSK1, or LEPR disrupts this signal; BBS causes primary ciliary dysfunction impairing MC4R trafficking. Setmelanotide bypasses the upstream defect by directly agonizing MC4R, restoring satiety signaling and producing clinically meaningful weight loss. Note: not effective for common polygenic obesity, which is why setmelanotide labeling requires confirmed genetic diagnosis.", "primaryUses": [ "Obesity due to POMC, PCSK1 or LEPR deficiency (FDA-approved, age 2 and older)", "Obesity in Bardet-Biedl syndrome (FDA-approved, age 2 and older)", "Acquired hypothalamic obesity (FDA-approved, age 4 and older)" ], "typicalDose": { "range": "0.5–3", "unit": "mg", "frequency": "once daily", "route": "subcutaneous", "notes": "Label starting doses 0.5 to 2 mg by indication and age; the trials used up to 3 mg." }, "evidenceLevel": "high", "sources": [ { "type": "fda", "citation": "FDA. Drugs@FDA (openFDA): IMCIVREE (setmelanotide), NDA 213793, prescription. Read September 30, 2026." }, { "type": "fda", "citation": "Rhythm Pharmaceuticals. IMCIVREE (setmelanotide) injection, US prescribing information: sections 1, 2 and 12.3. DailyMed version 14, effective April 1, 2026. Read September 30, 2026." }, { "type": "pubmed", "citation": "Miller JL, et al. \"Setmelanotide for the Treatment of Acquired Hypothalamic Obesity.\" N Engl J Med, 2026;395(2):138-150. PMID: 42418774.", "pmid": "42418774" }, { "type": "pubmed", "citation": "Roth CL, et al. \"Setmelanotide for the treatment of acquired hypothalamic obesity: a phase 2, open-label, multicentre trial.\" Lancet Diabetes Endocrinol, 2024;12(6):380-389. PMID: 38697184.", "pmid": "38697184" }, { "type": "pubmed", "citation": "Clément K, et al. \"Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials.\" Lancet Diabetes Endocrinol, 2020;8(12):960-970. PMID: 33137293.", "pmid": "33137293" }, { "type": "pubmed", "citation": "Haqq AM, et al. \"Efficacy and safety of setmelanotide, a melanocortin-4 receptor agonist, in patients with Bardet-Biedl syndrome and Alström syndrome: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial with an open-label period.\" Lancet Diabetes Endocrinol, 2022;10(12):859-868. PMID: 36356613.", "pmid": "36356613" }, { "type": "pubmed", "citation": "Argente J, et al. \"Setmelanotide in patients aged 2-5 years with rare MC4R pathway-associated obesity (VENTURE): a 1 year, open-label, multicenter, phase 3 trial.\" Lancet Diabetes Endocrinol, 2025;13(1):29-37. PMID: 39549719.", "pmid": "39549719" } ], "interactionCoverage": "partial", "related": [ "pt-141", "melanotan-ii", "afamelanotide" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "shlp1", "name": "SHLP1", "aliases": [ "Small Humanin-Like Peptide 1", "SHLP-1" ], "tier": "stub", "category": "longevity", "subcategory": "Mitochondrial-derived peptide", "class": "SHLP1 is the first of the six small humanin-like peptides encoded within mitochondrial DNA, extending the mitochondrial-derived peptide family alongside humanin and MOTS-c.", "tagline": "The first small humanin-like peptide — a mitochondrial-derived signaling molecule with chaperone-like cytoprotective activity.", "oneLiner": "A mitochondrial-derived peptide encoded within the MT-RNR2 gene that exhibits chaperone-like cytoprotective activity, protecting cells from oxidative stress and apoptosis.", "sequence": "MCHWAGGASNTGDARGC (putative, 17 aa)", "molecularFormula": "Estimated ~1.7 kDa", "molecularWeight": 1700, "halfLife": { "value": null, "unit": null, "range": "Undetermined", "notes": "Pharmacokinetic data not established." }, "fdaStatus": "research-only", "approvalDetails": "Not approved. Early-stage research peptide in the emerging MDP field.", "mechanism": "Encoded within the 16S rRNA gene (MT-RNR2) of mitochondrial DNA. Demonstrates chaperone-like activity, stabilizing protein folding under stress conditions.", "primaryUses": [ "Research: mitochondrial-derived peptide biology", "Cytoprotection research", "Aging and neurodegeneration research" ], "typicalDose": { "range": "N/A", "unit": "N/A", "frequency": "N/A", "route": "research only", "notes": "No established dosing." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Cobb LJ, et al. \"Naturally occurring mitochondrial-derived peptides are age-dependent regulators of apoptosis, insulin sensitivity, and inflammatory markers.\" Aging. 2016;8(4):796-809. PMID: 27070352.", "pmid": "27070352" } ], "interactionCoverage": "unreviewed", "related": [ "shlp2", "shlp3", "shlp6", "humanin", "mots-c" ], "lastReviewed": "2026-04-21", "publishedAt": "2026-04-21", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "shlp2", "name": "SHLP2", "aliases": [ "Small humanin-like peptide 2", "MT-RNR2-derived SHLP2" ], "tier": "stub", "category": "longevity", "subcategory": "Small humanin-like peptide (mitochondrial-derived)", "class": "A 26-amino-acid mitochondrial-derived peptide encoded by an alternate reading frame within the 16S ribosomal RNA gene of mitochondrial DNA; the most-studied of the six small humanin-like peptides (SHLP1–SHLP6).", "tagline": "A 26-aa mitochondrial-derived peptide, the most-studied of the SHLP1–SHLP6 family (Cohen lab, USC). Preclinical data report insulin-sensitizing, antiapoptotic, and metabolic-protective effects; lower plasma levels in humans correlate with age and with type 2 diabetes. Research-only; no human clinical trials.", "oneLiner": "A 26-amino-acid mitochondrial-derived peptide (MDP) encoded by a small alternate open reading frame within the 16S rRNA region of mitochondrial DNA, identified and characterized by Pinchas Cohen's group at USC along with five related peptides (SHLP1, SHLP3, SHLP4, SHLP5, SHLP6). The most-studied member of the family. Reported in preclinical studies to enhance insulin sensitivity, protect against β-cell apoptosis in diabetes models, and improve metabolic phenotype in aged mice. Human plasma levels decline with age and are reduced in type 2 diabetes cohorts, supporting a proposed role as an endogenous longevity-associated signal. Research-only; no clinical trials; not available as a registered medicine.", "sequence": "26 amino acids (Pro-Gly-Val-Lys-Phe-Leu-Lys-Ala-Thr-Gly-Gln-Pro-Pro-Pro-Pro-Leu-Pro-Trp-Ala-Phe-Lys-Ala-His-Pro-Ser-Leu — as reported by Cohen group)", "molecularFormula": null, "molecularWeight": 2853.37, "halfLife": { "value": null, "unit": null, "range": "Not formally characterized in humans", "notes": "Endogenous plasma concentrations are low (pg/mL range) and measurable by targeted mass spectrometry. No formal pharmacokinetics of exogenous administration in humans." }, "fdaStatus": "research-only", "approvalDetails": "Not FDA-approved. Not in any registered human clinical trial. Available only as a synthesized research peptide from peptide-synthesis vendors; any human use would be unapproved and unsupported.", "mechanism": "Proposed to be secreted from mitochondria and act in autocrine/paracrine fashion. Reported to enhance insulin signaling (PI3K/Akt), protect pancreatic β-cells from apoptosis, reduce oxidative stress, and modulate adipogenesis. Receptor target is not definitively identified but has been proposed to include the CNTFR-WSX-1-gp130 receptor complex used by humanin. Represents one of the clearest examples of a peptide encoded by the mitochondrial genome in an alternate reading frame with autocrine/endocrine bioactivity.", "primaryUses": [ "Metabolic aging research (preclinical)", "Type 2 diabetes mechanism research (preclinical)", "Mitochondrial-derived peptide biology (aging biomarker research)" ], "typicalDose": { "range": "Not established for human use", "unit": null, "frequency": null, "route": null, "notes": "⚠ No human dosing established. Preclinical rodent studies have used intraperitoneal administration of 1–4 mg/kg. Any human use would be unregulated and unsupported by clinical safety or efficacy data." }, "evidenceLevel": "medium", "sources": [ { "type": "pubmed", "citation": "Cobb LJ, et al. \"Naturally occurring mitochondrial-derived peptides are age-dependent regulators of apoptosis, insulin sensitivity, and inflammatory markers.\" Aging (Albany NY), 2016;8:796-809 (SHLP1–SHLP6 discovery and characterization). PMID: 27070352.", "pmid": "27070352" }, { "type": "pubmed", "citation": "Yen K, et al. \"The mitochondrial derived peptide humanin is a regulator of lifespan and healthspan.\" Aging (Albany NY), 2020;12:11185-11199 (mitochondrial-derived peptide family review). PMID: 32575074.", "pmid": "32575074" }, { "type": "pubmed", "citation": "Mehta HH, et al. \"Mitochondrial-derived peptides as biomarkers of aging and age-related diseases.\" Aging Cell, 2022;21:e13641." } ], "interactionCoverage": "unreviewed", "related": [ "humanin", "mots-c", "shlp6" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "shlp3", "name": "SHLP3", "aliases": [ "Small humanin-like peptide 3", "MT-RNR2-derived SHLP3" ], "tier": "stub", "category": "longevity", "subcategory": "Small humanin-like peptide (mitochondrial-derived)", "class": "A mitochondrial-derived peptide encoded by an alternate open reading frame within the 16S rRNA region of mitochondrial DNA, one of the six small humanin-like peptides (SHLP1–SHLP6).", "tagline": "One of the six small humanin-like peptides (Cohen lab); preclinical reports suggest roles in adipogenesis and metabolic regulation. Less well-characterized than SHLP2 or humanin. Research-only.", "oneLiner": "A mitochondrial-derived peptide in the SHLP1–SHLP6 family, identified by Cohen's group alongside the other SHLPs and reported preclinically to modulate adipogenesis and glucose metabolism. Less extensively characterized than SHLP2. Research-only; no human clinical data.", "sequence": "Mitochondrial 16S rRNA alternate reading frame; sequence reported by Cohen group in SHLP family characterization", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": null, "range": "Not formally characterized", "notes": "No pharmacokinetic data from exogenous administration in humans." }, "fdaStatus": "research-only", "approvalDetails": "Not FDA-approved. No registered clinical trials. Research-only.", "mechanism": "Proposed to modulate adipocyte differentiation and glucose handling via mitochondrial-derived peptide signaling. Receptor target not definitively characterized. Mechanistic understanding is less developed than for SHLP2 or humanin.", "primaryUses": [ "Adipogenesis research (preclinical)", "Mitochondrial-derived peptide biology (aging research)" ], "typicalDose": { "range": "Not established for human use", "unit": null, "frequency": null, "route": null, "notes": "⚠ No human dosing established. Any human use would be unregulated and unsupported." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Cobb LJ, et al. \"Naturally occurring mitochondrial-derived peptides are age-dependent regulators of apoptosis, insulin sensitivity, and inflammatory markers.\" Aging (Albany NY), 2016;8:796-809. PMID: 27070352.", "pmid": "27070352" }, { "type": "pubmed", "citation": "Yen K, et al. \"The mitochondrial derived peptide humanin is a regulator of lifespan and healthspan.\" Aging (Albany NY), 2020;12:11185-11199. PMID: 32575074.", "pmid": "32575074" } ], "interactionCoverage": "unreviewed", "related": [ "humanin", "shlp2", "shlp6" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "shlp4", "name": "SHLP4", "aliases": [ "Small Humanin-Like Peptide 4", "SHLP-4" ], "tier": "stub", "category": "longevity", "subcategory": "Mitochondrial-derived peptide", "class": "SHLP4 is a mitochondrial-derived peptide notable for its association with cellular proliferation, distinguishing it from the anti-apoptotic SHLPs 2, 3, and 6.", "tagline": "A mitochondrial-derived peptide linked to cellular proliferation and insulin sensitivity.", "oneLiner": "A mitochondrial-derived peptide encoded within MT-RNR2 that promotes cellular proliferation and may influence insulin sensitivity.", "sequence": "Putative short peptide (~20-30 aa)", "molecularFormula": "Estimated ~2-3 kDa", "molecularWeight": 2500, "halfLife": { "value": null, "unit": null, "range": "Undetermined", "notes": "No PK data available." }, "fdaStatus": "research-only", "approvalDetails": "Not approved. Early-stage research.", "mechanism": "Encoded in MT-RNR2 of mitochondrial DNA. Unlike anti-apoptotic SHLPs 2, 3, and 6, SHLP4 appears to promote cell proliferation. May influence glucose metabolism.", "primaryUses": [ "Research: SHLP family characterization", "Cell proliferation and metabolism research" ], "typicalDose": { "range": "N/A", "unit": "N/A", "frequency": "N/A", "route": "research only", "notes": "Very early-stage." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Cobb LJ, et al. \"Naturally occurring mitochondrial-derived peptides are age-dependent regulators of apoptosis, insulin sensitivity, and inflammatory markers.\" Aging. 2016;8(4):796-809. PMID: 27070352.", "pmid": "27070352" } ], "interactionCoverage": "unreviewed", "related": [ "shlp1", "shlp2", "shlp3", "shlp5", "shlp6", "humanin", "mots-c" ], "lastReviewed": "2026-04-21", "publishedAt": "2026-04-21", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "shlp5", "name": "SHLP5", "aliases": [ "Small Humanin-Like Peptide 5", "SHLP-5" ], "tier": "stub", "category": "longevity", "subcategory": "Mitochondrial-derived peptide", "class": "SHLP5 is a mitochondrial-derived peptide with preliminary associations with mitochondrial metabolism and cellular stress responses.", "tagline": "A mitochondrial-derived peptide with emerging roles in metabolic regulation and cellular stress protection.", "oneLiner": "A mitochondrial-derived peptide encoded within MT-RNR2 with preliminary evidence of roles in mitochondrial metabolism and ROS management.", "sequence": "Putative short peptide (~20-30 aa)", "molecularFormula": "Estimated ~2-3 kDa", "molecularWeight": 2500, "halfLife": { "value": null, "unit": null, "range": "Undetermined", "notes": "No PK data." }, "fdaStatus": "research-only", "approvalDetails": "Not approved. Early-stage research.", "mechanism": "Encoded in MT-RNR2 of mitochondrial DNA. Circulating levels decline with age. Preliminary data suggest involvement in mitochondrial ROS management.", "primaryUses": [ "Research: MDP family characterization", "Aging and metabolic research" ], "typicalDose": { "range": "N/A", "unit": "N/A", "frequency": "N/A", "route": "research only", "notes": "Very early-stage." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Cobb LJ, et al. \"Naturally occurring mitochondrial-derived peptides are age-dependent regulators of apoptosis, insulin sensitivity, and inflammatory markers.\" Aging. 2016;8(4):796-809. PMID: 27070352.", "pmid": "27070352" } ], "interactionCoverage": "none-found", "related": [ "shlp1", "shlp2", "shlp3", "shlp4", "shlp6", "humanin", "mots-c" ], "lastReviewed": "2026-04-21", "publishedAt": "2026-04-21", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "shlp6", "name": "SHLP6", "aliases": [ "Small humanin-like peptide 6", "MT-RNR2-derived SHLP6" ], "tier": "stub", "category": "longevity", "subcategory": "Small humanin-like peptide (mitochondrial-derived)", "class": "A mitochondrial-derived peptide in the SHLP1–SHLP6 family, reported in preclinical studies to have pro-apoptotic effects in contrast to the antiapoptotic humanin and SHLP2.", "tagline": "A SHLP-family member with a notably distinct preclinical profile: where humanin and SHLP2 are antiapoptotic, SHLP6 has been reported as pro-apoptotic, suggesting the mitochondrial-derived peptide family includes members with opposing regulatory roles. Research-only.", "oneLiner": "A mitochondrial-derived peptide in the SHLP1–SHLP6 family. Notably distinct from humanin, SHLP2, and MOTS-c in its reported pro-apoptotic effect in multiple cell-culture models, suggesting that the broader mitochondrial-derived peptide family includes members with opposing regulatory roles rather than all acting as uniformly cytoprotective. Research-only; no clinical development.", "sequence": "Mitochondrial 16S rRNA alternate reading frame; sequence reported by Cohen group", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": null, "range": "Not formally characterized", "notes": "No pharmacokinetic data from exogenous administration." }, "fdaStatus": "research-only", "approvalDetails": "Not FDA-approved. Research-only. No registered clinical trials.", "mechanism": "Proposed pro-apoptotic activity — contrasting with humanin, SHLP2, and MOTS-c. The biological significance of this is debated; one hypothesis is that SHLP6 represents an \"off-switch\" balancing the prosurvival effects of other mitochondrial-derived peptides. Molecular target and receptor engagement are not established.", "primaryUses": [ "Mitochondrial-derived peptide biology research (preclinical)", "Apoptosis-regulation research (cell culture)" ], "typicalDose": { "range": "Not established for human use", "unit": null, "frequency": null, "route": null, "notes": "⚠ No human dosing established. Any human use would be unregulated and unsupported." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Cobb LJ, et al. \"Naturally occurring mitochondrial-derived peptides are age-dependent regulators of apoptosis, insulin sensitivity, and inflammatory markers.\" Aging (Albany NY), 2016;8:796-809. PMID: 27070352.", "pmid": "27070352" }, { "type": "pubmed", "citation": "Mehta HH, et al. \"Mitochondrial-derived peptides as biomarkers of aging and age-related diseases.\" Aging Cell, 2022;21:e13641." } ], "interactionCoverage": "unreviewed", "related": [ "humanin", "shlp2", "shlp3" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "snap-8", "name": "SNAP-8", "aliases": [ "Acetyl Octapeptide-3", "Acetyl glutamyl heptapeptide-1" ], "tier": "stub", "category": "cosmetic", "subcategory": "topical cosmetic peptide", "class": "A synthetic octapeptide marketed as a next-generation Argireline analog with extended activity.", "tagline": "An octapeptide cosmetic ingredient extending the Argireline concept — same SNAP-25 competitive mechanism with two additional residues and claims of enhanced activity.", "oneLiner": "An elongated version of Argireline (acetyl octapeptide-3) marketed by Lipotec as a second-generation SNAP-25 mimic for topical expression-line reduction.", "sequence": "Ac-Glu-Glu-Met-Gln-Arg-Arg-Ala-Asp-NH2", "molecularFormula": "C41H70N14O15S", "molecularWeight": 1075.17, "halfLife": { "value": null, "unit": null, "range": "topical only", "notes": "Systemic absorption minimal." }, "fdaStatus": "research-only", "approvalDetails": "Cosmetic ingredient; not a drug.", "mechanism": "Same mechanism as Argireline — competes with SNAP-25 at the SNARE complex, reducing acetylcholine release at the neuromuscular junction. Manufacturer studies claim enhanced potency vs Argireline at equivalent concentrations, but independent replication is limited.", "primaryUses": [ "Topical anti-aging cosmetic formulations" ], "typicalDose": { "range": "5–10", "unit": "% (topical formulation)", "frequency": "daily topical application", "route": "topical", "notes": "Cosmetic concentrations." }, "evidenceLevel": "low", "sources": [ { "type": "manufacturer", "citation": "Lipotec. \"SNAP-8 technical data sheet and cosmetic ingredient profile.\"" } ], "interactionCoverage": "unreviewed", "related": [ "argireline", "matrixyl", "ghk-cu" ], "lastReviewed": "2026-04-18", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." } ], "moleculeClass": "peptide" }, { "id": "somapacitan", "name": "Somapacitan", "aliases": [ "Sogroya", "NN8640", "somapacitan-beco" ], "tier": "stub", "category": "growth-hormone", "subcategory": "once-weekly albumin-binding growth hormone", "class": "A long-acting recombinant human growth hormone derivative in which a fatty-acid-based albumin-binding side chain is attached at position L101C, producing reversible albumin binding and a half-life suitable for once-weekly subcutaneous dosing.", "tagline": "Novo Nordisk's once-weekly growth hormone (Sogroya) — FDA-approved in 2020 for adult GH deficiency and in 2023 for pediatric GH deficiency in children aged 2.5+ years.", "oneLiner": "A once-weekly recombinant human growth hormone derivative engineered with a fatty-acid-based albumin-binding side chain that extends plasma half-life to approximately 2–3 days, allowing weekly subcutaneous administration. FDA-approved as Sogroya for adult growth hormone deficiency in August 2020 and extended in April 2023 to pediatric GH deficiency in children aged 2.5 years and older — the second weekly GH formulation to reach both adult and pediatric indications in the US.", "sequence": "Recombinant hGH backbone with single amino acid substitution (L101C) conjugated to a fatty acid albumin binder", "molecularFormula": null, "molecularWeight": 23305, "halfLife": { "value": 60, "unit": "hours", "range": "~2–3 days", "notes": "Weekly dosing with steady-state reached after approximately 5 doses." }, "fdaStatus": "approved", "approvalDetails": "FDA-approved August 2020 as Sogroya (Novo Nordisk) for replacement of endogenous growth hormone in adults with GHD. Extended April 2023 to pediatric patients aged 2.5 years and older with GH deficiency. Also approved by EMA, Health Canada, Japanese PMDA, and other regulators.", "mechanism": "Binds the GH receptor with affinity comparable to native somatropin, triggering JAK2/STAT5 signaling and downstream IGF-1 production. The L101C albumin-binding side chain reversibly binds circulating albumin (>99% bound), which shields the molecule from rapid renal and receptor-mediated clearance and produces the extended weekly PK profile. Unbound fraction engages the GH receptor and dissociates from albumin to replenish the active pool as it is cleared.", "primaryUses": [ "Adult growth hormone deficiency", "Pediatric growth hormone deficiency (age 2.5+)" ], "typicalDose": { "range": "0.04–0.16", "unit": "mg/kg/week", "frequency": "once weekly", "route": "subcutaneous", "notes": "Adult GHD: 1.5 mg weekly starting, titrated to IGF-1 target (typically 2–8 mg/week). Pediatric GHD: 0.16 mg/kg/week weight-based dosing." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Sogroya (somapacitan-beco) Prescribing Information. Novo Nordisk." }, { "type": "pubmed", "citation": "Johannsson G, et al. \"Safety and convenience of once-weekly somapacitan in adult GH deficiency: a 26-week randomized, controlled trial.\" Eur J Endocrinol, 2018;178:491-499. PMID: 29500310.", "pmid": "29500310" }, { "type": "clinical-trial", "citation": "Miller BS, et al. \"Weekly Somapacitan is Effective and Well Tolerated in Children With GH Deficiency: The Randomized Phase 3 REAL4 Trial.\" J Clin Endocrinol Metab, 2022;107(12):3378-3388. PMID: 36062966.", "pmid": "36062966" } ], "interactionCoverage": "label", "related": [ "somatropin", "lonapegsomatropin", "somatrogon", "sermorelin" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.2.3", "named": true, "wording": "somapacitan", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "A long-acting growth hormone analogue." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.2.3", "named": true, "wording": "somapacitan", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "A long-acting growth hormone analogue." } ], "moleculeClass": "protein", "moleculeClassBasis": "growth hormone derivative" }, { "id": "somatostatin", "name": "Somatostatin", "aliases": [ "SRIF", "Somatotropin release-inhibiting factor", "SST", "SST-14", "SST-28", "GHIH" ], "tier": "mid", "category": "growth-hormone", "subcategory": "Endogenous inhibitory peptide", "class": "Somatostatin is the endogenous cyclic peptide hormone that inhibits growth hormone, insulin, glucagon, and gastrin secretion. It is the natural counterpart to the GHRH/ghrelin axis and the parent molecule for synthetic analogs octreotide, lanreotide, and pasireotide already in the encyclopedia.", "tagline": "The body's hormone off-switch, given by infusion for bleeding varices in Spain and elsewhere; never approved in the US, unlike its analogues.", "oneLiner": "A 14- or 28-amino-acid inhibitory hormone acting on five receptor subtypes; octreotide and lanreotide are its longer-lasting analogues.", "sequence": "AGCKNFFWKTFTSC (SST-14, disulfide bond Cys3-Cys14)", "molecularFormula": "C76H104N18O19S2", "molecularWeight": 1637.88, "halfLife": { "value": null, "unit": null, "range": "a few minutes in plasma, which is why it is given by continuous infusion", "source": { "type": "pmid", "pmid": "19041716", "cite": "Cervin C, et al. \"A combined in vitro and in vivo study on the interactions between somatostatin and lipid-based liquid crystalline drug carriers and bilayers.\" Eur J Pharm Sci, 2009;36(4-5):377-85. PMID: 19041716." } }, "fdaStatus": "not-approved-us", "approvalDetails": "Not approved in the US; Drugs@FDA holds no record of somatostatin. Approved in Spain (Somatostatina GP-Pharm 3 mg) for variceal bleeding alongside other measures and for high-output pancreatic fistulas, and in Singapore (Stilamin) for severe upper gastrointestinal bleeding and fistulas, by continuous infusion of about 250 µg an hour.", "mechanism": "Binds five somatostatin receptor subtypes (SSTR1-5), all Gi/o-protein-coupled receptors. Activation inhibits adenylyl cyclase, reduces cAMP, opens K+ channels, and closes Ca2+ channels. Net effects: suppression of GH release from somatotrophs, inhibition of TSH, ACTH, insulin, glucagon, gastrin, secretin, VIP, and motilin. Also exerts antiproliferative effects via SSTR2/SSTR5 signaling, exploited in neuroendocrine tumor therapy.", "primaryUses": [ "Bleeding oesophageal varices (approved outside the US)", "Pancreatic fistulas (approved outside the US)" ], "typicalDose": { "range": "N/A", "unit": "N/A", "frequency": "N/A", "route": "endogenous", "notes": "Native somatostatin is not used therapeutically due to its ~2-minute half-life. Synthetic analogs (octreotide 100-500 mcg SC 2-3x daily; lanreotide 60-120 mg deep SC monthly) are used clinically instead." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Planas M, et al. \"Severe acute pancreatitis: treatment with somatostatin.\" Intensive Care Med, 1998;24(1):37-9. PMID: 9503220.", "pmid": "9503220" }, { "type": "pubmed", "citation": "Patel YC. \"Somatostatin and its receptor family.\" Front Neuroendocrinol, 1999;20(3):157-98. PMID: 10433861.", "pmid": "10433861" }, { "type": "pubmed", "citation": "Theodoropoulou M, et al. \"Somatostatin receptors: from signaling to clinical practice.\" Front Neuroendocrinol, 2013;34(3):228-52. PMID: 23872332.", "pmid": "23872332" }, { "type": "pubmed", "citation": "Brazeau P, et al. \"Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone.\" Science, 1973;179(4068):77-9. PMID: 4682131.", "pmid": "4682131" }, { "type": "pubmed", "citation": "Cervin C, et al. \"A combined in vitro and in vivo study on the interactions between somatostatin and lipid-based liquid crystalline drug carriers and bilayers.\" Eur J Pharm Sci, 2009;36(4-5):377-85. PMID: 19041716.", "pmid": "19041716" }, { "type": "other", "citation": "Spanish Agency of Medicines (AEMPS), Somatostatina GP-Pharm 3 mg product information (ficha técnica): variceal bleeding and pancreatic fistulas, 3.5 µg/kg per hour. Read September 30, 2026." }, { "type": "other", "citation": "Singapore National Drug Formulary, Stilamin 3000 (somatostatin) product information: upper gastrointestinal bleeding and fistulas, 250 µg then 250 µg per hour. Read September 30, 2026." }, { "type": "other", "citation": "US FDA, Drugs@FDA (openFDA): no record for somatostatin. Read September 30, 2026." } ], "interactionCoverage": "partial", "related": [ "octreotide", "lanreotide", "pasireotide", "somatropin", "ghrelin", "sermorelin" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-21", "fdaApproved": false, "approvedElsewhere": "Spain and Singapore", "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide", "statusVerified": { "date": "2026-09-30", "source": "openFDA (no record); AEMPS product information for Somatostatina GP-Pharm; Singapore NDF product information for Stilamin 3000" } }, { "id": "somatrogon", "name": "Somatrogon", "aliases": [ "Ngenla", "MOD-4023", "OPK-88003", "CTP-modified hGH", "somatrogon-ghla" ], "tier": "stub", "category": "growth-hormone", "subcategory": "once-weekly C-terminal peptide fusion growth hormone", "class": "A long-acting recombinant growth hormone fusion protein in which the C-terminal peptide (CTP) of the hCG β-subunit is fused to both the N- and C-termini of somatropin, extending half-life sufficiently for weekly dosing.", "tagline": "Pfizer/OPKO's once-weekly growth hormone (Ngenla) — FDA-approved in June 2023 for pediatric GH deficiency in children aged 3+ years; uses a CTP-fusion strategy borrowed from long-acting follitropin alfa.", "oneLiner": "A once-weekly recombinant growth hormone fusion protein in which three copies of the hCG β-subunit C-terminal peptide (CTP) — a naturally O-glycosylated 28-amino-acid sequence — are fused to the N- and C-termini of somatropin to extend plasma half-life. FDA-approved as Ngenla in June 2023 for pediatric GH deficiency in patients aged 3 years and older, following earlier EMA (2022), Canadian, Japanese, and Australian approvals. The CTP-fusion approach is the same half-life-extension technology used in long-acting follitropin alfa (choriogonadotropin alfa / corifollitropin).", "sequence": "CTP-(hGH 1-191)-CTP-CTP fusion protein; three hCG β-subunit CTP sequences flank the somatropin backbone", "molecularFormula": null, "molecularWeight": 46000, "halfLife": { "value": 28, "unit": "hours", "range": "~24–32 hours (effective weekly PK)", "notes": "Terminal half-life supports weekly dosing; steady state within approximately 3–4 weeks." }, "fdaStatus": "approved", "approvalDetails": "FDA-approved June 2023 as Ngenla (Pfizer, developed in partnership with OPKO Health) for pediatric growth hormone deficiency aged 3 years and older. Previously approved EMA (February 2022), Health Canada (October 2021), Japan, Australia, and additional markets.", "mechanism": "Binds the GH receptor with affinity comparable to native somatropin, activating JAK2/STAT5 signaling and IGF-1 production. The CTP (C-terminal peptide) domains — O-glycosylated with four negatively charged sialic acid residues per copy — shield the fusion protein from renal filtration and proteolytic clearance, extending circulating half-life. This is the same CTP-fusion technology used in long-acting follitropin alfa (Elonva) for reproductive medicine.", "primaryUses": [ "Pediatric growth hormone deficiency (age 3+)" ], "typicalDose": { "range": "0.66", "unit": "mg/kg/week", "frequency": "once weekly", "route": "subcutaneous", "notes": "Fixed weekly dosing of 0.66 mg/kg via a prefilled auto-injector pen. Patient-reported outcomes studies favored weekly somatrogon over daily somatropin on burden-of-treatment scales." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Ngenla (somatrogon-ghla) Prescribing Information. Pfizer." }, { "type": "clinical-trial", "citation": "Deal CL, et al. \"Efficacy and Safety of Weekly Somatrogon vs Daily Somatropin in Children with GH Deficiency: A Phase 3 Study.\" J Clin Endocrinol Metab, 2022;107:e2717-e2728. PMID: 35405011.", "pmid": "35405011" }, { "type": "manufacturer", "citation": "Pfizer. \"FDA approves Ngenla (somatrogon-ghla) for pediatric growth hormone deficiency.\" Press release, June 28, 2023." } ], "interactionCoverage": "label", "related": [ "somatropin", "somapacitan", "lonapegsomatropin", "sermorelin" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.2.3", "named": true, "wording": "somatrogon", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "A long-acting growth hormone analogue." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.2.3", "named": true, "wording": "somatrogon", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "A long-acting growth hormone analogue." } ], "moleculeClass": "protein", "moleculeClassBasis": "fusion protein" }, { "id": "somatropin", "name": "Somatropin (HGH)", "aliases": [ "rhGH", "HGH", "human growth hormone", "Humatrope", "Genotropin", "Norditropin", "Omnitrope", "Saizen", "Serostim", "Zomacton", "HGH 191AA", "Jintropin", "Ansomone", "Hygetropin", "Kigtropin" ], "tier": "full", "category": "growth-hormone", "subcategory": "recombinant human growth hormone", "class": "Recombinant 191-amino-acid human growth hormone, structurally identical to the pituitary hormone.", "tagline": "FDA-approved recombinant human growth hormone — the direct hormone replacement, with multiple clinical indications, prescription-only status, and specific federal criminal provisions against off-label distribution.", "oneLiner": "The 191-amino-acid recombinant form of human growth hormone, produced in E. coli (Genotropin, Humatrope) or mouse-cell expression systems, used to replace deficient GH across pediatric and adult indications and — unlike most drugs — subject to federal criminal penalties for off-label distribution under 21 U.S.C. §333(e).", "sequence": "FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF", "molecularFormula": "C990H1528N262O300S7", "molecularWeight": 22124, "halfLife": { "value": 3.5, "unit": "hours", "range": "2–5 hours (SC); shorter IV", "notes": "Subcutaneous absorption gives Tmax ~4–6 hours with bioavailability 70–80%. Daily dosing is standard; long-acting depot formulations (Ngenla, Skytrofa) extend to weekly dosing." }, "fdaStatus": "approved", "approvalDetails": "FDA-approved for: pediatric GH deficiency, adult GH deficiency, Turner syndrome, chronic renal insufficiency in children, Prader-Willi syndrome, idiopathic short stature, small-for-gestational-age children, SHOX deficiency, Noonan syndrome, short bowel syndrome (Zorbtive, daily high-dose), HIV-associated wasting (Serostim). Brand names include Humatrope (Lilly), Genotropin (Pfizer), Norditropin (Novo Nordisk), Omnitrope (Sandoz), Saizen (Merck), Zomacton (Ferring), Serostim (EMD Serono), Skytrofa (Ascendis, weekly), Ngenla (Pfizer, weekly).", "mechanism": "Binds dimerized GH receptors on target tissues, triggering JAK2/STAT5 signaling. Direct effects include lipolysis (adipocyte), gluconeogenesis and insulin antagonism (hepatic), and anabolic effects on muscle, bone, and cartilage. Indirect effects are mediated by hepatic IGF-1 production, which drives most of the somatic growth effects. Exogenous administration suppresses endogenous pulsatile secretion via negative feedback on hypothalamic somatostatin and GHRH neurons.", "primaryUses": [ "Pediatric and adult GH deficiency", "Turner syndrome", "Prader-Willi syndrome", "Chronic kidney disease in children", "HIV-associated wasting (Serostim)", "Short bowel syndrome (Zorbtive)", "Idiopathic short stature", "SHOX deficiency", "Noonan syndrome", "Off-label: anti-aging, bodybuilding (illegal under federal HGH distribution law)" ], "typicalDose": { "range": "0.15–0.7", "unit": "mg/day", "frequency": "once daily (legacy) or weekly (Skytrofa, Ngenla)", "route": "subcutaneous", "notes": "Pediatric GHD: 0.16–0.3 mg/kg/week divided daily. Adult GHD: 0.15–0.3 mg/day titrated to IGF-1 target. Bodybuilding \"anti-aging\" community use (2–4 IU/day ≈ 0.66–1.33 mg/day) is illegal under federal law and carries meaningful long-term safety concerns including insulin resistance, carpal tunnel syndrome, and accelerated growth of occult neoplasms." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Humatrope (somatropin) Prescribing Information. Eli Lilly." }, { "type": "fda-pi", "citation": "Genotropin (somatropin) Prescribing Information. Pfizer." }, { "type": "fda-pi", "citation": "Norditropin (somatropin) Prescribing Information. Novo Nordisk." }, { "type": "fda-pi", "citation": "Skytrofa (lonapegsomatropin) Prescribing Information. Ascendis Pharma." }, { "type": "review", "citation": "Molitch ME, et al. \"Evaluation and Treatment of Adult Growth Hormone Deficiency: An Endocrine Society Clinical Practice Guideline.\" J Clin Endocrinol Metab, 2011;96:1587-1609. PMID: 21602453.", "pmid": "21602453" }, { "type": "fda-pi", "citation": "21 U.S.C. §333(e). Federal HGH distribution law: specific criminal penalties for off-label distribution." }, { "type": "pubmed", "citation": "Thornton PS, et al. \"Weekly Lonapegsomatropin in Treatment-Naïve Children With Growth Hormone Deficiency: The Phase 3 heiGHt Trial.\" J Clin Endocrinol Metab, 2021;106(11):3184-3195. PMID: 34272849.", "pmid": "34272849" }, { "type": "pubmed", "citation": "Sävendahl L, et al. \"Long-term mortality after childhood growth hormone treatment: the SAGhE cohort study.\" Lancet Diabetes Endocrinol, 2020;8(8):683-692. PMID: 32707116.", "pmid": "32707116" }, { "type": "pubmed", "citation": "Melmed S. \"Pathogenesis and Diagnosis of Growth Hormone Deficiency in Adults.\" N Engl J Med, 2019;380(26):2551-2562. PMID: 31242363.", "pmid": "31242363" }, { "type": "pubmed", "citation": "Yuen KCJ, et al. \"AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY GUIDELINES FOR MANAGEMENT OF GROWTH HORMONE DEFICIENCY IN ADULTS AND PATIENTS TRANSITIONING FROM PEDIATRIC TO ADULT CARE.\" Endocr Pract, 2019;25(11):1191-1232. PMID: 31760824.", "pmid": "31760824" }, { "type": "pubmed", "citation": "Deal CL, et al. \"GrowthHormone Research Society workshop summary: consensus guidelines for recombinant human growth hormone therapy in Prader-Willi syndrome.\" J Clin Endocrinol Metab, 2013;98(6):E1072-87. PMID: 23543664.", "pmid": "23543664" }, { "type": "pubmed", "citation": "Liu H, et al. \"Systematic review: the safety and efficacy of growth hormone in the healthy elderly.\" Ann Intern Med, 2007;146(2):104-15. PMID: 17227934.", "pmid": "17227934" }, { "type": "pubmed", "citation": "Stephure DK. \"Impact of growth hormone supplementation on adult height in turner syndrome: results of the Canadian randomized controlled trial.\" J Clin Endocrinol Metab, 2005;90(6):3360-6. PMID: 15784709.", "pmid": "15784709" } ], "interactionCoverage": "partial", "related": [ "tesamorelin", "sermorelin", "cjc-1295", "ipamorelin", "mk-677", "igf-1-lr3", "aod-9604" ], "lastReviewed": "2026-04-18", "publishedAt": "2026-04-18", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.2.3", "named": true, "wording": "Growth hormone (GH), its analogues and fragments", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Approval does not exempt a substance from the List." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.2.3", "named": true, "wording": "Growth hormone (GH), its analogues and fragments", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Approval does not exempt a substance from the List." } ], "moleculeClass": "protein", "moleculeClassBasis": "191-amino-acid" }, { "id": "ss-31", "name": "SS-31 (Elamipretide)", "aliases": [ "Elamipretide", "Forzinity", "Bendavia", "MTP-131" ], "tier": "full", "category": "longevity", "subcategory": "mitochondrial-targeted peptide", "class": "A cell-permeable tetrapeptide that selectively binds cardiolipin on the inner mitochondrial membrane.", "tagline": "The first FDA-approved mitochondria-targeted peptide therapeutic — approved September 2025 as Forzinity for Barth syndrome, with broader investigation in heart failure, macular degeneration, and aging.", "oneLiner": "A 4-amino-acid aromatic-cationic peptide (D-Arg-Dmt-Lys-Phe-NH2) that concentrates in the inner mitochondrial membrane (1000-fold over cytosol) by binding cardiolipin, stabilizing mitochondrial cristae architecture and restoring ATP production — FDA-approved in 2025 for Barth syndrome.", "sequence": "H-D-Arg-Dmt-Lys-Phe-NH2", "molecularFormula": "C32H49N9O5", "molecularWeight": 639.8, "halfLife": { "value": null, "unit": null, "range": "not stated on the FORZINITY label", "notes": "The label gives no half-life: peak levels 0.5 to 1 hour after an injection under the skin, minimal accumulation with once-daily dosing, and about 100% of a dose recovered in urine within 48 hours. After a 4-hour infusion in heart failure, levels were undetectable by 24 hours (Daubert 2017). The '3–5 hours' given here before had no source." }, "fdaStatus": "approved", "approvalDetails": "FDA granted accelerated approval September 19, 2025 as Forzinity (Stealth BioTherapeutics) for improvement of muscle strength in adult and pediatric patients with Barth syndrome weighing ≥30 kg. This is the first FDA-approved mitochondria-targeted therapeutic. Continued approval contingent on confirmatory trials. Additional indications under investigation: primary mitochondrial myopathy, dry age-related macular degeneration.", "mechanism": "Selectively binds cardiolipin — a unique phospholipid found almost exclusively in the inner mitochondrial membrane — stabilizing cristae architecture and protecting the electron transport chain. Restores normal cardiolipin remodeling in Barth syndrome (where tafazzin mutations cause abnormal cardiolipin composition). Downstream effects include restored ATP synthesis, reduced reactive oxygen species generation, and preserved mitochondrial membrane potential. In Barth syndrome, this translates to improved muscle strength via restored mitochondrial function in skeletal and cardiac muscle.", "primaryUses": [ "Barth syndrome (FDA-approved, Forzinity)", "Primary mitochondrial myopathy (investigational)", "Dry age-related macular degeneration (investigational)", "Heart failure (Phase 2/3, mixed results)", "Ischemia-reperfusion injury research" ], "typicalDose": { "range": "40", "unit": "mg", "frequency": "once daily", "route": "subcutaneous", "notes": "Forzinity: 40 mg SC once daily for adult and pediatric patients ≥30 kg. Adverse events primarily injection site reactions and rare hypersensitivity." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Forzinity (elamipretide) Prescribing Information. Stealth BioTherapeutics. September 2025.", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215244s000lbl.pdf" }, { "type": "clinical-trial", "citation": "Thompson WR, et al. \"A phase 2/3 randomized clinical trial followed by an open-label extension to evaluate the effectiveness of elamipretide in Barth syndrome (TAZPOWER).\" Genet Med, 2021;23:471-478. PMID: 33077895.", "pmid": "33077895" }, { "type": "pubmed", "citation": "Birk AV, et al. \"The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin.\" J Am Soc Nephrol, 2013;24:1250-1261. PMID: 23813215.", "pmid": "23813215" }, { "type": "clinical-trial", "citation": "Butler J, et al. \"Effects of elamipretide on left ventricular function in heart failure with reduced ejection fraction: the PROGRESS-HF phase 2 trial.\" J Card Fail, 2020. PMID: 32068002.", "pmid": "32068002" }, { "type": "pubmed", "citation": "Shirley M. \"Elamipretide: First Approval.\" Drugs, 2026;86(3):377-383. PMID: 41335372.", "pmid": "41335372" }, { "type": "pubmed", "citation": "Thompson WR, et al. \"Long-term efficacy and safety of elamipretide in patients with Barth syndrome: 168-week open-label extension results of TAZPOWER.\" Genet Med, 2024;26(7):101138. PMID: 38602181.", "pmid": "38602181" }, { "type": "pubmed", "citation": "Ehlers JP, et al. \"ReCLAIM-2: A Randomized Phase II Clinical Trial Evaluating Elamipretide in Age-related Macular Degeneration, Geographic Atrophy Growth, Visual Function, and Ellipsoid Zone Preservation.\" Ophthalmol Sci, 2025;5(1):100628. PMID: 39605874.", "pmid": "39605874" }, { "type": "pubmed", "citation": "Karaa A, et al. \"Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial.\" Neurology, 2023;101(3):e238-e252. PMID: 37268435.", "pmid": "37268435" }, { "type": "pubmed", "citation": "Hornby B, et al. \"Natural history comparison study to assess the efficacy of elamipretide in patients with Barth syndrome.\" Orphanet J Rare Dis, 2022;17(1):336. PMID: 36056411.", "pmid": "36056411" } ], "interactionCoverage": "none-found", "related": [ "epithalon", "mots-c", "humanin", "foxo4-dri" ], "lastReviewed": "2026-04-18", "publishedAt": "2026-04-18", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "S0 does not apply: FDA approved elamipretide (Forzinity) in September 2025, and no section of either List names it or a class it belongs to. This row showed S0? until September 27, 2026." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "S0 does not apply: FDA approved elamipretide (Forzinity) in September 2025, and no section of either List names it or a class it belongs to. This row showed S0? until September 27, 2026." } ], "moleculeClass": "peptide", "statusVerified": { "date": "2026-09-30", "source": "US FDA, Drugs@FDA (openFDA): FORZINITY (elamipretide), Stealth BioTherapeutics, NDA 215244, prescription, 280 mg/3.5 mL solution. Approval details on the entry match the record." } }, { "id": "substance-p", "name": "Substance P", "aliases": [ "SP", "Neurokinin 1", "NK1 ligand" ], "tier": "mid", "category": "immune", "subcategory": "neuropeptide / neuroinflammatory mediator", "class": "An 11-amino-acid neuropeptide of the tachykinin family, functioning as the primary endogenous ligand for the NK1 receptor, with roles in pain transmission, neuroinflammation, nausea, and mood.", "tagline": "The pain neuropeptide of the NK1 receptor: infusing it gave 71% of healthy adults a headache, and blocking it failed as a painkiller.", "oneLiner": "A tachykinin neuropeptide released by sensory nerves that drives pain signalling and neurogenic inflammation through the NK1 receptor.", "sequence": "Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2", "molecularFormula": "C63H98N18O13S", "molecularWeight": 1347.6, "halfLife": { "value": null, "unit": null, "range": "not measured in people in the sources read", "source": { "type": "none", "note": "searched PubMed on September 30, 2026; no human half-life reported in the sources read" } }, "fdaStatus": "research-only", "approvalDetails": "Not a medicine anywhere; no application appears in Drugs@FDA. The NK1 receptor blocker aprepitant is approved separately as Emend (NDA 021549) against chemotherapy-induced nausea and vomiting.", "mechanism": "Binds the NK1 receptor (neurokinin 1, a Gq-coupled GPCR) in the dorsal horn (pain transmission), area postrema/NTS (emesis), amygdala/hypothalamus (stress/anxiety), and peripheral sensory nerves (neurogenic inflammation — vasodilation, plasma extravasation, mast cell degranulation). Released from C-fiber nerve terminals in an axon reflex pattern. Also activates NK2 and NK3 at high concentrations.", "primaryUses": [ "Experimental challenge agent (research)" ], "typicalDose": { "range": null, "unit": null, "frequency": null, "route": null, "notes": "Endogenous neuropeptide. Not administered therapeutically. NK1 antagonists are the therapeutic class." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Al-Khazali HM, et al. \"Effects of substance P on headache induction and arterial dilation in healthy adults.\" Cephalalgia, 2025;45(5):3331024251336132. PMID: 40369974.", "pmid": "40369974" }, { "type": "pubmed", "citation": "Ten Voorde W, et al. \"Intradermal substance P as a challenge agent in healthy individuals.\" Clin Transl Sci, 2023;16(10):1856-1865. PMID: 37547990.", "pmid": "37547990" }, { "type": "pubmed", "citation": "Coiro V, et al. \"Luteinizing hormone response to an intravenous infusion of substance P in normal men.\" Metabolism, 1992;41(7):689-91. PMID: 1377769.", "pmid": "1377769" }, { "type": "pubmed", "citation": "Kwon M, et al. \"Substance P-neurokinin 1 receptor signal involves the development of osteoarthritis-induced chronic pain in rats.\" J Neuropathol Exp Neurol, 2025;84(10):879-891. PMID: 40613647.", "pmid": "40613647" }, { "type": "pubmed", "citation": "Hill R. \"NK1 (substance P) receptor antagonists--why are they not analgesic in humans?.\" Trends Pharmacol Sci, 2000;21(7):244-6. PMID: 10871891.", "pmid": "10871891" }, { "type": "pubmed", "citation": "Mantyh PW. \"Neurobiology of substance P and the NK1 receptor.\" J Clin Psychiatry, 2002;63 Suppl 11:6-10. PMID: 12562137.", "pmid": "12562137" }, { "type": "pubmed", "citation": "Steinhoff MS, et al. \"Tachykinins and their receptors: contributions to physiological control and the mechanisms of disease.\" Physiol Rev, 2014;94(1):265-301. PMID: 24382888.", "pmid": "24382888" }, { "type": "fda-pi", "citation": "EMEND (fosaprepitant) for injection Prescribing Information, section 1 (DailyMed version 20, effective February 20, 2026; read September 30, 2026)." }, { "type": "other", "citation": "US FDA, Drugs@FDA (openFDA): no application for substance P; EMEND (aprepitant), NDA 021549, Merck Sharp & Dohme. Read September 30, 2026." } ], "interactionCoverage": "unreviewed", "related": [ "vip", "alpha-msh", "kpv" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-20", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "survodutide", "name": "Survodutide", "aliases": [ "BI 456906" ], "tier": "full", "category": "metabolic", "subcategory": "GLP-1/glucagon dual agonist", "class": "Investigational dual agonist at GLP-1 and glucagon receptors.", "tagline": "A once-weekly glucagon/GLP-1 dual agonist: about 13% weight loss at 76 weeks in phase 3 and MASH improvement in phase 2, but not yet approved anywhere.", "oneLiner": "A synthetic, fatty-acid-acylated peptide (BI 456906) that activates the glucagon and GLP-1 receptors, modelled on oxyntomodulin and dosed once weekly; its phase 3 obesity and liver-fat trials reported in 2026.", "sequence": null, "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": null, "range": "long enough for weekly dosing; not reported in the abstracts we hold", "notes": "A C18 fatty acid binds albumin to extend its action (2022 discovery paper). The '~7 days' given here before had no source." }, "fdaStatus": "clinical-trials", "approvalDetails": "Investigational; not approved anywhere as of September 27, 2026. Developed by Boehringer Ingelheim under licence from Zealand Pharma. FDA Fast Track (May 2021) and Breakthrough Therapy (September 2024) designations, as the company reported. Phase 3: SYNCHRONIZE-1 (obesity, reported 2026) and SYNCHRONIZE-MASLD (2026) met their primary endpoints; SYNCHRONIZE-2 (with type 2 diabetes) and SYNCHRONIZE-CVOT are the next readouts.", "mechanism": "Dual agonism at GLP-1 and glucagon receptors. GLP-1 drives insulin release, glucagon suppression during hyperglycemia, gastric emptying delay, and central appetite suppression. Glucagon activation increases hepatic lipolysis, hepatic glucose output during hypoglycemia, and energy expenditure — a combination particularly relevant for liver fat reduction in MASH.", "primaryUses": [ "Obesity — Phase 3", "Type 2 diabetes — Phase 3", "MASH — Phase 3 (Breakthrough Therapy)" ], "typicalDose": { "range": "2.4–6.0", "unit": "mg", "frequency": "weekly", "route": "subcutaneous", "notes": "Trial maintenance doses after 16-24 weeks of escalation; phase 3 obesity trials use up to 3.6 or 6.0 mg. No approved dose." }, "evidenceLevel": "high", "sources": [ { "type": "Animal", "citation": "Zimmermann T, et al. \"BI 456906: Discovery and preclinical pharmacology of a novel GCGR/GLP-1R dual agonist with robust anti-obesity efficacy.\" Mol Metab, 2022;66:101633. PMID: 36356832.", "pmid": "36356832" }, { "type": "Human", "citation": "Jungnik A, et al. \"Phase I studies of the safety, tolerability, pharmacokinetics and pharmacodynamics of the dual glucagon receptor/glucagon-like peptide-1 receptor agonist BI 456906.\" Diabetes Obes Metab, 2023;25(4):1011-1023. PMID: 36527386.", "pmid": "36527386" }, { "type": "Human", "citation": "Yazawa R, et al. \"A randomized Phase I study of the safety, tolerability, pharmacokinetics and pharmacodynamics of BI 456906, a dual glucagon receptor/glucagon-like peptide-1 receptor agonist, in healthy Japanese men with overweight/obesity.\" Diabetes Obes Metab, 2023;25(7):1973-1984. PMID: 36974349.", "pmid": "36974349" }, { "type": "Human", "citation": "le Roux CW, et al. \"Glucagon and GLP-1 receptor dual agonist survodutide for obesity: a randomised, double-blind, placebo-controlled, dose-finding phase 2 trial.\" Lancet Diabetes Endocrinol, 2024;12(3):162-173. PMID: 38330987.", "pmid": "38330987" }, { "type": "Human", "citation": "Blüher M, et al. \"Dose-response effects on HbA(1c) and bodyweight reduction of survodutide, a dual glucagon/GLP-1 receptor agonist, compared with placebo and open-label semaglutide in people with type 2 diabetes: a randomised clinical trial.\" Diabetologia, 2024;67(3):470-482. PMID: 38095657.", "pmid": "38095657" }, { "type": "Human", "citation": "Sanyal AJ, et al. \"A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis.\" N Engl J Med, 2024;391(4):311-319. PMID: 38847460.", "pmid": "38847460" }, { "type": "Human", "citation": "Lawitz EJ, et al. \"Efficacy, tolerability and pharmacokinetics of survodutide, a glucagon/glucagon-like peptide-1 receptor dual agonist, in cirrhosis.\" J Hepatol, 2024;81(5):837-846. PMID: 38857788.", "pmid": "38857788" }, { "type": "Animal", "citation": "Thomas L, et al. \"The dual GCGR/GLP-1R agonist survodutide: Biomarkers and pharmacological profiling for clinical candidate selection.\" Diabetes Obes Metab, 2024;26(6):2368-2378. PMID: 38560764.", "pmid": "38560764" }, { "type": "Review", "citation": "Kaya E, et al. \"Survodutide in MASH: bridging the gap between hepatic and systemic metabolic dysfunction.\" Expert Opin Investig Drugs, 2024;33(12):1167-1176. PMID: 39663847.", "pmid": "39663847" }, { "type": "Human", "citation": "le Roux CW, et al. \"Subgroup analysis by sex and baseline BMI in people with a BMI ≥27 kg/m(2) in the phase 2 trial of survodutide, a glucagon/GLP-1 receptor dual agonist.\" Diabetes Obes Metab, 2025;27(4):1773-1782. PMID: 39821928.", "pmid": "39821928" }, { "type": "Human", "citation": "le Roux CW, et al. \"Survodutide Once Weekly for the Treatment of Adults with Obesity.\" N Engl J Med, 2026;395(8):776-787. PMID: 42253238.", "pmid": "42253238" }, { "type": "Human", "citation": "Kaplan LM, et al. \"Survodutide in adults with obesity and metabolic dysfunction-associated steatotic liver disease: SYNCHRONIZE-MASLD, a randomized, double-blind, placebo-controlled phase 3 trial.\" Nat Med, 2026;32(8):2948-2958. PMID: 42252333.", "pmid": "42252333" }, { "type": "Human", "citation": "le Roux CW, et al. \"Survodutide for treatment of obesity: Baseline characteristics of participants in a randomized, double-blind, placebo-controlled, phase 3 trial (SYNCHRONIZE™-1).\" Diabetes Obes Metab, 2026;28(1):337-346. PMID: 41187967.", "pmid": "41187967" }, { "type": "Human", "citation": "Wharton S, et al. \"Baseline characteristics in the SYNCHRONIZE™-2 randomized phase 3 trial of survodutide, a glucagon receptor/GLP-1 receptor dual agonist, for obesity in people with type 2 diabetes.\" Diabetes Obes Metab, 2026;28(2):1490-1498. PMID: 41216778.", "pmid": "41216778" }, { "type": "Human", "citation": "Ekinci EI, et al. \"Dual Glucagon and GLP-1 Receptor Agonist Survodutide Improves Biomarkers of Beta-Cell Function and Insulin Sensitivity in People With Type 2 Diabetes or Living With Overweight/Obesity.\" Diabetes Obes Metab, 2026;28(9):8242-8253. PMID: 42331726.", "pmid": "42331726" }, { "type": "clinical-trial", "citation": "Boehringer Ingelheim. SYNCHRONIZE-1: survodutide in adults with obesity without type 2 diabetes (phase 3). ClinicalTrials.gov NCT06066515; results published 2026." } ], "interactionCoverage": "studied", "related": [ "retatrutide", "mazdutide", "semaglutide" ], "lastReviewed": "2026-09-27", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." } ], "moleculeClass": "peptide" }, { "id": "syn-ake", "name": "Syn-Ake", "aliases": [ "Dipeptide Diaminobutyroyl Benzylamide Diacetate", "β-Ala-Pro-Dab-NHBn·2AcOH" ], "tier": "stub", "category": "cosmetic", "subcategory": "topical cosmetic peptide (Waglerin-1 mimic)", "class": "A synthetic tripeptide analog modeled on Waglerin-1, a component of temple viper venom, formulated as a topical cosmetic ingredient.", "tagline": "A \"snake-venom mimetic\" cosmetic tripeptide modeled on Waglerin-1 (Tropidolaemus wagleri venom) — blocks post-synaptic acetylcholine receptors rather than acting pre-synaptically like Argireline; modest reductions in expression-line depth in manufacturer studies.", "oneLiner": "A synthetic tripeptide analog of Waglerin-1 (a Tropidolaemus wagleri temple-viper venom peptide), developed by Pentapharm/DSM as a topical cosmetic ingredient that antagonizes the muscle-type nicotinic acetylcholine receptor post-synaptically to produce a mild, localized relaxation of facial expression muscles.", "sequence": "β-Ala-Pro-Dab-NHBn (N-benzylated tripeptide analog)", "molecularFormula": "C18H27N5O2 (free base)", "molecularWeight": 361.44, "halfLife": { "value": null, "unit": null, "range": "topical only", "notes": "Systemic absorption from topical cosmetic formulations is minimal." }, "fdaStatus": "research-only", "approvalDetails": "Cosmetic ingredient; not a drug. Widely used in topical anti-aging formulations since the mid-2000s.", "mechanism": "Designed to mimic the action of Waglerin-1 on the muscle-type nicotinic acetylcholine receptor — competitive antagonism at the post-synaptic receptor blocks acetylcholine-driven muscle contraction. This mechanism is complementary to Argireline, which acts pre-synaptically on SNAP-25; the two are often combined in formulations on the claim that pre- and post-synaptic blockade is additive.", "primaryUses": [ "Topical cosmetic anti-aging formulations (expression-line reduction)" ], "typicalDose": { "range": "4", "unit": "% (topical formulation)", "frequency": "daily topical application", "route": "topical", "notes": "Manufacturer-recommended usage concentration." }, "evidenceLevel": "low", "sources": [ { "type": "manufacturer", "citation": "Pentapharm / DSM. \"Syn-Ake technical data sheet and cosmetic ingredient profile.\"" }, { "type": "pubmed", "citation": "Schürer N, et al. \"Waglerin analog peptide in topical cosmetic formulation: effect on expression-line depth.\" Int J Cosmet Sci, 2008;30(4):297-306." } ], "interactionCoverage": "unreviewed", "related": [ "argireline", "snap-8", "matrixyl" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." } ], "moleculeClass": "peptidomimetic", "moleculeClassBasis": "tripeptide analog" }, { "id": "tabimorelin", "name": "Tabimorelin", "aliases": [ "NN703", "NNC 26-0703" ], "tier": "stub", "category": "pipeline", "subcategory": "discontinued oral ghrelin receptor agonist", "class": "An early small-molecule orally active ghrelin receptor (GHS-R1a) agonist developed in the late 1990s / early 2000s by Novo Nordisk as an oral GH secretagogue candidate.", "tagline": "Novo Nordisk's discontinued oral GH secretagogue — evaluated in Phase 2 for adult GH deficiency in the late 1990s and early 2000s; discontinued for commercial/strategic reasons. Relevant today as a historical archetype alongside MK-677 and capromorelin.", "oneLiner": "An early small-molecule orally active ghrelin receptor (GHS-R1a) agonist developed by Novo Nordisk in the late 1990s and early 2000s as an oral GH secretagogue candidate for adult GH deficiency and elderly somatopause indications. Produced dose-dependent increases in GH and IGF-1 in Phase 2 but was discontinued for commercial/strategic reasons before advancing to Phase 3. Included for reference as a historical archetype of the oral-ghrelin-agonist class alongside MK-677 (ibutamoren), capromorelin, and anamorelin.", "sequence": null, "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": "hours", "range": "once-daily dosing feasible", "notes": "Historical data; detailed PK parameters not widely published." }, "fdaStatus": "discontinued", "approvalDetails": "Not approved. Novo Nordisk discontinued development in the early 2000s. No current active program.", "mechanism": "Agonism at the ghrelin receptor (GHS-R1a) in hypothalamus and pituitary, producing pulsatile GH release through the same pathway as MK-677 and the peptidic GHRPs. As with other GHS agonists, chronic administration produces moderate increases in IGF-1.", "primaryUses": [ "Historical: adult growth hormone deficiency (investigational)", "Historical: elderly somatopause (investigational)" ], "typicalDose": { "range": null, "unit": null, "frequency": null, "route": null, "notes": "Not available for any current use." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Svensson J, et al. \"Two-month treatment of obese subjects with the oral growth hormone (GH) secretagogue MK-677 increases GH secretion, fat-free mass, and energy expenditure.\" J Clin Endocrinol Metab, 1998;83:362-369 (citing tabimorelin among early orally active GHS candidates). PMID: 9467542.", "pmid": "9467542" }, { "type": "manufacturer", "citation": "Novo Nordisk NN703 clinical program; development discontinued. Referenced in industry pharmacology reviews of oral GH secretagogues." } ], "interactionCoverage": "studied", "related": [ "mk-677", "anamorelin", "capromorelin", "macimorelin" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.2.4", "named": true, "wording": "tabimorelin", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.2.4", "named": true, "wording": "tabimorelin", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "small-molecule", "moleculeClassBasis": "small-molecule" }, { "id": "taldefgrobep-alfa", "name": "Taldefgrobep alfa", "aliases": [ "BMS-986089", "BHV-2000" ], "tier": "stub", "category": "pipeline", "subcategory": "anti-myostatin adnectin", "class": "A recombinant Fc-fused anti-myostatin adnectin protein (not a full antibody), originally developed by Bristol-Myers Squibb and licensed to Biohaven.", "tagline": "A Biohaven (ex-BMS) myostatin-binding adnectin-Fc fusion — RESILIENT Phase 3 trial in spinal muscular atrophy missed its primary endpoint (December 2024); further development pivoted toward obesity and sarcopenia indications.", "oneLiner": "A recombinant anti-myostatin adnectin fused to a human Fc domain, originally BMS-986089, now developed by Biohaven as BHV-2000; the RESILIENT Phase 3 trial in spinal muscular atrophy missed its primary endpoint in December 2024, and subsequent development is focused on obesity and sarcopenia indications where the muscle-sparing profile is more commercially relevant.", "sequence": null, "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": "days", "range": "days to weeks (Fc-mediated)", "notes": "Fc-extended half-life; Phase 3 dosing was weekly SC." }, "fdaStatus": "clinical-trials", "approvalDetails": "Not approved. Biohaven reported in December 2024 that RESILIENT, the Phase 3 trial in spinal muscular atrophy, missed its primary endpoint on the Motor Function Measure-32. Development continues in obesity (as a muscle-sparing GLP-1 adjunct) and other muscle-wasting conditions.", "mechanism": "The adnectin domain binds myostatin (GDF-8) with high affinity and blocks engagement with ActRIIB receptors; the Fc fusion extends circulating half-life and supports subcutaneous dosing. Adnectins are single-domain engineered proteins derived from the tenth fibronectin type III domain — a non-antibody binding scaffold.", "primaryUses": [ "Spinal muscular atrophy (Phase 3 — missed primary endpoint)", "Obesity (Phase 2 muscle-sparing combination)", "Sarcopenia (investigational)" ], "typicalDose": { "range": "not publicly disclosed", "unit": "mg", "frequency": "weekly (trial protocols)", "route": "subcutaneous", "notes": "RESILIENT Phase 3 used weekly SC administration." }, "evidenceLevel": "low", "sources": [ { "type": "manufacturer", "citation": "Biohaven Pharmaceuticals. \"RESILIENT Phase 3 topline results for taldefgrobep alfa in spinal muscular atrophy,\" corporate press release, December 2024." }, { "type": "clinical-trial", "citation": "ClinicalTrials.gov identifier for the RESILIENT Phase 3 trial in SMA." } ], "interactionCoverage": "none-found", "related": [ "bimagrumab", "trevogrumab", "apitegromab" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S4.3", "named": false, "wording": "Myostatin inhibitors", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "An anti-myostatin adnectin: S4.3 prohibits myostatin inhibitors." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S4.3", "named": false, "wording": "Myostatin inhibitors", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "An anti-myostatin adnectin: S4.3 prohibits myostatin inhibitors." } ], "moleculeClass": "protein", "moleculeClassBasis": "protein" }, { "id": "taspoglutide", "name": "Taspoglutide", "aliases": [ "BIM51077", "R1583", "RO5073031" ], "tier": "stub", "category": "pipeline", "subcategory": "long-acting GLP-1 agonist (discontinued)", "class": "A long-acting GLP-1 analog bearing two α-aminoisobutyric acid (Aib) substitutions at positions 8 and 35 for DPP-4 and proteolytic resistance.", "tagline": "A once-weekly GLP-1 RA co-developed by Ipsen and Roche — Phase 3 halted in 2010 after unacceptably high rates of injection-site reactions and hypersensitivity (including systemic allergic reactions), making it the most prominent immunogenicity-driven failure in the GLP-1 class.", "oneLiner": "A once-weekly GLP-1 receptor agonist (98% homology with native GLP-1, Aib8/Aib35 for DPP-4 resistance) developed by Ipsen and licensed to Roche in 2006; Phase 3 T-EMERGE program was suspended in September 2010 after unacceptably high rates of injection-site reactions, nausea/vomiting leading to discontinuation, and systemic hypersensitivity reactions, and development was formally terminated in 2011 — the archetypal cautionary tale for GLP-1 formulation-driven immunogenicity.", "sequence": "H-Aib-EGTFTSDVSSYLEGQAAKEFIAWLVKG-Aib-G-OH (Aib at positions 8 and 35)", "molecularFormula": "C152H229N39O45", "molecularWeight": 3312, "halfLife": { "value": null, "unit": "days", "range": "~7 days (formulation-dependent)", "notes": "Sustained-release zinc-based formulation produced prolonged absorption." }, "fdaStatus": "discontinued", "approvalDetails": "Not approved. Phase 3 T-EMERGE program halted September 2010; development formally terminated 2011. Roche returned rights to Ipsen.", "mechanism": "GLP-1 receptor agonism. The two Aib substitutions conferred DPP-4 resistance, and a zinc-based depot formulation produced once-weekly pharmacokinetics. The failure mode was immunogenic: antibody formation — possibly accelerated by the zinc-depot formulation — produced both injection-site reactions and, in a subset, systemic hypersensitivity.", "primaryUses": [ "Historical: type 2 diabetes mellitus (Phase 3)" ], "typicalDose": { "range": "10–20", "unit": "mg", "frequency": "once weekly", "route": "subcutaneous", "notes": "Phase 3 arms were 10 mg and 20 mg once weekly." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Bergenstal RM, et al. \"Efficacy and safety of taspoglutide versus sitagliptin for type 2 diabetes mellitus (T-emerge 4 trial).\" Diabetes Ther, 2012;3(1):13. PMID: 23138449.", "pmid": "23138449" }, { "type": "pubmed", "citation": "Kapitza C, et al. \"The effect of the once-weekly glucagon-like peptide-1 receptor agonist taspoglutide on postprandial glycemia.\" Diabetes Obes Metab, 2009;11:929-936." }, { "type": "manufacturer", "citation": "Roche. Media release: discontinuation of T-EMERGE Phase 3 program, September 2010." } ], "interactionCoverage": "studied", "related": [ "exenatide", "liraglutide", "dulaglutide" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "A discontinued drug: S0's own examples include discontinued drugs." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "A discontinued drug: S0's own examples include discontinued drugs." } ], "moleculeClass": "peptide" }, { "id": "tb-500", "name": "TB-500", "aliases": [ "Thymosin beta-4 fragment", "Tβ4 fragment", "TMSB4X peptide" ], "tier": "full", "category": "healing", "subcategory": "thymosin β4 fragment", "class": "Synthetic peptide fragment of thymosin β4, a naturally occurring 44-amino-acid regenerative peptide.", "tagline": "A synthetic fragment of thymosin β4 studied in animal models for actin-binding-mediated tissue repair, particularly in cardiac and soft-tissue injury.", "oneLiner": "A shortened synthetic analog of the natural regenerative peptide thymosin β4 (Tβ4), sharing its actin-binding motif but differing in structure and systemic activity.", "sequence": "LKKTETQ (the actin-binding active motif of full Tβ4)", "molecularFormula": "C38H68N10O13", "molecularWeight": 889, "halfLife": { "value": null, "unit": null, "range": "undetermined in humans", "notes": "Full thymosin β4 has a short plasma half-life (~1 hour); TB-500 fragment pharmacokinetics are not well-characterized in published human data." }, "fdaStatus": "research-only", "approvalDetails": "Not approved by any regulatory body for any indication. Full-length thymosin β4 has been tested in registered trials, as eye drops (RGN-259) and intravenously in a phase 1 safety study, but TB-500 as marketed in the peptide community is the short synthetic fragment, not full Tβ4.", "mechanism": "Binds G-actin and modulates cytoskeletal dynamics, cell migration, and angiogenesis. Preclinical studies show effects on endothelial cell migration, tissue revascularization, and inflammation modulation. Often combined with BPC-157 in community protocols for soft-tissue injuries despite absence of clinical trials.", "primaryUses": [ "Soft tissue injury (animal models)", "Cardiac repair (preclinical Tβ4 studies)", "Corneal wound healing (Tβ4 clinical trials)", "Equine veterinary use" ], "typicalDose": { "range": "2–2.5", "unit": "mg", "frequency": "1–2x weekly loading, then weekly maintenance", "route": "subcutaneous", "notes": "Community dosing. No human clinical trial has established a TB-500-specific dose." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Ruff D, et al. \"A randomized, placebo-controlled, single and multiple dose study of intravenous thymosin beta4 in healthy volunteers.\" Ann N Y Acad Sci, 2010;1194:223-9. PMID: 20536472.", "pmid": "20536472" }, { "type": "pubmed", "citation": "Guarnera G, et al. \"Thymosin beta-4 and venous ulcers: clinical remarks on a European prospective, randomized study on safety, tolerability, and enhancement on healing.\" Ann N Y Acad Sci, 2007;1112:407-12. PMID: 17495250.", "pmid": "17495250" }, { "type": "review", "citation": "Sosne G. \"Thymosin beta 4 and the eye: the journey from bench to bedside.\" Expert Opin Biol Ther, 2018;18(sup1):99-104. PMID: 30063853.", "pmid": "30063853" }, { "type": "review", "citation": "Goldstein AL, et al. \"Thymosin β4: a multi-functional regenerative peptide. Basic properties and clinical applications.\" Expert Opin Biol Ther, 2012;12(1):37-51. PMID: 22074294.", "pmid": "22074294" }, { "type": "review", "citation": "Crockford D, et al. \"Thymosin beta4: structure, function, and biological properties supporting current and future clinical applications.\" Ann N Y Acad Sci, 2010;1194:179-89. PMID: 20536467.", "pmid": "20536467" }, { "type": "review", "citation": "Bjørklund G, et al. \"Thymosin β4: A Multi-Faceted Tissue Repair Stimulating Protein in Heart Injury.\" Curr Med Chem, 2020;27(37):6294-6305. PMID: 31333080.", "pmid": "31333080" }, { "type": "review", "citation": "Pipes GT, et al. \"Cardioprotection by Thymosin Beta 4.\" Vitam Horm, 2016;102:209-26. PMID: 27450736.", "pmid": "27450736" }, { "type": "review", "citation": "Chopp M, et al. \"Thymosin β4 as a restorative/regenerative therapy for neurological injury and neurodegenerative diseases.\" Expert Opin Biol Ther, 2015;15 Suppl 1:S9-12. PMID: 25613458.", "pmid": "25613458" }, { "type": "pubmed", "citation": "Yu FX, et al. \"Thymosin beta 10 and thymosin beta 4 are both actin monomer sequestering proteins.\" J Biol Chem, 1993;268(1):502-9. PMID: 8416954.", "pmid": "8416954" }, { "type": "pubmed", "citation": "Srivastava D, et al. \"Thymosin beta4 is cardioprotective after myocardial infarction.\" Ann N Y Acad Sci, 2007;1112:161-70. PMID: 17600280.", "pmid": "17600280" }, { "type": "clinical-trial", "citation": "ReGenTree. \"Assessment of the Safety and Efficacy of RGN-259 Ophthalmic Solutions for Dry Eye Syndrome\" (phase 3, thymosin β4 eye drops). ClinicalTrials.gov NCT03937882; completed October 7, 2021." } ], "interactionCoverage": "partial", "related": [ "bpc-157", "ghk-cu" ], "lastReviewed": "2026-07-17", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.3", "named": true, "wording": "Thymosin-ß4 and its derivatives e.g. TB-500", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.3", "named": true, "wording": "Thymosin-ß4 and its derivatives e.g. TB-500", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "teduglutide", "name": "Teduglutide", "aliases": [ "Gattex", "Revestive", "ALX-0600" ], "tier": "mid", "category": "metabolic", "subcategory": "GLP-2 analog (FDA-approved)", "class": "A recombinant DPP-4-resistant analog of human glucagon-like peptide-2 (GLP-2) in which alanine at position 2 is replaced by glycine.", "tagline": "FDA-approved GLP-2 analog (Gattex/Revestive, 2012) for short-bowel syndrome — the first disease-modifying treatment for SBS, reducing parenteral nutrition dependence by promoting intestinal mucosal growth.", "oneLiner": "A DPP-4-resistant analog of GLP-2 (alanine-2 → glycine substitution) with a half-life extended from ~7 minutes for native GLP-2 to approximately 2 hours — FDA-approved 2012 as Gattex (Takeda, US) and Revestive (EU) for adult and pediatric short-bowel syndrome (SBS) patients dependent on parenteral nutrition. Mechanism is direct intestinotrophic: enterocyte proliferation, villous height increase, and crypt depth expansion, which together improve nutrient absorption and reduce PN requirements.", "sequence": "HGDGSFSDEMNTILDNLAARDFINWLIQTKITD (native GLP-2 with Ala→Gly at position 2)", "molecularFormula": "C164H252N44O55S", "molecularWeight": 3752, "halfLife": { "value": 1.3, "unit": "hours", "range": "about 2 hours in healthy subjects and 1.3 hours in people with short bowel syndrome (label 12.3)", "source": { "type": "label", "ref": "Gattex (teduglutide) prescribing information, sections 1, 2, 4, 5, 6 and 12.3 (DailyMed SPL version 20, effective September 5, 2025; read October 1, 2026)" } }, "fdaStatus": "approved", "approvalDetails": "Gattex, NDA 203441, approved December 21, 2012, for short bowel syndrome in patients dependent on parenteral support; the current label covers adults and children one year and older (Drugs@FDA and the label, read October 1, 2026).", "mechanism": "GLP-2 receptor agonism on intestinal enteroendocrine L-cells, subepithelial myofibroblasts, and enteric neurons. Drives epithelial proliferation, villous height increase, crypt depth expansion, and enhanced intestinal blood flow. In SBS this translates into improved nutrient absorption and reduced parenteral nutrition volume requirements.", "primaryUses": [ "Short-bowel syndrome (adults and pediatric ≥1 year) — FDA-approved" ], "typicalDose": { "range": "0.05", "unit": "mg/kg", "frequency": "once daily", "route": "subcutaneous", "notes": "Gattex label: 0.05 mg/kg once daily by subcutaneous injection for adults and children one year and older, rotating abdomen, thighs or arms; colonoscopy and upper endoscopy within 6 months before starting in adults, faecal occult blood testing in children; baseline bilirubin, alkaline phosphatase, lipase and amylase." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Gattex (teduglutide) prescribing information, sections 1, 2, 4, 5, 6 and 12.3 (DailyMed SPL version 20, effective September 5, 2025; read October 1, 2026)." }, { "type": "pubmed", "citation": "Jeppesen PB, et al. \"Randomised placebo-controlled trial of teduglutide in reducing parenteral nutrition and/or intravenous fluid requirements in patients with short bowel syndrome.\" Gut, 2011;60(7):902-14. PMID: 21317170.", "pmid": "21317170" }, { "type": "pubmed", "citation": "Jeppesen PB, et al. \"Teduglutide reduces need for parenteral support among patients with short bowel syndrome with intestinal failure.\" Gastroenterology, 2012;143(6):1473-1481.e3. PMID: 22982184.", "pmid": "22982184" }, { "type": "pubmed", "citation": "Chiba M, et al. \"Efficacy and Safety of Teduglutide in Infants and Children With Short Bowel Syndrome Dependent on Parenteral Support.\" J Pediatr Gastroenterol Nutr, 2023;77(3):339-346. PMID: 37364133.", "pmid": "37364133" }, { "type": "pubmed", "citation": "Joly F, et al. \"Real-world experience of Teduglutide use in adults with short bowel syndrome: A seven-year international multicenter survey.\" Clin Nutr, 2025;47:54-67. PMID: 39986179.", "pmid": "39986179" }, { "type": "pubmed", "citation": "Yeh DD, et al. \"Teduglutide for the treatment of low-output enterocutaneous fistula - A pilot randomized controlled study.\" Clin Nutr ESPEN, 2022;50:49-55. PMID: 35871951.", "pmid": "35871951" } ], "interactionCoverage": "label", "related": [ "apraglutide", "glepaglutide", "pb-718" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "teriparatide", "name": "Teriparatide", "aliases": [ "Forteo", "Bonsity", "rhPTH(1-34)", "PTH 1-34" ], "tier": "mid", "category": "healing", "subcategory": "parathyroid hormone analog (bone anabolic)", "class": "A recombinant 34-residue N-terminal fragment of human parathyroid hormone, FDA-approved as the first and prototypical anabolic osteoporosis therapy.", "tagline": "The first 34 amino acids of parathyroid hormone, injected at 20 micrograms once a day to build bone. Approved as Forteo for osteoporosis at high fracture risk: in the 1,360-woman VERO trial, new spine fractures occurred in 5.4% against 12.0% on risedronate over two years. Fracture-healing trials found no clear benefit.", "oneLiner": "Recombinant human PTH(1-34), the active fragment of parathyroid hormone, injected at 20 micrograms once daily. The daily pulse builds bone, where continuous exposure to the same hormone removes it; approved as Forteo and as follow-on products.", "sequence": "SVSEIQLMHNLGKHLNSMERVEWLRKKLQDVHNF", "molecularFormula": "C181H291N55O51S2", "molecularWeight": 4117.72, "halfLife": { "value": 1, "unit": "hours", "range": "about 1 hour after subcutaneous injection", "notes": "Very short plasma half-life — the intermittent, pulsatile exposure is central to the anabolic mechanism; continuous PTH elevation (as in primary hyperparathyroidism) is catabolic for bone.", "source": { "type": "label", "ref": "Forteo prescribing information, section 12.3 (DailyMed version 44, effective August 3, 2026; read September 30, 2026)" } }, "fdaStatus": "approved", "approvalDetails": "Approved in the US as Forteo (teriparatide injection), with follow-on products; listed as prescription drugs on Drugs@FDA (openFDA, read September 30, 2026).", "mechanism": "Binds the PTH1 receptor (PTHR1), a class B GPCR on osteoblasts and osteocytes. Intermittent, pulsatile receptor activation (from once-daily injection followed by rapid clearance) favors osteoblast lifespan and bone formation, whereas sustained PTH elevation (as in hyperparathyroidism or continuous infusion) predominantly stimulates osteoclast activity via RANKL and produces net bone loss. The anabolic-vs-catabolic duality is a key pharmacological principle for the PTH analog class.", "primaryUses": [ "Osteoporosis at high fracture risk (FDA-approved)", "Fracture healing (trials found no clear benefit)" ], "typicalDose": { "range": "20", "unit": "mcg", "frequency": "once daily", "route": "subcutaneous", "notes": "The dose used in the osteoporosis and fracture-healing trials; the label limits treatment duration." }, "evidenceLevel": "high", "sources": [ { "type": "fda", "citation": "FDA. Drugs@FDA (openFDA): FORTEO (teriparatide) injection and follow-on teriparatide products, prescription. Read September 30, 2026." }, { "type": "pubmed", "citation": "Kendler DL, et al. \"Effects of teriparatide and risedronate on new fractures in post-menopausal women with severe osteoporosis (VERO): a multicentre, double-blind, double-dummy, randomised controlled trial.\" Lancet, 2018;391(10117):230-240. PMID: 29129436.", "pmid": "29129436" }, { "type": "pubmed", "citation": "Hald JD, et al. \"Teriparatide Plus Zoledronic Acid for Osteogenesis Imperfecta: A Randomized Clinical Trial.\" JAMA, 2026;336(2):116-124. PMID: 42133304.", "pmid": "42133304" }, { "type": "pubmed", "citation": "Tripto-Shkolnik L, et al. \"Oral daily PTH(1-34) tablets (EB613) in postmenopausal women with low BMD or osteoporosis: a randomized, placebo-controlled, 6-month, phase 2 study.\" J Bone Miner Res, 2024;39(6):672-682. PMID: 38578978.", "pmid": "38578978" }, { "type": "pubmed", "citation": "Nieves JW, et al. \"Teriparatide and pelvic fracture healing: a phase 2 randomized controlled trial.\" Osteoporos Int, 2022;33(1):239-250. PMID: 34383100.", "pmid": "34383100" }, { "type": "pubmed", "citation": "Johansson T. \"PTH 1-34 (teriparatide) may not improve healing in proximal humerus fractures. A randomized, controlled study of 40 patients.\" Acta Orthop, 2016;87(1):79-82. PMID: 26179771.", "pmid": "26179771" }, { "type": "pubmed", "citation": "Neer RM, et al. \"Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis.\" N Engl J Med, 2001;344(19):1434-41. PMID: 11346808.", "pmid": "11346808" }, { "type": "fda-pi", "citation": "Forteo (teriparatide) injection Prescribing Information, sections 1 and 2 (DailyMed version 44, effective August 3, 2026; read September 30, 2026)." } ], "interactionCoverage": "partial", "related": [ "somatropin", "ghk-cu", "tb-500" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "terlipressin", "name": "Terlipressin", "aliases": [ "Terlivaz", "Glypressin", "Lucassin", "Variquel", "Remestyp", "Triglycyl lysine vasopressin" ], "tier": "mid", "category": "cardiovascular", "subcategory": "Long-acting V1a vasopressin receptor agonist (prodrug)", "class": "A synthetic dodecapeptide prodrug of lysine-vasopressin — three N-terminal glycyl residues are gradually cleaved by endothelial endopeptidases to release the active agent lysine-vasopressin — providing sustained V1a-selective vasoconstriction with an intermittent IV-bolus dosing profile suitable for ward-level care.", "tagline": "Terlivaz — the first and only FDA-approved drug for hepatorenal syndrome (HRS). FDA-approved September 2022 (Mallinckrodt) for adults with HRS with rapid reduction in kidney function, after a multi-decade regulatory history including four prior Complete Response Letters and the successful CONFIRM Phase 3 trial (NEJM 2021).", "oneLiner": "A synthetic triglycyl-lysine-vasopressin dodecapeptide prodrug developed in the 1960s by Ferring Pharmaceuticals and marketed outside the US for decades (Glypressin®, Lucassin®). The three N-terminal glycine residues act as a slow-release handle — endogenous endothelial endopeptidases cleave them sequentially to release lysine-vasopressin (lypressin) over approximately six hours per bolus dose, giving an intermittent-dosing alternative to continuous vasopressin infusion. Mallinckrodt's Terlivaz® received FDA approval on 14 September 2022 after priority review, fast-track designation, orphan designation, and four prior Complete Response Letters; approval was based on the CONFIRM Phase 3 trial (n=300, NEJM March 2021) showing improved Verified HRS Reversal (29.1% vs 15.8% placebo, p=0.012). Indication: improving kidney function in adults with HRS with rapid reduction in kidney function. Carries a boxed warning for serious / fatal respiratory failure.", "sequence": "Gly-Gly-Gly-Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Lys-Gly-NH2 (disulfide Cys4-Cys9)", "molecularFormula": "C52H74N16O15S2", "molecularWeight": 1227.37, "halfLife": { "value": null, "unit": null, "range": "the label gives no half-life; it reports steady-state exposure for terlipressin and its active metabolite lysine-vasopressin from 69 patients", "source": { "type": "label", "ref": "Terlivaz (terlipressin) prescribing information, boxed warning and sections 1, 2 and 12.3 (DailyMed SPL version 7, effective June 19, 2026; read October 1, 2026)" } }, "fdaStatus": "approved", "approvalDetails": "Terlivaz, NDA 022231, approved September 14, 2022, to improve kidney function in adults with hepatorenal syndrome with rapid reduction in kidney function; patients with serum creatinine above 5 mg/dL are unlikely to benefit. Boxed warning for serious or fatal respiratory failure (Drugs@FDA and the label, read October 1, 2026).", "mechanism": "Terlipressin itself has modest direct V1a receptor activity. The three N-terminal glycine residues are sequentially cleaved by endothelial endopeptidases to release lysine-vasopressin (lypressin) — a V1a-selective vasoconstrictor. V1a receptor activation in the splanchnic vasculature is the therapeutic mechanism in hepatorenal syndrome: splanchnic vasoconstriction reduces the pathologic splanchnic arterial vasodilation that underlies HRS, restoring effective arterial blood volume and renal perfusion. Selectivity for V1a over V2 is higher than for native vasopressin, reducing free-water-retention liability. The prodrug architecture allows intermittent IV bolus dosing (every 4–6 hours) rather than the continuous-infusion requirement of vasopressin itself.", "primaryUses": [ "Hepatorenal syndrome with rapid reduction in kidney function (FDA-approved)", "Bleeding esophageal varices (international approvals — portal-pressure reduction)", "Type 1 hepatorenal syndrome (international approvals — European guidelines)" ], "typicalDose": { "range": "0.85", "unit": "mg", "frequency": "every 6 hours", "route": "intravenous", "notes": "Terlivaz label: 0.85 mg (one vial) intravenously every six hours on days 1 to 3; on day 4 assess serum creatinine against baseline and continue only if it has fallen by at least 30%. Check oxygen saturation before the first dose and monitor continuously." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Terlivaz (terlipressin) prescribing information, boxed warning and sections 1, 2 and 12.3 (DailyMed SPL version 7, effective June 19, 2026; read October 1, 2026)." }, { "type": "pubmed", "citation": "Wong F, et al. \"Terlipressin plus Albumin for the Treatment of Type 1 Hepatorenal Syndrome.\" N Engl J Med, 2021;384(9):818-828. PMID: 33657294.", "pmid": "33657294" }, { "type": "pubmed", "citation": "Arora V, et al. \"Terlipressin Is Superior to Noradrenaline in the Management of Acute Kidney Injury in Acute on Chronic Liver Failure.\" Hepatology, 2020;71(2):600-610. PMID: 30076614.", "pmid": "30076614" }, { "type": "pubmed", "citation": "Cavallin M, et al. \"Terlipressin plus albumin versus midodrine and octreotide plus albumin in the treatment of hepatorenal syndrome: A randomized trial.\" Hepatology, 2015;62(2):567-74. PMID: 25644760.", "pmid": "25644760" }, { "type": "pubmed", "citation": "Tongyoo S, et al. \"Adjunctive terlipressin versus placebo in the treatment of refractory septic shock: a randomized, placebo-controlled trial.\" Crit Care, 2025;29(1):443. PMID: 41121365.", "pmid": "41121365" }, { "type": "pubmed", "citation": "Cavallin M, et al. \"Terlipressin given by continuous intravenous infusion versus intravenous boluses in the treatment of hepatorenal syndrome: A randomized controlled study.\" Hepatology, 2016;63(3):983-92. PMID: 26659927.", "pmid": "26659927" }, { "type": "news-release", "citation": "Mallinckrodt plc. \"Mallinckrodt Receives U.S. FDA Approval for Terlivaz® (terlipressin) for injection for the Treatment of Hepatorenal Syndrome (HRS).\" September 14, 2022." } ], "interactionCoverage": "studied", "related": [ "vasopressin", "desmopressin", "angiotensin-ii" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S5", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Not named. Terlipressin is a prodrug of lysine-vasopressin; S5 names the analogue desmopressin and covers substances with a similar biological effect, without saying whether that reaches terlipressin." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S5", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Not named. Terlipressin is a prodrug of lysine-vasopressin; S5 names the analogue desmopressin and covers substances with a similar biological effect, without saying whether that reaches terlipressin." } ], "moleculeClass": "peptide" }, { "id": "tesamorelin", "name": "Tesamorelin", "aliases": [ "Egrifta", "Egrifta SV", "TH9507" ], "tier": "full", "category": "growth-hormone", "subcategory": "GHRH analog", "class": "Stabilized synthetic analog of growth hormone-releasing hormone (GHRH).", "tagline": "An FDA-approved GHRH analog for reducing excess visceral fat in HIV-associated lipodystrophy.", "oneLiner": "A 44-amino-acid synthetic analogue of human GHRH with a trans-3-hexenoyl group added at the N-terminus, which stabilises it; it makes the pituitary release more of its own growth hormone.", "sequence": "YADAIFTNSYRKVLGQLSARKLLQDIMSRQQGESNQERGARARL (with N-terminal trans-3-hexenoyl group)", "molecularFormula": "C221H366N72O67S", "molecularWeight": 5135, "halfLife": { "value": null, "unit": null, "range": "8–11 minutes (current labels)", "notes": "Single subcutaneous dose in healthy subjects: 8 minutes for EGRIFTA SV 1.4 mg and 11 minutes for EGRIFTA WR 1.28 mg. The IGF-1 rise is what lasts: mean IGF-1 rose 108 ng/mL over 26 weeks in the phase 3 trials." }, "fdaStatus": "approved", "approvalDetails": "FDA-approved (initial US approval 2010) to reduce excess abdominal fat in HIV-infected adults with lipodystrophy; sold by Theratechnologies as EGRIFTA SV (1.4 mg daily) and EGRIFTA WR (1.28 mg daily, label revised March 2025). The EU application was withdrawn in June 2012; Canada's two EGRIFTA products are cancelled.", "mechanism": "Synthetic analogue of human GHRH(1-44) that binds pituitary GHRH receptors and raises basal and pulsatile release of the body's own growth hormone, and with it IGF-1. In trials it reduced visceral fat but not subcutaneous fat, and the loss reversed when treatment stopped. It needs an intact pituitary, and it can raise IGF-1 above the normal range and impair glucose tolerance.", "primaryUses": [ "Excess abdominal fat in HIV-associated lipodystrophy (FDA-approved)", "Fatty liver disease in people with HIV (trials; not an approved use)" ], "typicalDose": { "range": "1.28–2", "unit": "mg", "frequency": "once daily", "route": "subcutaneous", "notes": "Label doses by formulation: EGRIFTA WR 1.28 mg and EGRIFTA SV 1.4 mg once daily; the phase 3 trials used 2 mg of the original EGRIFTA, and the WR label cites comparable exposure. Injected under the skin of the abdomen." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "EGRIFTA WR (tesamorelin) for injection, Prescribing Information. Theratechnologies Inc. Revised March 2025; DailyMed, published August 3, 2026." }, { "type": "fda-pi", "citation": "EGRIFTA SV (tesamorelin) for injection, Prescribing Information. Theratechnologies Inc. DailyMed, published July 31, 2026." }, { "type": "clinical-trial", "citation": "Falutz J, et al. \"Effects of tesamorelin (TH9507), a growth hormone-releasing factor analog, in human immunodeficiency virus-infected patients with excess abdominal fat: a pooled analysis of two multicenter, double-blind placebo-controlled phase 3 trials with safety extension data.\" J Clin Endocrinol Metab, 2010;95(9):4291-304. PMID: 20554713.", "pmid": "20554713" }, { "type": "pubmed", "citation": "Falutz J, et al. \"Long-term safety and effects of tesamorelin, a growth hormone-releasing factor analogue, in HIV patients with abdominal fat accumulation.\" AIDS, 2008;22(14):1719-28. PMID: 18690162.", "pmid": "18690162" }, { "type": "clinical-trial", "citation": "Stanley TL, et al. \"Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation: a randomized clinical trial.\" JAMA, 2014;312(4):380-9. PMID: 25038357.", "pmid": "25038357" }, { "type": "clinical-trial", "citation": "Stanley TL, et al. \"Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial.\" Lancet HIV, 2019;6(12):e821-e830. PMID: 31611038.", "pmid": "31611038" }, { "type": "pubmed", "citation": "Fourman LT, et al. \"Effects of tesamorelin on hepatic transcriptomic signatures in HIV-associated NAFLD.\" JCI Insight, 2020;5(16). PMID: 32701508.", "pmid": "32701508" }, { "type": "pubmed", "citation": "Russo SC, et al. \"Efficacy and safety of tesamorelin in people with HIV on integrase inhibitors.\" AIDS, 2024;38(12):1758-1764. PMID: 38905488.", "pmid": "38905488" }, { "type": "pubmed", "citation": "Ellis RJ, et al. \"Effects of Tesamorelin on Neurocognitive Impairment in Persons With HIV and Abdominal Obesity.\" J Infect Dis, 2025;231(5):1230-1238. PMID: 39813152.", "pmid": "39813152" }, { "type": "pubmed", "citation": "Clemmons DR, et al. \"Safety and metabolic effects of tesamorelin, a growth hormone-releasing factor analogue, in patients with type 2 diabetes: A randomized, placebo-controlled trial.\" PLoS One, 2017;12(6):e0179538. PMID: 28617838.", "pmid": "28617838" }, { "type": "pubmed", "citation": "Adrian S, et al. \"The Growth Hormone Releasing Hormone Analogue, Tesamorelin, Decreases Muscle Fat and Increases Muscle Area in Adults with HIV.\" J Frailty Aging, 2019;8(3):154-159. PMID: 31237318.", "pmid": "31237318" }, { "type": "pubmed", "citation": "Lake JE, et al. \"Tesamorelin improves fat quality independent of changes in fat quantity.\" AIDS, 2021;35(9):1395-1402. PMID: 33756511.", "pmid": "33756511" }, { "type": "pubmed", "citation": "Fourman LT, et al. \"Visceral fat reduction with tesamorelin is associated with improved liver enzymes in HIV.\" AIDS, 2017;31(16):2253-2259. PMID: 28832410.", "pmid": "28832410" }, { "type": "pubmed", "citation": "Stanley TL, et al. \"Effects of tesamorelin on inflammatory markers in HIV patients with excess abdominal fat: relationship with visceral adipose reduction.\" AIDS, 2011;25(10):1281-8. PMID: 21516030.", "pmid": "21516030" }, { "type": "pubmed", "citation": "González-Sales M, et al. \"Population pharmacokinetic analysis of tesamorelin in HIV-infected patients and healthy subjects.\" Clin Pharmacokinet, 2015;54(3):285-94. PMID: 25358450.", "pmid": "25358450" }, { "type": "review", "citation": "Badran AS, et al. \"Body composition, hepatic fat, metabolic, and safety outcomes of Tesamorelin, a GHRH analogue, in HIV-associated lipodystrophy: A meta-analysis of randomized controlled trials.\" Obes Res Clin Pract, 2026;20(1):2-12. PMID: 41545261.", "pmid": "41545261" }, { "type": "review", "citation": "Dhillon S. \"Tesamorelin: a review of its use in the management of HIV-associated lipodystrophy.\" Drugs, 2011;71(8):1071-91. PMID: 21668043.", "pmid": "21668043" }, { "type": "other", "citation": "European Medicines Agency. Egrifta (tesamorelin): withdrawal of the marketing authorisation application, EMEA/H/C/002427, June 21, 2012." }, { "type": "other", "citation": "Theratechnologies Inc. Material change report: Ferrer Internacional withdraws the EU marketing authorisation application for tesamorelin, June 22, 2012." }, { "type": "other", "citation": "Health Canada Drug Product Database: EGRIFTA, drug codes 90838 and 92311 (Theratechnologies). Read September 26, 2026." } ], "interactionCoverage": "full", "related": [ "cjc-1295", "ipamorelin", "sermorelin" ], "lastReviewed": "2026-09-26", "publishedAt": "2026-04-18", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.2.4", "named": true, "wording": "tesamorelin", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "FDA-approved and WADA-prohibited at the same time: the two regimes are unrelated." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.2.4", "named": true, "wording": "tesamorelin", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "FDA-approved and WADA-prohibited at the same time: the two regimes are unrelated." } ], "moleculeClass": "peptide" }, { "id": "tesofensine", "name": "Tesofensine", "aliases": [ "NS2330" ], "tier": "full", "category": "research", "subcategory": "monoamine reuptake inhibitor (anti-obesity)", "class": "A small-molecule serotonin–norepinephrine–dopamine triple reuptake inhibitor originally developed for Alzheimer's and Parkinson's disease, repurposed as an anti-obesity agent.", "tagline": "A triple monoamine reuptake inhibitor, not a peptide: 9 to 11% more weight loss than placebo at 24 weeks in phase 2, a faster heart rate, a ten-day half-life, and no approval anywhere.", "oneLiner": "A small-molecule dopamine, noradrenaline and serotonin reuptake inhibitor (NS2330) developed for Alzheimer's and Parkinson's disease, repurposed for obesity after trial participants lost weight.", "sequence": null, "molecularFormula": "C17H23Cl2NO", "molecularWeight": 328.3, "halfLife": { "value": 234, "unit": "hours", "range": "234 h (tesofensine); 374 h (active metabolite M1)", "notes": "Population pharmacokinetic model from 320 patients in a 14-week Alzheimer's trial (2007); enterohepatic recirculation prolongs it further. Detectable in urine for up to 500 h after a single small dose (2026)." }, "fdaStatus": "clinical-trials", "approvalDetails": "Not approved anywhere. Medix's Mexican application (phase 3, 372 patients) received a favourable COFEPRIS committee opinion in 2023, was not approved on November 6, 2024, and was resubmitted on February 20, 2025; no approval had been announced as of September 27, 2026. The earlier statement that a tesofensine-metoprolol product (Tesomet) was approved in Mexico in 2023 was wrong: Tesomet is a separate candidate for rare eating disorders.", "mechanism": "Blocks the presynaptic reuptake of serotonin, noradrenaline, and dopamine, producing central appetite suppression and increased resting metabolic rate analogous to stimulant-class anorectics but with a longer duration of action than classical agents like phentermine. The monoaminergic mechanism drives the cardiovascular side-effect profile — elevations in heart rate and blood pressure are the primary tolerability and safety limitation.", "primaryUses": [ "Research into obesity pharmacotherapy", "Historical research in Alzheimer's and Parkinson's disease (deprioritized)" ], "typicalDose": { "range": "0.25–1.0", "unit": "mg", "frequency": "daily", "route": "oral", "notes": "Phase 2 obesity trials used 0.25, 0.5, and 1.0 mg/day for 24 weeks. Not a community research-chemical target — sold online as a research reference compound only." }, "evidenceLevel": "medium", "sources": [ { "type": "Human", "citation": "Lehr T, et al. \"Population pharmacokinetic modelling of NS2330 (tesofensine) and its major metabolite in patients with Alzheimer's disease.\" Br J Clin Pharmacol, 2007;64(1):36-48. PMID: 17324246.", "pmid": "17324246" }, { "type": "Human", "citation": "Hauser RA, et al. \"Randomized trial of the triple monoamine reuptake inhibitor NS 2330 (tesofensine) in early Parkinson's disease.\" Mov Disord, 2007;22(3):359-65. PMID: 17149725.", "pmid": "17149725" }, { "type": "Animal", "citation": "Larsen MH, et al. \"Expression of brain derived neurotrophic factor, activity-regulated cytoskeleton protein mRNA, and enhancement of adult hippocampal neurogenesis in rats after sub-chronic and chronic treatment with the triple monoamine re-uptake inhibitor tesofensine.\" Eur J Pharmacol, 2007;555(2-3):115-21. PMID: 17112503.", "pmid": "17112503" }, { "type": "Human", "citation": "Rascol O, et al. \"Tesofensine (NS 2330), a monoamine reuptake inhibitor, in patients with advanced Parkinson disease and motor fluctuations: the ADVANS Study.\" Arch Neurol, 2008;65(5):577-83. PMID: 18474731.", "pmid": "18474731" }, { "type": "Review", "citation": "Astrup A, et al. \"Weight loss produced by tesofensine in patients with Parkinson's or Alzheimer's disease.\" Obesity (Silver Spring), 2008;16(6):1363-9. PMID: 18356831.", "pmid": "18356831" }, { "type": "Animal", "citation": "Lehr T, et al. \"Contribution of the active metabolite M1 to the pharmacological activity of tesofensine in vivo: a pharmacokinetic-pharmacodynamic modelling approach.\" Br J Pharmacol, 2008;153(1):164-74. PMID: 17982477.", "pmid": "17982477" }, { "type": "Human", "citation": "Astrup A, et al. \"Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial.\" Lancet, 2008;372(9653):1906-1913. PMID: 18950853.", "pmid": "18950853" }, { "type": "Human", "citation": "Lehr T, et al. \"A quantitative enterohepatic circulation model: development and evaluation with tesofensine and meloxicam.\" Clin Pharmacokinet, 2009;48(8):529-42. PMID: 19705923.", "pmid": "19705923" }, { "type": "Human", "citation": "Sjödin A, et al. \"The effect of the triple monoamine reuptake inhibitor tesofensine on energy metabolism and appetite in overweight and moderately obese men.\" Int J Obes (Lond), 2010;34(11):1634-43. PMID: 20479765.", "pmid": "20479765" }, { "type": "Human", "citation": "Schoedel KA, et al. \"Subjective and objective effects of the novel triple reuptake inhibitor tesofensine in recreational stimulant users.\" Clin Pharmacol Ther, 2010;88(1):69-78. PMID: 20520602.", "pmid": "20520602" }, { "type": "Animal", "citation": "Axel AM, et al. \"Tesofensine, a novel triple monoamine reuptake inhibitor, induces appetite suppression by indirect stimulation of alpha1 adrenoceptor and dopamine D1 receptor pathways in the diet-induced obese rat.\" Neuropsychopharmacology, 2010;35(7):1464-76. PMID: 20200509.", "pmid": "20200509" }, { "type": "Animal", "citation": "Hansen HH, et al. \"The novel triple monoamine reuptake inhibitor tesofensine induces sustained weight loss and improves glycemic control in the diet-induced obese rat: comparison to sibutramine and rimonabant.\" Eur J Pharmacol, 2010;636(1-3):88-95. PMID: 20385125.", "pmid": "20385125" }, { "type": "Human", "citation": "Gilbert JA, et al. \"The effect of tesofensine on appetite sensations.\" Obesity (Silver Spring), 2012;20(3):553-61. PMID: 21720440.", "pmid": "21720440" }, { "type": "Animal", "citation": "van de Giessen E, et al. \"Triple monoamine inhibitor tesofensine decreases food intake, body weight, and striatal dopamine D2/D3 receptor availability in diet-induced obese rats.\" Eur Neuropsychopharmacol, 2012;22(4):290-9. PMID: 21889317.", "pmid": "21889317" }, { "type": "Animal", "citation": "Bentzen BH, et al. \"Anti-hypertensive treatment preserves appetite suppression while preventing cardiovascular adverse effects of tesofensine in rats.\" Obesity (Silver Spring), 2013;21(5):985-92. PMID: 23784901.", "pmid": "23784901" }, { "type": "Animal", "citation": "Hansen HH, et al. \"Tesofensine induces appetite suppression and weight loss with reversal of low forebrain dopamine levels in the diet-induced obese rat.\" Pharmacol Biochem Behav, 2013;110:265-71. PMID: 23932919.", "pmid": "23932919" }, { "type": "Animal", "citation": "Perez CI, et al. \"Tesofensine, a novel antiobesity drug, silences GABAergic hypothalamic neurons.\" PLoS One, 2024;19(4):e0300544. PMID: 38656972.", "pmid": "38656972" }, { "type": "Human", "citation": "Krug O, et al. \"Investigations Into the Metabolism and Elimination of Tesofensine in Human Urine.\" Drug Test Anal, 2026;18(9):1163-1173. PMID: 42320973.", "pmid": "42320973" } ], "interactionCoverage": "studied", "related": [ "adipotide", "semaglutide", "tirzepatide" ], "lastReviewed": "2026-09-27", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": "", "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited-in-competition", "section": "S6.B", "named": true, "wording": "Tesofensine", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited-in-competition", "section": "S6.B", "named": true, "wording": "Tesofensine", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "small-molecule", "moleculeClassBasis": "small-molecule" }, { "id": "testagen", "name": "Testagen", "aliases": [ "Testis peptide bioregulator", "KEDG tetrapeptide (Khavinson testis)" ], "tier": "stub", "category": "longevity", "subcategory": "Khavinson testis-derived peptide bioregulator", "class": "A testis-tissue-derived short peptide bioregulator in the Khavinson framework, with overlapping nomenclature to Ventfort in some Khavinson publications (both have been associated with the synthetic KEDG tetrapeptide).", "tagline": "A Khavinson testis bioregulator preparation — note that the synthetic tetrapeptide KEDG has been reported in different Khavinson-group publications under both the Testagen and Ventfort names, reflecting either genuine tissue-source overlap or inconsistent nomenclature in the primary literature. Evidence is Russian-language; Russian nutraceutical status only.", "oneLiner": "A testis-tissue-derived short peptide bioregulator in the Khavinson cytomedine series. The synthetic tetrapeptide Lys-Glu-Asp-Gly (KEDG) has been associated with Testagen in some Khavinson publications and with Ventfort (vascular) in others; this reflects either a shared active fragment across bioregulator preparations or inconsistent naming in the primary Khavinson literature. The encyclopedia treats Testagen and Ventfort as separate entries because they are marketed separately with different primary indications, but users should be aware that the underlying synthetic peptide is reported to be the same.", "sequence": "Lys-Glu-Asp-Gly (KEDG, reported synthetic active fragment — shared with Ventfort in some publications)", "molecularFormula": "C17H30N6O8", "molecularWeight": 446.46, "halfLife": { "value": null, "unit": null, "range": "Not characterized in humans", "notes": "No peer-reviewed Western pharmacokinetic data." }, "fdaStatus": "not-approved-us", "approvalDetails": "Not FDA- or EMA-approved. Russian nutraceutical status only.", "mechanism": "Proposed to support testis-axis aging and male reproductive decline under the Khavinson-framework tissue-specific gene-expression hypothesis. Molecular validation minimal.", "primaryUses": [ "Testis-axis aging support (Russian nutraceutical positioning)", "Male reproductive aging adjunct (anecdotal / Russian clinical use)" ], "typicalDose": { "range": "1–2 capsules", "unit": null, "frequency": "1–2 times daily in 20–30 day courses", "route": "oral", "notes": "Russian nutraceutical dosing. No controlled efficacy evidence." }, "evidenceLevel": "low", "sources": [ { "type": "review", "citation": "Khavinson VK, et al. \"Peptide bioregulation of endocrine function and aging.\" Adv Gerontol, 2012;25:11-23 (Russian)." }, { "type": "review", "citation": "Anisimov VN, Khavinson VK. \"Peptide bioregulation of aging: results and prospects.\" Biogerontology, 2010;11:139-149. PMID: 19830585.", "pmid": "19830585" } ], "interactionCoverage": "none-found", "related": [ "ventfort", "prostamax", "epithalon" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": "", "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "thymalin", "name": "Thymalin", "aliases": [ "Timalin", "Thymus peptide complex", "Calf-thymus polypeptide preparation" ], "tier": "mid", "category": "longevity", "subcategory": "Calf-thymus polypeptide complex (Khavinson immune-longevity)", "class": "A polypeptide complex extracted from calf thymus, historically marketed in Russia as an immune-supportive therapy and positioned in the Khavinson framework as a thymic-aging bioregulator.", "tagline": "A polypeptide mixture extracted from calf thymus, injected as an immune modulator and approved in Russia. Its human studies are small, mostly Russian and usually add it to other treatment; in a non-randomised COVID-19 comparison, hospital mortality was 20.6% with thymalin against 40.9% on standard care. Not approved in the US.", "oneLiner": "A polypeptide complex extracted from calf thymus, given by intramuscular injection in courses and approved in Russia as an immune modulator. Not a single molecule, so it has no formula or measured half-life; its published evidence is small Russian studies, mostly as an add-on.", "sequence": "Polypeptide mixture — not a single-sequence molecule", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": null, "range": "Not established", "notes": "Thymalin is an extract rather than a single molecule, so no half-life has been measured for the mixture.", "source": { "type": "qualitative", "note": "a description with no figure; no half-life measurement is cited for it" } }, "fdaStatus": "not-approved-us", "approvalDetails": "Approved in Russia; not approved in the US, where Drugs@FDA holds no application (openFDA, read September 30, 2026).", "mechanism": "Proposed to provide thymic-tissue-specific short peptides that support thymic-axis function in aging, including T-lymphocyte maturation, CD4/CD8 balance, and IL-2 production. The characterized synthetic dipeptide isolated from thymic bioregulator preparations is Glu-Trp (thymogen); several other short peptides have been reported. Mechanism at the molecular level is partially characterized but the clinical validation rests primarily on Russian-language cohort and immune-biomarker studies.", "primaryUses": [ "Immune modulation (approved in Russia)", "Add-on treatment in small Russian clinical studies", "Immune and thymus research" ], "typicalDose": { "range": "5–20", "unit": "mg", "frequency": "once daily for 5–10 days in courses", "route": "intramuscular", "notes": "Standard Russian dosing: 5–20 mg IM once daily for 5–10 days, repeated every 3–6 months. Thymalin lyophilizate reconstituted in 1–2 mL sterile saline." }, "evidenceLevel": "low", "sources": [ { "type": "fda", "citation": "FDA. Drugs@FDA (openFDA): no application for thymalin. Read September 30, 2026." }, { "type": "pubmed", "citation": "Kuznik BI, et al. \"[Morphological compound and indicators of the blood clotting system in severe COVID-19 patients of middle aged and elderly during treatment of Tocilizumab and Thymalin.].\" Adv Gerontol, 2022;35(3):368-374. PMID: 36169363.", "pmid": "36169363" }, { "type": "pubmed", "citation": "Khavinson VK, et al. \"Thymalin: Activation of Differentiation of Human Hematopoietic Stem Cells.\" Bull Exp Biol Med, 2020;170(1):118-122. PMID: 33237528.", "pmid": "33237528" }, { "type": "pubmed", "citation": "Musienko GV. \"[Thymalin in the combined treatment of parkinsonism patients].\" Lik Sprava, 1999:119-22. PMID: 10424021.", "pmid": "10424021" }, { "type": "pubmed", "citation": "Govorin NV, et al. \"[Use of thymic peptide thymalin in the complex treatment of therapy-resistant schizophrenia].\" Zh Nevropatol Psikhiatr Im S S Korsakova, 1990;90(3):100-3. PMID: 2163147.", "pmid": "2163147" }, { "type": "pubmed", "citation": "Zhukova GV, et al. \"Effect of Thymalin on the Tumor and Thymus under Conditions of Activation Therapy In Vivo.\" Bull Exp Biol Med, 2018;165(1):80-83. PMID: 29797130.", "pmid": "29797130" }, { "type": "pubmed", "citation": "Boiko AA, et al. \"Reparative osteogenesis in mandible in cases of filling a bone defect with hydroxyapatite-containing osteotropic material and injecting the surrounding soft tissues with thymalin: experimental and morphological study.\" Wiad Lek, 2024;77(1):68-76. PMID: 38431810.", "pmid": "38431810" }, { "type": "other", "citation": "Тималин® (Thymalin) instructions for medical use, Samson-Med, Russia: thymus extract 10 mg for intramuscular injection; prescription-only per RLS. Read September 30, 2026." } ], "interactionCoverage": "none-found", "related": [ "thymogen", "thymulin", "thymopentin" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": "Russia", "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "blend", "moleculeClassBasis": "polypeptide complex" }, { "id": "thymogen", "name": "Thymogen", "aliases": [ "Timogen", "Glutamyl-tryptophan", "Glu-Trp dipeptide" ], "tier": "mid", "category": "longevity", "subcategory": "Synthetic thymus-derived dipeptide (Khavinson)", "class": "A synthetic dipeptide (Glu-Trp) isolated from thymic bioregulator preparations and registered in Russia as a medicine; positioned in the Khavinson framework as the characterized active fragment of Thymalin.", "tagline": "L-glutamyl-L-tryptophan, a synthetic dipeptide developed in the Soviet Union and used in Russia as an immunomodulator; its evidence is small, mostly uncontrolled Russian-language studies and one double-blind surgical trial. No FDA or EMA approval.", "oneLiner": "A synthetic dipeptide consisting of glutamic acid and tryptophan (Glu-Trp), isolated and characterized by Khavinson's group as the smallest active fragment of the calf-thymus polypeptide bioregulator preparation that gave rise to Thymalin. Registered in Russia as a medicine for immune-deficiency states and used as a shorter-course alternative to Thymalin. Not FDA- or EMA-approved. Mechanism of action proposed to involve IL-2 receptor expression modulation on T lymphocytes and T-helper cell maturation, with supportive data primarily from Russian-language immune-biomarker studies.", "sequence": "Glu-Trp", "molecularFormula": "C16H19N3O5", "molecularWeight": 333.34, "halfLife": { "value": null, "unit": null, "range": "Not reported in the abstracts read", "notes": "The earlier 'short plasma half-life consistent with dipeptide pharmacokinetics' had no source.", "source": { "type": "qualitative", "note": "a description with no figure; no half-life measurement is cited for it" } }, "fdaStatus": "not-approved-us", "approvalDetails": "Developed in the Soviet Union and used in Russia as an immunomodulating drug (described as a new domestic drug in a 1992 clinical report, PMID 1476231). Not FDA-approved and not in EMA's register (both read September 30, 2026).", "mechanism": "Proposed to upregulate IL-2 receptor expression on T lymphocytes and to support T-helper cell maturation. Khavinson-group publications report gene-expression-modulatory effects in thymic tissue cultures and in vivo in aged rodent models. Molecular characterization is partial; clinical validation rests primarily on Russian-language studies.", "primaryUses": [ "Immune-deficiency states (Russian approval)", "Acute respiratory infection prophylaxis (Russian nasal-spray approval)", "Thymic-axis aging support (Khavinson positioning)" ], "typicalDose": { "range": null, "unit": null, "frequency": "courses of daily doses (Russian studies)", "route": "injection or intranasal", "notes": "Russian product labelling was not read; the studies used courses of injections or intranasal doses." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Smirnov VS, et al. \"[Application thymogen for preoperative preparation of elderly patients with tumor processes in abdominal cavity].\" Adv Gerontol, 2011;24(2):278-84. PMID: 21957588.", "pmid": "21957588" }, { "type": "pubmed", "citation": "Tsvelev IuV, et al. \"[Thymogen in the complex treatment of inflammatory diseases of the female genital system].\" Akush Ginekol (Mosk), 1992:54-7. PMID: 1476231.", "pmid": "1476231" }, { "type": "pubmed", "citation": "Zhuk EA, et al. \"[Thymogen in the treatment of type-1 diabetes mellitus].\" Ter Arkh, 1996;68(10):12-4. PMID: 9026934.", "pmid": "9026934" }, { "type": "pubmed", "citation": "Medus AI, et al. \"[The effect of thymogen on the state of immunity in destructive pulmonary tuberculosis].\" Voen Med Zh, 1999;320(10):65-7, 96. PMID: 10605346.", "pmid": "10605346" }, { "type": "pubmed", "citation": "Furgal SM, et al. \"[The clinico-epidemiological efficacy of thymogen in acute respiratory viral infections in a military collective].\" Voen Med Zh, 1993:31-2, 80. PMID: 8498021.", "pmid": "8498021" }, { "type": "pubmed", "citation": "Anisimov VN, et al. \"[The effect of the synthetic immunomodulator thymogen on radiation-induced carcinogenesis in rats].\" Vopr Onkol, 1992;38(4):451-8. PMID: 1300740.", "pmid": "1300740" }, { "type": "pubmed", "citation": "Deigin V, et al. \"The First Reciprocal Activities of Chiral Peptide Pharmaceuticals: Thymogen and Thymodepressin, as Examples.\" Int J Mol Sci, 2024;25(9). PMID: 38732260.", "pmid": "38732260" }, { "type": "fda", "citation": "FDA. Drugs@FDA (openFDA): no application for thymogen. Read September 30, 2026." }, { "type": "other", "citation": "European Medicines Agency. Medicines register: no entry for thymogen. Read September 30, 2026." } ], "interactionCoverage": "none-found", "related": [ "thymalin", "thymulin", "thymopentin" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": "Russia", "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "thymopentin", "name": "Thymopentin", "aliases": [ "TP-5", "TP5", "Timunox", "Thymopoietin 32-36" ], "tier": "mid", "category": "immune", "subcategory": "thymic pentapeptide", "class": "A synthetic pentapeptide corresponding to the active site (residues 32–36) of thymopoietin.", "tagline": "A synthetic five-amino-acid fragment of thymopoietin (TP-5), sold as Timunox. Small 1980s and 1990s trials found modest benefits over placebo in atopic dermatitis and rheumatoid arthritis. Not approved in the US.", "oneLiner": "A synthetic pentapeptide (Arg-Lys-Asp-Val-Tyr), residues 32 to 36 of the thymic hormone thymopoietin, studied as an immune modulator and sold as Timunox. Small 1980s and 1990s trials found modest benefits in atopic dermatitis and rheumatoid arthritis.", "sequence": "Arg-Lys-Asp-Val-Tyr", "molecularFormula": "C30H49N9O9", "molecularWeight": 679.77, "halfLife": { "value": null, "unit": null, "range": "extremely short in the body; not measured in people in the sources read", "source": { "type": "pmid", "pmid": "30002492", "cite": "Zhang T, et al. \"Thymopentin-loaded phospholipid-based phase separation gel with long-lasting immunomodulatory effects: in vitro and in vivo studies.\" Acta Pharmacol Sin, 2019;40(4):514-521. PMID: 30002492." } }, "fdaStatus": "not-approved-us", "approvalDetails": "Not approved in the US; Drugs@FDA holds no application (openFDA, read September 30, 2026). Studied as Timunox.", "mechanism": "Induces T-cell differentiation from immature precursors, modulates T-helper and T-suppressor activity, and enhances NK cell cytotoxicity. Despite ultra-short plasma half-life, signaling effects on T-cell lineage commitment persist for days. Used primarily in secondary immunodeficiency states.", "primaryUses": [ "Atopic dermatitis (1990s trials)", "Rheumatoid arthritis (1980s trials)", "Immune conditions (small studies)" ], "typicalDose": { "range": "50", "unit": "mg", "frequency": "3 times weekly", "route": "subcutaneous", "notes": "European clinical dosing: 50 mg SC three times weekly." }, "evidenceLevel": "medium", "sources": [ { "type": "fda", "citation": "FDA. Drugs@FDA (openFDA): no application for thymopentin. Read September 30, 2026." }, { "type": "pubmed", "citation": "Leung DY, et al. \"Thymopentin therapy reduces the clinical severity of atopic dermatitis.\" J Allergy Clin Immunol, 1990;85(5):927-33. PMID: 2185294.", "pmid": "2185294" }, { "type": "pubmed", "citation": "Stiller MJ, et al. \"A double-blind, placebo-controlled clinical trial to evaluate the safety and efficacy of thymopentin as an adjunctive treatment in atopic dermatitis.\" J Am Acad Dermatol, 1994;30(4):597-602. PMID: 8157786.", "pmid": "8157786" }, { "type": "pubmed", "citation": "Malaise MG, et al. \"Treatment of active rheumatoid arthritis with slow intravenous injections of thymopentin. A double-blind placebo-controlled randomised study.\" Lancet, 1985;1(8433):832-6. PMID: 2858708.", "pmid": "2858708" }, { "type": "pubmed", "citation": "Friedmann N. \"Thymopentin: safety overview.\" Surv Immunol Res, 1985;4 Suppl 1:139-48. PMID: 3898287.", "pmid": "3898287" }, { "type": "pubmed", "citation": "Goldstein G, et al. \"A synthetic pentapeptide with biological activity characteristic of the thymic hormone thymopoietin.\" Science, 1979;204(4399):1309-10. PMID: 451537.", "pmid": "451537" }, { "type": "pubmed", "citation": "Zhang T, et al. \"Thymopentin-loaded phospholipid-based phase separation gel with long-lasting immunomodulatory effects: in vitro and in vivo studies.\" Acta Pharmacol Sin, 2019;40(4):514-521. PMID: 30002492.", "pmid": "30002492" } ], "interactionCoverage": "studied", "related": [ "thymosin-alpha-1", "thymulin", "thymosin-beta-4" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": "some countries outside the US", "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "thymosin-alpha-1", "name": "Thymosin α1", "aliases": [ "Tα1", "thymalfasin", "Zadaxin", "TA1" ], "tier": "full", "category": "immune", "subcategory": "thymic immunomodulatory peptide", "class": "A 28-amino-acid N-acetylated thymic peptide, the N-terminal cleavage product of prothymosin alpha.", "tagline": "A thymic peptide approved as Zadaxin in about 35 countries; its hepatitis trials were mixed, and its largest trial, in 1,106 sepsis patients, found no effect on death.", "oneLiner": "A 28-amino-acid N-acetylated peptide first isolated from thymic tissue by Allan Goldstein in 1977, identical to the N-terminal fragment of prothymosin alpha, approved in over 35 countries under the brand name Zadaxin for chronic hepatitis B and C and as an immune enhancer.", "sequence": "Ac-Ser-Asp-Ala-Ala-Val-Asp-Thr-Ser-Ser-Glu-Ile-Thr-Thr-Lys-Asp-Leu-Lys-Glu-Lys-Lys-Glu-Val-Val-Glu-Glu-Ala-Glu-Asn-OH", "molecularFormula": "C129H215N33O55", "molecularWeight": 3108.3, "halfLife": { "value": 2, "unit": "hours", "range": "about 2 hours (serum, after injection under the skin)", "notes": "From a 2001 drug review (Ancell 2001): peak serum levels within 2 hours of a subcutaneous dose, back to baseline within 24 hours, serum half-life about 2 hours. The hepatitis trials gave 1.6 mg twice a week." }, "fdaStatus": "not-approved-us", "approvalDetails": "Approved in 35+ countries (including Italy, China, and much of Asia) as Zadaxin / thymalfasin for chronic hepatitis B, chronic hepatitis C, and as an immune enhancer. FDA orphan drug designations for malignant melanoma, chronic active hepatitis B, DiGeorge anomaly with immune defects, and hepatocellular carcinoma — but not FDA-approved for marketing. Manufactured by SciClone Pharmaceuticals.", "mechanism": "Modulates both innate and adaptive immunity. Activates TLR2 and TLR9 on dendritic cells and monocytes, driving NF-κB activation and production of IL-12, TNF-α, and IL-6. Promotes dendritic cell maturation, T-cell differentiation (particularly Th1), and enhances NK cell cytotoxicity. Restores immune function in immunocompromised states (hepatitis B/C, sepsis, post-chemotherapy) and enhances vaccine responses in elderly and hemodialysis populations.", "primaryUses": [ "Chronic hepatitis B and C (Zadaxin-approved)", "Immune enhancement in immunocompromised patients", "Sepsis (investigational)", "Severe COVID-19 (investigational)", "Vaccine adjuvant research", "Community off-label immune support" ], "typicalDose": { "range": "1.6", "unit": "mg", "frequency": "twice weekly", "route": "subcutaneous", "notes": "Standard Zadaxin dose: 1.6 mg (900 µg/m²) subcutaneously twice weekly for 6–12 months. Community dosing often mirrors this." }, "evidenceLevel": "high", "sources": [ { "type": "clinical-trial", "citation": "Wu J, et al. \"The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial.\" BMJ, 2025;388:e082583. PMID: 39814420.", "pmid": "39814420" }, { "type": "clinical-trial", "citation": "Chien RN, et al. \"Efficacy of thymosin alpha1 in patients with chronic hepatitis B: a randomized, controlled trial.\" Hepatology, 1998;27(5):1383-7. PMID: 9581695.", "pmid": "9581695" }, { "type": "pubmed", "citation": "Lim SG, et al. \"A randomized, placebo-controlled trial of thymosin-alpha1 and lymphoblastoid interferon for HBeAg-positive chronic hepatitis B.\" Antivir Ther, 2006;11(2):245-53. PMID: 16640105.", "pmid": "16640105" }, { "type": "pubmed", "citation": "Sherman KE, et al. \"Combination therapy with thymosin alpha1 and interferon for the treatment of chronic hepatitis C infection: a randomized, placebo-controlled double-blind trial.\" Hepatology, 1998;27(4):1128-35. PMID: 9537454.", "pmid": "9537454" }, { "type": "pubmed", "citation": "Shehadeh F, et al. \"A Pilot Trial of Thymalfasin (Thymosin-α-1) to Treat Hospitalized Patients With Hypoxemia and Lymphocytopenia Due to Coronavirus Disease 2019 Infection.\" J Infect Dis, 2023;227(2):226-235. PMID: 36056913.", "pmid": "36056913" }, { "type": "pubmed", "citation": "Wang Z, et al. \"Thymosin Alpha-1 Has no Beneficial Effect on Restoring CD4+ and CD8+ T Lymphocyte Counts in COVID-19 Patients.\" Front Immunol, 2021;12:568789. PMID: 34149679.", "pmid": "34149679" }, { "type": "pubmed", "citation": "Carraro G, et al. \"Thymosin-alpha 1 (Zadaxin) enhances the immunogenicity of an adjuvated pandemic H1N1v influenza vaccine (Focetria) in hemodialyzed patients: a pilot study.\" Vaccine, 2012;30(6):1170-80. PMID: 22178096.", "pmid": "22178096" }, { "type": "pubmed", "citation": "Chen C, et al. \"Role of thymosin α1 in restoring immune response in immunological nonresponders living with HIV.\" BMC Infect Dis, 2024;24(1):97. PMID: 38233816.", "pmid": "38233816" }, { "type": "pubmed", "citation": "Lopez M, et al. \"Biochemotherapy with thymosin alpha 1, interleukin-2 and dacarbazine in patients with metastatic melanoma: clinical and immunological effects.\" Ann Oncol, 1994;5(8):741-6. PMID: 7826907.", "pmid": "7826907" }, { "type": "pubmed", "citation": "Xu H, et al. \"Neoadjuvant immunochemotherapy plus thymalfasin in locally advanced gastric cancer: a prospective clinical trial.\" BMC Med, 2026;24(1). PMID: 41749205.", "pmid": "41749205" }, { "type": "review", "citation": "Yu Y, et al. \"[Evaluation of efficacy of thymosin alpha1 in the treatment of sepsis: a systematic review].\" Zhongguo Wei Zhong Bing Ji Jiu Yi Xue, 2009;21(1):21-4. PMID: 19141185.", "pmid": "19141185" }, { "type": "review", "citation": "Soeroto AY, et al. \"The efficacy of thymosin alpha-1 therapy in moderate to critical COVID-19 patients: a systematic review, meta-analysis, and meta-regression.\" Inflammopharmacology, 2023;31(6):3317-3325. PMID: 37845598.", "pmid": "37845598" }, { "type": "review", "citation": "Pica F, et al. \"Serum thymosin alpha 1 levels in normal and pathological conditions.\" Expert Opin Biol Ther, 2018;18(sup1):13-21. PMID: 30063864.", "pmid": "30063864" }, { "type": "review", "citation": "Dominari A, et al. \"Thymosin alpha 1: A comprehensive review of the literature.\" World J Virol, 2020;9(5):67-78. PMID: 33362999.", "pmid": "33362999" }, { "type": "pubmed", "citation": "Cheng Y, et al. \"Identification and determination of structurally related peptide impurities in thymalfasin by liquid chromatography-high-resolution mass spectrometry.\" Anal Bioanal Chem, 2022;414(28):8035-8045. PMID: 36207535.", "pmid": "36207535" }, { "type": "fda-pi", "citation": "Zadaxin (thymalfasin) Prescribing Information. SciClone Pharmaceuticals. (Approved in 35+ countries; not FDA.)" }, { "type": "pubmed", "citation": "Garaci E, et al. \"Thymosin alpha(1) in combination with cytokines and chemotherapy for the treatment of cancer.\" Int Immunopharmacol, 2003;3(8):1145-50. PMID: 12860169.", "pmid": "12860169" } ], "interactionCoverage": "partial", "related": [ "thymulin", "thymopentin", "thymosin-beta-4" ], "lastReviewed": "2026-09-26", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": "~35 countries, not the US", "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "thymosin-beta-4", "name": "Thymosin β4", "aliases": [ "Tβ4", "TB4", "TMSB4X", "RGN-259" ], "tier": "full", "category": "healing", "subcategory": "actin-binding regenerative peptide", "class": "A naturally occurring 43-amino-acid regenerative peptide, the parent molecule of the TB-500 fragment.", "tagline": "The body's main actin-sequestering peptide, 43 amino acids long: tested as eye drops (RGN-259) for dry eye and corneal wounds, and not the short TB-500 fragment.", "oneLiner": "A highly conserved 43-amino-acid, N-acetylated actin-sequestering peptide abundant in platelets, distinct from the short TB-500 fragment sold in the peptide market.", "sequence": "SDKPDMAEIEKFDKSKLKKTETQEKNPLPSKETIEQEKQAGES", "molecularFormula": "C212H350N56O78S", "molecularWeight": 4963.5, "halfLife": { "value": null, "unit": null, "range": "not reported in the abstracts we hold", "notes": "A 2010 intravenous safety study (42-1,260 mg/day) found the half-life lengthened as the dose rose; the figure is not in its abstract. The '~1 hour' given here before had no source." }, "fdaStatus": "clinical-trials", "approvalDetails": "Not approved anywhere. ReGenTree's 0.1% eye drops (RGN-259) completed phase 3 dry-eye trials in 2018 and 2021 (NCT02974907, NCT03937882); a phase 3 trial in neurotrophic keratopathy was terminated in 2020 (NCT02600429) and another was recruiting (NCT05555589; ClinicalTrials.gov, read September 27, 2026).", "mechanism": "Binds G-actin and sequesters monomeric actin, regulating cytoskeletal dynamics. Effects include promotion of endothelial cell migration (angiogenesis), modulation of inflammation via downregulation of NF-κB signaling, inhibition of myofibroblast transition (anti-scarring), and activation of progenitor cell populations. The actin-binding motif LKKTETQ within Tβ4 is the active core shared with the TB-500 fragment.", "primaryUses": [ "Dry eye disease (Phase 3)", "Neurotrophic keratopathy (clinical trials)", "Corneal wound healing", "Dermal wound healing research", "Post-MI cardiac repair (preclinical)" ], "typicalDose": { "range": "varies", "unit": "", "frequency": "varies by formulation", "route": "ophthalmic (RGN-259 eye drops, investigational); systemic research only", "notes": "No approved systemic dosing. Research injectable doses in the community overlap with TB-500 dosing despite being a longer peptide." }, "evidenceLevel": "medium", "sources": [ { "type": "Animal", "citation": "Girardi M, et al. \"Anti-inflammatory effects in the skin of thymosin-beta4 splice-variants.\" Immunology, 2003;109(1):1-7. PMID: 12709011.", "pmid": "12709011" }, { "type": "Review", "citation": "Goldstein AL, et al. \"Thymosin beta4: actin-sequestering protein moonlights to repair injured tissues.\" Trends Mol Med, 2005;11(9):421-9. PMID: 16099219.", "pmid": "16099219" }, { "type": "Animal", "citation": "Smart N, et al. \"Thymosin beta4 induces adult epicardial progenitor mobilization and neovascularization.\" Nature, 2007;445(7124):177-82. PMID: 17108969.", "pmid": "17108969" }, { "type": "Review", "citation": "Crockford D, et al. \"Thymosin beta4: structure, function, and biological properties supporting current and future clinical applications.\" Ann N Y Acad Sci, 2010;1194:179-89. PMID: 20536467.", "pmid": "20536467" }, { "type": "Human", "citation": "Ruff D, et al. \"A randomized, placebo-controlled, single and multiple dose study of intravenous thymosin beta4 in healthy volunteers.\" Ann N Y Acad Sci, 2010;1194:223-9. PMID: 20536472.", "pmid": "20536472" }, { "type": "Animal", "citation": "Caers J, et al. \"Thymosin beta4 in multiple myeloma: friend or foe.\" Ann N Y Acad Sci, 2010;1194:125-9. PMID: 20536459.", "pmid": "20536459" }, { "type": "Human", "citation": "Sosne G, et al. \"Thymosin β4 significantly improves signs and symptoms of severe dry eye in a phase 2 randomized trial.\" Cornea, 2015;34(5):491-6. PMID: 25826322.", "pmid": "25826322" }, { "type": "Animal", "citation": "Zhang J, et al. \"Thymosin beta4 promotes oligodendrogenesis in the demyelinating central nervous system.\" Neurobiol Dis, 2016;88:85-95. PMID: 26805386.", "pmid": "26805386" }, { "type": "Animal", "citation": "Li X, et al. \"Effects of exogenous thymosin β4 on carbon tetrachloride-induced liver injury and fibrosis.\" Sci Rep, 2017;7(1):5872. PMID: 28724974.", "pmid": "28724974" }, { "type": "Human", "citation": "Jiang Y, et al. \"Serum thymosin beta4 as a noninvasive biomarker in patients with nonalcoholic steatohepatitis.\" Rev Esp Enferm Dig, 2018;110(1):19-24. PMID: 29271227.", "pmid": "29271227" }, { "type": "Animal", "citation": "Scheller I, et al. \"Thymosin β4 is essential for thrombus formation by controlling the G-actin/F-actin equilibrium in platelets.\" Haematologica, 2022;107(12):2846-2858. PMID: 34348450.", "pmid": "34348450" }, { "type": "Human", "citation": "Sosne G, et al. \"0.1% RGN-259 (Thymosin ß4) Ophthalmic Solution Promotes Healing and Improves Comfort in Neurotrophic Keratopathy Patients in a Randomized, Placebo-Controlled, Double-Masked Phase III Clinical Trial.\" Int J Mol Sci, 2022;24(1). PMID: 36613994.", "pmid": "36613994" }, { "type": "Animal", "citation": "Hao M, et al. \"Upregulated Tβ4 expression in inflammatory bowel disease impairs the intestinal mucus barrier by inhibiting autophagy in mice.\" Exp Cell Res, 2024;434(1):113871. PMID: 38049080.", "pmid": "38049080" }, { "type": "pubmed", "citation": "Guarnera G, et al. \"Thymosin beta-4 and venous ulcers: clinical remarks on a European prospective, randomized study on safety, tolerability, and enhancement on healing.\" Ann N Y Acad Sci, 2007;1112:407-12. PMID: 17495250.", "pmid": "17495250" }, { "type": "clinical-trial", "citation": "ReGenTree. \"Assessment of the Safety and Efficacy of RGN-259 Ophthalmic Solutions for Dry Eye Syndrome\" (phase 3, thymosin β4 eye drops). ClinicalTrials.gov NCT03937882; completed October 7, 2021." } ], "interactionCoverage": "partial", "related": [ "tb-500", "bpc-157", "ghk-cu" ], "lastReviewed": "2026-09-27", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.3", "named": true, "wording": "Thymosin-ß4 and its derivatives", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.3", "named": true, "wording": "Thymosin-ß4 and its derivatives", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "thymulin", "name": "Thymulin", "aliases": [ "FTS", "Facteur Thymique Sérique", "Serum Thymic Factor" ], "tier": "mid", "category": "immune", "subcategory": "zinc-dependent thymic nonapeptide", "class": "A 9-amino-acid thymic peptide requiring zinc for biological activity.", "tagline": "A zinc-dependent thymic nonapeptide, measured in people far more often than it has ever been given to them.", "oneLiner": "A natural nine-amino-acid thymic hormone that is inert without a bound zinc ion, used mainly as a marker of zinc and thymic status.", "sequence": "pyroGlu-Ala-Lys-Ser-Gln-Gly-Gly-Ser-Asn", "molecularFormula": "C33H54N12O15", "molecularWeight": 858.86, "halfLife": { "value": null, "unit": null, "range": "about 10 minutes in sheep; not measured in people", "source": { "type": "pmid", "pmid": "8040352", "cite": "Davis SL, et al. \"Concentrations of thymulin in unextracted serum from pigs, sheep and cattle as measured by ELISA.\" J Immunoassay, 1994;15(2):191-211. PMID: 8040352." } }, "fdaStatus": "research-only", "approvalDetails": "Not approved as a medicine anywhere. No application appears in FDA's Drugs@FDA database; the published human record is four patients given it intravenously in 1983 plus laboratory work on patients' cells.", "mechanism": "Zinc-bound thymulin promotes T-cell maturation (particularly CD4+ and CD8+ differentiation from thymic precursors), enhances NK cell cytotoxicity, and modulates IL-2 production. Activity absolutely depends on zinc binding — in zinc-deficient states serum immunoreactive thymulin remains but loses biological activity.", "primaryUses": [ "Marker of zinc status and thymic function (research)", "Immune modulation (animal studies)" ], "typicalDose": { "range": "research-only", "unit": "", "frequency": "varies", "route": "subcutaneous (community)", "notes": "No human clinical dosing standard." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Dardenne M, et al. \"Contribution of zinc and other metals to the biological activity of the serum thymic factor.\" Proc Natl Acad Sci U S A, 1982;79(17):5370-3. PMID: 6957870.", "pmid": "6957870" }, { "type": "pubmed", "citation": "Prasad AS, et al. \"Serum thymulin in human zinc deficiency.\" J Clin Invest, 1988;82(4):1202-10. PMID: 3262625.", "pmid": "3262625" }, { "type": "pubmed", "citation": "Palmer AC, et al. \"Prenatal and childhood exposures are associated with thymulin concentrations in young adolescent children in rural Nepal.\" J Dev Orig Health Dis, 2020;11(2):127-135. PMID: 31475652.", "pmid": "31475652" }, { "type": "pubmed", "citation": "Dokhelar MC, et al. \"Effect of a synthetic thymic factor (facteur thymique serique) on natural killer cell activity in humans.\" Int J Immunopharmacol, 1983;5(4):277-82. PMID: 6195118.", "pmid": "6195118" }, { "type": "pubmed", "citation": "Kanemaru H, et al. \"Thymulin restrains age-associated myeloid inflammation and enhances cancer immunotherapy.\" Nat Commun, 2026;17(1). PMID: 42481458.", "pmid": "42481458" }, { "type": "other", "citation": "US FDA, Drugs@FDA (openFDA): no application for thymulin. Read September 30, 2026." }, { "type": "pubmed", "citation": "Nasseri B, et al. \"Thymulin treatment attenuates inflammatory pain by modulating spinal cellular and molecular signaling pathways.\" Int Immunopharmacol, 2019;70:225-234. PMID: 30851702.", "pmid": "30851702" }, { "type": "pubmed", "citation": "Wade S, et al. \"Thymulin (Zn-facteur thymique serique) activity in anorexia nervosa patients.\" Am J Clin Nutr, 1985;42(2):275-80. PMID: 3927699.", "pmid": "3927699" }, { "type": "pubmed", "citation": "Davis SL, et al. \"Concentrations of thymulin in unextracted serum from pigs, sheep and cattle as measured by ELISA.\" J Immunoassay, 1994;15(2):191-211. PMID: 8040352.", "pmid": "8040352" } ], "interactionCoverage": "unreviewed", "related": [ "thymosin-alpha-1", "thymopentin", "thymosin-beta-4" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "tirzepatide", "name": "Tirzepatide", "aliases": [ "Mounjaro", "Zepbound", "LY3298176" ], "tier": "full", "category": "metabolic", "subcategory": "GLP-1/GIP dual agonist", "class": "Dual agonist at GLP-1 and GIP receptors with a fatty acid side chain for weekly dosing.", "tagline": "A once-weekly GLP-1/GIP dual agonist that produced unprecedented weight loss in SURMOUNT trials — up to ~21% at highest dose.", "oneLiner": "A 39-amino-acid synthetic peptide with balanced agonism at GIP and GLP-1 receptors, engineered for a ~5-day half-life via C20 fatty acid conjugation.", "sequence": "YX1EGTFTSDYSIX2LDKIAQKAFVQWLIAGGPSSGAPPPS (X1=Aib, X2=Aib, with C20 diacid at Lys20)", "molecularFormula": "C225H348N48O68", "molecularWeight": 4813.53, "halfLife": { "value": 5, "unit": "days", "range": "~5 days", "notes": "Albumin binding via fatty acid side chain extends half-life; steady state reached in ~4 weeks." }, "fdaStatus": "approved", "approvalDetails": "FDA-approved as Mounjaro (T2DM, May 2022) and Zepbound (chronic weight management, November 2023). Manufactured by Eli Lilly.", "mechanism": "Dual agonist at GIP and GLP-1 receptors. GLP-1 effects include enhanced insulin secretion, reduced glucagon, slowed gastric emptying, and central appetite suppression. GIP contribution is still being characterized but appears to enhance the metabolic effects and may improve GI tolerability compared with GLP-1 monoagonism. Produced greater weight loss than semaglutide in head-to-head SURPASS-2 and SURMOUNT-5 trials.", "primaryUses": [ "Type 2 diabetes mellitus", "Chronic weight management (BMI ≥30, or ≥27 with comorbidity)", "Obstructive sleep apnea (Zepbound expanded indication, December 2024)" ], "typicalDose": { "range": "2.5–15", "unit": "mg", "frequency": "weekly", "route": "subcutaneous", "notes": "Titrated over 20+ weeks. Maximum dose 15 mg weekly. Maintenance typically 10 or 15 mg." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Mounjaro (tirzepatide) Prescribing Information. Eli Lilly." }, { "type": "fda-pi", "citation": "Zepbound (tirzepatide) Prescribing Information. Eli Lilly." }, { "type": "clinical-trial", "citation": "Jastreboff AM, et al. \"Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1).\" N Engl J Med, 2022;387:205-216. PMID: 35658024.", "pmid": "35658024" }, { "type": "pubmed", "citation": "Aronne LJ, et al. \"Tirzepatide as Compared with Semaglutide for the Treatment of Obesity.\" N Engl J Med, 2025;393(1):26-36. PMID: 40353578.", "pmid": "40353578" }, { "type": "pubmed", "citation": "Malhotra A, et al. \"Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity.\" N Engl J Med, 2024;391(13):1193-1205. PMID: 38912654.", "pmid": "38912654" }, { "type": "pubmed", "citation": "Jastreboff AM, et al. \"Tirzepatide for Obesity Treatment and Diabetes Prevention.\" N Engl J Med, 2025;392(10):958-971. PMID: 39536238.", "pmid": "39536238" }, { "type": "pubmed", "citation": "Garvey WT, et al. \"Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial.\" Lancet, 2023;402(10402):613-626. PMID: 37385275.", "pmid": "37385275" }, { "type": "pubmed", "citation": "Nauck MA, et al. \"Tirzepatide, a dual GIP/GLP-1 receptor co-agonist for the treatment of type 2 diabetes with unmatched effectiveness regrading glycaemic control and body weight reduction.\" Cardiovasc Diabetol, 2022;21(1):169. PMID: 36050763.", "pmid": "36050763" }, { "type": "pubmed", "citation": "Del Prato S, et al. \"Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial.\" Lancet, 2021;398(10313):1811-1824. PMID: 34672967.", "pmid": "34672967" }, { "type": "pubmed", "citation": "Frías JP, et al. \"Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes.\" N Engl J Med, 2021;385(6):503-515. PMID: 34170647.", "pmid": "34170647" } ], "interactionCoverage": "full", "related": [ "semaglutide", "retatrutide", "liraglutide" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-18", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "monitoring": "markers of semaglutide and tirzepatide, in and out of competition" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "monitoring": "GLP-1 receptor agonists: semaglutide and tirzepatide, in and out of competition" } ], "moleculeClass": "peptide" }, { "id": "trevogrumab", "name": "Trevogrumab", "aliases": [ "REGN1033", "SAR391786" ], "tier": "stub", "category": "pipeline", "subcategory": "anti-myostatin monoclonal antibody (muscle-sparing adjunct)", "class": "A fully human monoclonal antibody against myostatin (GDF-8), originally developed by Regeneron in partnership with Sanofi.", "tagline": "⚠ Monoclonal antibody — not a classical peptide. A Regeneron anti-myostatin fully human IgG (~150 kDa) being tested as a muscle-sparing adjunct to GLP-1 therapy — CONVERGE combination program with semaglutide in obesity; earlier sarcopenia programs were deprioritized in favor of the obesity opportunity. Included here because it's widely discussed alongside peptides in muscle-sparing conversations.", "oneLiner": "A fully human monoclonal antibody developed by Regeneron that binds and neutralizes myostatin (GDF-8), reviving prior Phase 2 sarcopenia work within a new \"muscle-sparing adjunct to GLP-1\" positioning following the success of bimagrumab's BELIEVE Phase 2b combination with semaglutide.", "sequence": null, "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": "weeks", "range": "Fc-mediated; weeks", "notes": "Long half-life typical of full-length therapeutic antibodies." }, "fdaStatus": "clinical-trials", "approvalDetails": "Not approved. Regeneron is developing trevogrumab within the CONVERGE program as an adjunct to GLP-1 obesity therapy (paired with semaglutide and/or Regeneron's internal GLP-1 candidate), aiming to preserve lean mass during weight loss. Earlier development in sarcopenia did not advance to approval.", "mechanism": "Binds myostatin (GDF-8) in circulation, preventing engagement with ActRIIB receptors on skeletal muscle and releasing the myostatin-mediated brake on muscle protein synthesis. Unlike receptor-blockers such as bimagrumab, trevogrumab is a ligand-specific neutralizer — potentially avoiding the off-target effects associated with broader ActRII receptor blockade (BMP9/BMP10 pathway).", "primaryUses": [ "Muscle preservation during GLP-1 therapy (Phase 2 / CONVERGE program)", "Historical: sarcopenia (deprioritized)" ], "typicalDose": { "range": "not disclosed", "unit": "mg/kg", "frequency": "monthly (trial protocols)", "route": "intravenous or subcutaneous", "notes": "Phase 2 dosing regimens not publicly disclosed in detail." }, "evidenceLevel": "low", "sources": [ { "type": "manufacturer", "citation": "Regeneron Pharmaceuticals. \"Pipeline update: CONVERGE muscle-sparing program,\" investor presentation 2025–2026." }, { "type": "clinical-trial", "citation": "ClinicalTrials.gov identifier for Regeneron trevogrumab combination trials in obesity." } ], "interactionCoverage": "none-found", "related": [ "bimagrumab", "apitegromab", "semaglutide" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S4.3", "named": false, "wording": "Myostatin- or precursor-neutralizing antibodies", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "An anti-myostatin antibody." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S4.3", "named": false, "wording": "Myostatin- or precursor-neutralizing antibodies", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "An anti-myostatin antibody." } ], "moleculeClass": "antibody", "moleculeClassBasis": "monoclonal antibody" }, { "id": "tripeptide-10-citrulline", "name": "Tripeptide-10 Citrulline", "aliases": [ "T10-C", "Decorinyl (trade name)", "Lys-Asp-Ile-Cit-NH2" ], "tier": "stub", "category": "cosmetic", "subcategory": "topical cosmetic peptide (decorin mimetic)", "class": "A synthetic tetrapeptide (Lys-Asp-Ile-Cit-NH2) consisting of three proteinogenic residues plus a non-proteinogenic C-terminal L-citrulline, modeled on the collagen-binding motif of decorin; the INCI-designated active in Lipotec's Decorinyl® ingredient.", "tagline": "The INCI name for the active peptide in Decorinyl® — a tetrapeptide (KDI-Cit) where the charge pattern (+/−/0/+) reproduces decorin's collagen-binding motif. Separate listing from the \"decorinyl\" trade-name entry to make INCI-level search usable for formulators.", "oneLiner": "A synthetic tetrapeptide (Lys-Asp-Ile-Citrulline-NH2, CAS 960531-53-7) modeled on decorin's collagen-fibril-binding motif; the INCI-registered active in Lipotec's Decorinyl® cosmetic ingredient. The \"Tripeptide-10\" INCI stem names the three proteinogenic residues, with the C-terminal L-citrulline called out separately because citrulline (a ureido amino acid) is not one of the standard twenty. Primary published evidence comes from Puig et al. 2008 (Int J Cosmet Sci), which describes the design rationale and a placebo-controlled trial of a 0.01 % formulation showing a 54 % increase in skin suppleness at 28 days. A separate randomised-controlled study (Raikou et al. 2017) examined the combination with Acetyl Hexapeptide-3 (Argireline). Cosmetic ingredient only; not a drug.", "sequence": "Lys-Asp-Ile-Cit-NH2", "molecularFormula": "C22H42N8O7", "molecularWeight": 530.62, "halfLife": { "value": null, "unit": null, "range": "topical only", "notes": "Systemic absorption from topical cosmetic formulations is minimal." }, "fdaStatus": "research-only", "approvalDetails": "Cosmetic ingredient; not a drug. INCI name: Tripeptide-10 Citrulline. Commonly encountered trade name: Decorinyl® (Lipotec / Lubrizol).", "mechanism": "Mimics the collagen-binding region of decorin, a small leucine-rich proteoglycan (SLRP) that decorates the surface of type I collagen fibrils and regulates lateral fusion and fibril diameter during fibrillogenesis. The four-residue KDIC motif preserves the +/−/0/+ charge pattern of the native decorin binding sequence (with C-terminal citrulline replacing the native neutral residue for stability) and is proposed to occupy the same fibril surface site. In aged and photoaged skin, endogenous decorin is progressively truncated and loses regulatory activity; Tripeptide-10 Citrulline is proposed to partially compensate by re-establishing surface regulation. In-vitro fibrillogenesis assays show narrower, more uniform fibrils in treated samples. Cosmetic clinical evidence is limited but available (Puig 2008, Raikou 2017). Commonly co-formulated with Tripeptide-1 in Trylagen™ or with Acetyl Hexapeptide-8 in wrinkle formulations.", "primaryUses": [ "Topical cosmetic anti-aging formulations (collagen-quality / fibril organization)" ], "typicalDose": { "range": "2–5", "unit": "% (finished formulation, as supplied Decorinyl solution delivering ~0.01 % active)", "frequency": "twice daily", "route": "topical", "notes": "Cosmetic concentrations. Published clinical study used a 0.01 % active-peptide liposomal formulation." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Puig A, García Antón J, Mangues M. \"A new decorin-like tetrapeptide for optimal organization of collagen fibres.\" Int J Cosmet Sci, 2008;30(2):97-104. PMID: 18377618.", "pmid": "18377618" }, { "type": "pubmed", "citation": "Raikou V, Varvaresou A, Panderi I, Papageorgiou E. \"The efficacy study of the combination of tripeptide-10-citrulline and acetyl hexapeptide-3. A prospective, randomized controlled study.\" J Cosmet Dermatol, 2017;16(2):271-278. PMID: 28150423.", "pmid": "28150423" }, { "type": "manufacturer", "citation": "Lipotec / Lubrizol. \"Decorinyl® (Tripeptide-10 Citrulline) technical data sheet.\" CAS 960531-53-7." } ], "interactionCoverage": "none-found", "related": [ "decorinyl", "matrixyl", "argireline" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Sold as a cosmetic ingredient, not a drug. S0 covers pharmacological substances without a drug approval; whether it reaches a topical cosmetic ingredient has not been decided." } ], "moleculeClass": "peptide" }, { "id": "triptorelin", "name": "Triptorelin", "aliases": [ "Trelstar", "Triptodur", "Decapeptyl", "Gonapeptyl" ], "tier": "mid", "category": "sexual-health", "subcategory": "GnRH agonist", "class": "Synthetic decapeptide GnRH agonist with a D-tryptophan at position 6 providing prolonged receptor binding and chemical-castration pharmacology.", "tagline": "A widely used long-acting GnRH agonist — FDA-approved as Trelstar for advanced prostate cancer and as Triptodur for pediatric central precocious puberty; approved internationally (Decapeptyl, Gonapeptyl) for endometriosis, uterine fibroids, and female infertility protocols.", "oneLiner": "A synthetic GnRH agonist differing from endogenous GnRH by a D-Trp substitution at position 6, which resists enzymatic degradation and extends receptor binding. Produces an initial gonadotropin surge followed by sustained GnRHR desensitization and chemical castration. Marketed in the US as Trelstar (1/3/6-month IM depots for prostate cancer) and Triptodur (6-month IM depot for pediatric CPP); extensively used internationally as Decapeptyl/Gonapeptyl for gynecologic indications and IVF downregulation.", "sequence": "pGlu-His-Trp-Ser-Tyr-D-Trp-Leu-Arg-Pro-Gly-NH2", "molecularFormula": "C64H82N18O13", "molecularWeight": 1311.5, "halfLife": { "value": null, "unit": null, "range": "not reported in the sources read", "source": { "type": "none", "note": "searched PubMed on October 1, 2026; no human half-life figure in the sources read" } }, "fdaStatus": "approved", "approvalDetails": "Trelstar, NDA 021288, approved June 29, 2001, for advanced prostate cancer; Triptodur, NDA 208956, approved June 29, 2017. Dosage strengths are not additive and are chosen for the intended interval (Drugs@FDA and the Trelstar label, read October 1, 2026).", "mechanism": "Binds GnRHR on pituitary gonadotrophs; continuous exposure causes receptor desensitization and downregulation after an initial testosterone/estradiol flare. Results in medically reversible chemical castration.", "primaryUses": [ "Advanced prostate cancer (Trelstar — palliative androgen deprivation)", "Central precocious puberty, pediatric (Triptodur)", "Endometriosis (ex-US)", "Uterine leiomyomata (ex-US)", "IVF downregulation in long-protocol controlled ovarian stimulation (ex-US)", "Female breast cancer, premenopausal ovarian suppression (ex-US adjuvant endocrine therapy)" ], "typicalDose": { "range": "3.75-22.5", "unit": "mg", "frequency": "every 4, 12 or 24 weeks by strength", "route": "intramuscular", "notes": "Trelstar label: a single intramuscular injection into either buttock; 3.75 mg every 4 weeks, 11.25 mg every 12 weeks or 22.5 mg every 24 weeks. The strengths are NOT additive and must be chosen for the intended interval." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Trelstar (triptorelin pamoate) prescribing information, sections 1 and 2 (DailyMed SPL version 20, effective June 30, 2026; read October 1, 2026)." }, { "type": "pubmed", "citation": "Gravina A, et al. \"Ten-year update of HOBOE phase III trial comparing triptorelin plus either tamoxifen or letrozole or zoledronic acid + letrozole in premenopausal hormone receptor-positive early breast cancer patients.\" ESMO Open, 2025;10(1):104085. PMID: 39754976.", "pmid": "39754976" }, { "type": "pubmed", "citation": "Yu X, et al. \"A Phase 3, Open-Label, Single-Arm Trial of the Efficacy and Safety of Triptorelin 6-Month Formulation in Chinese Children with Central Precocious Puberty.\" Adv Ther, 2024;41(12):4537-4556. PMID: 39412628.", "pmid": "39412628" }, { "type": "pubmed", "citation": "Zenaty D, et al. \"A 6-Month Trial of the Efficacy and Safety of Triptorelin Pamoate (11.25 mg) Every 3 Months in Children with Precocious Puberty: A Retrospective Comparison with Triptorelin Acetate.\" Horm Res Paediatr, 2016;86(3):188-195. PMID: 27603324.", "pmid": "27603324" }, { "type": "pubmed", "citation": "Li X, et al. \"Assessment of Two Formulations of Triptorelin in Chinese Patients with Endometriosis: A Phase 3, Randomized Controlled Trial.\" Adv Ther, 2022;39(10):4663-4677. PMID: 35947347.", "pmid": "35947347" }, { "type": "pubmed", "citation": " \"Comparable clinical outcome using the GnRH antagonist ganirelix or a long protocol of the GnRH agonist triptorelin for the prevention of premature LH surges in women undergoing ovarian stimulation.\" Hum Reprod, 2001;16(4):644-51. PMID: 11278211.", "pmid": "11278211" }, { "type": "pubmed", "citation": "Klotz L, et al. \"The efficacy and safety of degarelix: a 12-month, comparative, randomized, open-label, parallel-group phase III study in patients with prostate cancer.\" BJU Int, 2008;102(11):1531-8. PMID: 19035858.", "pmid": "19035858" }, { "type": "fda-pi", "citation": "Triptodur (triptorelin) Prescribing Information. Azurity Pharmaceuticals." } ], "interactionCoverage": "partial", "related": [ "leuprolide", "goserelin", "histrelin", "degarelix", "gonadorelin" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "prohibited", "section": "S2.2.1", "named": true, "wording": "triptorelin", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "malesOnly": true, "monitoring": "GnRH analogues in female athletes under 18, in and out of competition" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "prohibited", "section": "S2.2.1", "named": true, "wording": "triptorelin", "specified": false, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "malesOnly": true, "monitoring": "GnRH analogues in female athletes under 18, in and out of competition" } ], "moleculeClass": "peptide" }, { "id": "ularitide", "name": "Ularitide", "aliases": [ "Urodilatin", "INN-00835", "URO-7", "chemically synthesized urodilatin" ], "tier": "full", "category": "cardiovascular", "subcategory": "Natriuretic peptide — guanylate cyclase-A (NPR-A) agonist", "class": "A chemically synthesized version of urodilatin — a 32-residue natriuretic peptide produced in the kidney from the proANP precursor (four additional N-terminal residues compared with circulating ANP). Developed by Cardiorentis as an intravenous treatment for acute decompensated heart failure; the TRUE-AHF phase 3 trial (n=2,157, NEJM 2017) met neither co-primary endpoint. Not approved anywhere.", "tagline": "⚠ Phase 3 failure. Cardiorentis's ularitide, a synthetic copy of the kidney's natriuretic peptide urodilatin, lowered cardiac filling pressures in phase 2, but TRUE-AHF (NEJM 2017, n=2,157) found no effect on cardiovascular death or on the early clinical course. Never approved.", "oneLiner": "A synthetic 32-residue peptide identical to endogenous urodilatin — the kidney's processed form of proANP, which carries the 28-residue ANP sequence plus four extra N-terminal residues (TAPR) and is degraded more slowly than ANP by neprilysin. Developed by Cardiorentis AG as an intravenous therapy for acute decompensated heart failure. Phase 2 trials lowered wedge pressure and eased breathlessness; the pivotal TRUE-AHF trial (Packer et al, NEJM 2017; n=2,157) randomised patients to a 48-hour infusion of 15 ng/kg/min or placebo and found no difference in cardiovascular death (21.7% vs 21.0%) or in the 48-hour hierarchical clinical composite. A small 2024 trial in refractory cirrhotic ascites was stopped at interim analysis. Not approved in any jurisdiction.", "sequence": "TAPRSLRRSSCFGGRMDRIGAQSGLGCNSFRY (32 residues; disulfide bond Cys11-Cys27; the 4-residue TAPR- N-terminal extension is the kidney-processed signature)", "molecularFormula": "C145H234N52O44S3", "molecularWeight": 3505.9, "halfLife": { "value": 5.6, "unit": "minutes", "range": "about 5.6 minutes (plasma, healthy volunteers, IV infusion)", "notes": "Measured during graded infusions in 12 healthy subjects (Carstens 1998): total clearance about 5.4 L/min and under 1% recovered in urine. Every trial gave it as a continuous intravenous infusion." }, "fdaStatus": "discontinued", "approvalDetails": "Not FDA-approved: Drugs@FDA holds no application for ularitide (read September 30, 2026), and EMA's register of centrally authorised medicines has no entry. The pivotal TRUE-AHF phase 3 trial (NCT01661634) met neither co-primary endpoint (NEJM 2017); a 2024 investigator-initiated trial in refractory cirrhotic ascites (EudraCT 2019-002268-28) was terminated after interim analysis.", "mechanism": "Agonist at natriuretic peptide receptor A (NPR-A / guanylyl cyclase A), the receptor ANP and nesiritide act on, raising cyclic GMP. It increases sodium excretion and urine flow by raising glomerular filtration and inhibiting distal sodium reabsorption, relaxes vessels (lower wedge pressure, right atrial pressure and systemic vascular resistance), and lowers blood pressure in proportion to the dose. The TAPR N-terminal extension makes it a poorer neprilysin substrate than ANP, but clearance is still rapid (plasma half-life about 5.6 minutes in healthy volunteers). In TRUE-AHF it lowered systolic blood pressure and NT-proBNP more than placebo without changing troponin T, cardiovascular mortality over a median 15 months, or the 48-hour clinical composite.", "primaryUses": [ "⚠ Investigational (never approved). Evaluated for acute decompensated heart failure in the TRUE-AHF phase 3 trial, which met neither co-primary endpoint. Smaller trials in acute kidney failure, liver transplantation and refractory cirrhotic ascites found no significant benefit. No current indication." ], "typicalDose": { "range": "15", "unit": "ng/kg/min for 48 hours (TRUE-AHF dosing regimen)", "frequency": "continuous 48-hour IV infusion", "route": "intravenous", "notes": "⚠ Investigational dosing only. TRUE-AHF used a fixed 48-hour infusion at 15 ng/kg/min; the phase 2 SIRIUS trials used 7.5–30 ng/kg/min for 24 hours. No approved product has ever existed." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Packer M, et al. \"Effect of Ularitide on Cardiovascular Mortality in Acute Heart Failure.\" N Engl J Med, 2017;376(20):1956-1964. PMID: 28402745.", "pmid": "28402745" }, { "type": "pubmed", "citation": "Packer M, et al. \"Rationale for and design of the TRUE-AHF trial: the effects of ularitide on the short-term clinical course and long-term mortality of patients with acute heart failure.\" Eur J Heart Fail, 2017;19(5):673-681. PMID: 27862700.", "pmid": "27862700" }, { "type": "pubmed", "citation": "Mitrovic V, et al. \"Effects of the renal natriuretic peptide urodilatin (ularitide) in patients with decompensated chronic heart failure: a double-blind, placebo-controlled, ascending-dose trial.\" Am Heart J, 2005;150(6):1239. PMID: 16338265.", "pmid": "16338265" }, { "type": "pubmed", "citation": "Mitrovic V, et al. \"Haemodynamic and clinical effects of ularitide in decompensated heart failure.\" Eur Heart J, 2006;27(23):2823-32. PMID: 17074775.", "pmid": "17074775" }, { "type": "pubmed", "citation": "Lüss H, et al. \"Renal effects of ularitide in patients with decompensated heart failure.\" Am Heart J, 2008;155(6):1012.e1-8. PMID: 18513512.", "pmid": "18513512" }, { "type": "pubmed", "citation": "Kentsch M, et al. \"Haemodynamic and renal effects of urodilatin in healthy volunteers.\" Eur J Clin Invest, 1992;22(5):319-25. PMID: 1317296.", "pmid": "1317296" }, { "type": "pubmed", "citation": "Carstens J, et al. \"Effect of urodilatin infusion on renal haemodynamics, tubular function and vasoactive hormones.\" Clin Sci (Lond), 1997;92(4):397-407. PMID: 9176040.", "pmid": "9176040" }, { "type": "pubmed", "citation": "Carstens J, et al. \"Metabolism and action of urodilatin infusion in healthy volunteers.\" Clin Pharmacol Ther, 1998;64(1):73-86. PMID: 9695722.", "pmid": "9695722" }, { "type": "pubmed", "citation": "Bestle MH, et al. \"Cardiovascular, endocrine, and renal effects of urodilatin in normal humans.\" Am J Physiol, 1999;276(3):R684-95. PMID: 10070128.", "pmid": "10070128" }, { "type": "pubmed", "citation": "Carstens J, et al. \"Renal effects of urodilatin in healthy subjects are independent of blockade of the cyclooxygenase and angiotensin II receptor.\" Scand J Clin Lab Invest, 2008;68(1):2-10. PMID: 17852806.", "pmid": "17852806" }, { "type": "pubmed", "citation": "Carstens J, et al. \"Renal effects of a urodilatin infusion in patients with liver cirrhosis, with and without ascites.\" J Am Soc Nephrol, 1998;9(8):1489-98. PMID: 9697672.", "pmid": "9697672" }, { "type": "pubmed", "citation": "Gantzel RH, et al. \"Randomized clinical trial on safety of the natriuretic peptide ularitide as treatment of refractory cirrhotic ascites.\" Hepatol Commun, 2024;8(7). PMID: 38934679.", "pmid": "38934679" }, { "type": "pubmed", "citation": "Langrehr JM, et al. \"Prophylactic use of low-dose urodilatin for prevention of renal impairment following liver transplantation: a randomized placebo-controlled study.\" Clin Transplant, 1997;11(6):593-8. PMID: 9408691.", "pmid": "9408691" }, { "type": "pubmed", "citation": "Herbert MK, et al. \"Concomitant treatment with urodilatin (ularitide) does not improve renal function in patients with acute renal failure after major abdominal surgery--a randomized controlled trial.\" Wien Klin Wochenschr, 1999;111(4):141-7. PMID: 10192146.", "pmid": "10192146" }, { "type": "pubmed", "citation": "Mitrovic V, et al. \"Randomized double-blind clinical studies of ularitide and other vasoactive substances in acute decompensated heart failure: a systematic review and meta-analysis.\" ESC Heart Fail, 2018;5(6):1023-1034. PMID: 30246939.", "pmid": "30246939" }, { "type": "pubmed", "citation": "Drummer C. \"Involvement of the renal natriuretic peptide urodilatin in body fluid regulation.\" Semin Nephrol, 2001;21(3):239-43. PMID: 11320487.", "pmid": "11320487" }, { "type": "pubmed", "citation": "Abassi ZA, et al. \"Hydrolysis of iodine labelled urodilatin and ANP by recombinant neutral endopeptidase EC. 3.4.24.11.\" Br J Pharmacol, 1994;113(1):204-8. PMID: 7812611.", "pmid": "7812611" }, { "type": "pubmed", "citation": "Abassi ZA, et al. \"Pharmacokinetics of ANF and urodilatin during cANF receptor blockade and neutral endopeptidase inhibition.\" Am J Physiol, 1992;263(5 Pt 1):E870-6. PMID: 1443119.", "pmid": "1443119" }, { "type": "pubmed", "citation": "Inserte J, et al. \"Urodilatin limits acute reperfusion injury in the isolated rat heart.\" Cardiovasc Res, 2000;45(2):351-9. PMID: 10728355.", "pmid": "10728355" }, { "type": "fda", "citation": "FDA. Drugs@FDA (openFDA): no application for ularitide or urodilatin. Read September 30, 2026." }, { "type": "other", "citation": "European Medicines Agency. Medicines register (centrally authorised human medicines): no entry for ularitide or urodilatin. Read September 30, 2026." } ], "interactionCoverage": "none-found", "related": [ "nesiritide", "carperitide" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "A discontinued drug: S0's own examples include discontinued drugs." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "A discontinued drug: S0's own examples include discontinued drugs." } ], "moleculeClass": "peptide" }, { "id": "urofollitropin", "name": "Urofollitropin", "aliases": [ "Bravelle", "Fertinex", "Metrodin HP", "uFSH", "highly purified urinary FSH" ], "tier": "stub", "category": "sexual-health", "subcategory": "urinary-derived gonadotropin", "class": "Highly purified urinary-derived human FSH — extracted and purified from the urine of postmenopausal women, historically the only source of therapeutic FSH before recombinant production.", "tagline": "Ferring's Bravelle (and earlier Fertinex) — highly purified urinary-derived FSH used for ovulation induction and IVF controlled ovarian stimulation. FDA-approved 2002; branded Bravelle was withdrawn from the US market in 2015 due to manufacturing/potency concerns but the molecule class remains available via urinary-derived menotropin combination products.", "oneLiner": "Highly purified FSH extracted from the urine of postmenopausal women and further purified by immunoaffinity chromatography to remove LH, TSH, and other urinary glycoproteins. Historically the dominant FSH source for ovulation induction and IVF before recombinant follitropin alfa/beta became available. FDA-approved as Fertinex (1996) and then Bravelle (Ferring, 2002). Branded Bravelle in the United States was voluntarily withdrawn in October 2015 after Ferring identified a manufacturing-related potency variance; the urinary-FSH class remains represented in current practice primarily through urinary-derived menotropin combination products (Menopur, Repronex).", "sequence": null, "molecularFormula": null, "molecularWeight": 30000, "halfLife": { "value": 24, "unit": "hours", "range": "~24 hours", "notes": "Pharmacokinetics comparable to recombinant FSH products." }, "fdaStatus": "approved", "approvalDetails": "FDA-approved as Fertinex (Serono, 1996) and later as Bravelle (Ferring, 2002), both highly purified urinary FSH (uFSH-HP). Indications: ovulation induction in anovulatory infertility; development of multiple follicles during controlled ovarian stimulation for assisted reproduction. The branded Bravelle product was voluntarily withdrawn from the US market in October 2015 by Ferring due to identified manufacturing variance affecting potency assay results; the underlying molecule class (urinary FSH) remains in use through the menotropin combination product Menopur.", "mechanism": "FSHR agonism identical to endogenous and recombinant FSH. Drives follicular recruitment and maturation in women; potency was historically standardized by the Steelman-Pohley rat ovarian-weight bioassay and later by in vitro cell assays.", "primaryUses": [ "Ovulation induction (historical/ex-US)", "IVF controlled ovarian stimulation (historical/ex-US)" ], "typicalDose": { "range": "75–225", "unit": "IU/day", "frequency": "daily", "route": "subcutaneous or intramuscular", "notes": "Ovulation induction: 150 IU SC/IM daily starting dose, titrated. IVF COH: 150–225 IU daily. Dosing practical equivalent of recombinant FSH." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Bravelle (urofollitropin for injection, purified) Prescribing Information. Ferring Pharmaceuticals (historical; US market withdrawal October 2015)." }, { "type": "other", "citation": "Ferring Pharmaceuticals. \"Voluntary Nationwide Recall of Bravelle (urofollitropin for injection, purified) in the United States.\" October 2015." } ], "interactionCoverage": "partial", "related": [ "follitropin-alfa", "follitropin-beta", "follitropin-delta", "menotropin", "hcg" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Follicle-stimulating hormone is not named, and S2.2.1's examples (CG, LH, GnRH agonists, kisspeptin) are testosterone-stimulating hormones, which FSH is not." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Follicle-stimulating hormone is not named, and S2.2.1's examples (CG, LH, GnRH agonists, kisspeptin) are testosterone-stimulating hormones, which FSH is not." } ], "moleculeClass": "protein", "moleculeClassBasis": "FSH" }, { "id": "vancomycin", "name": "Vancomycin", "aliases": [ "Vancocin" ], "tier": "mid", "category": "immune", "subcategory": "glycopeptide antibiotic", "class": "A tricyclic glycopeptide antibiotic produced by Amycolatopsis orientalis, the historical 'drug of last resort' for gram-positive infections.", "tagline": "The IV antibiotic for resistant staphylococci and the oral one for C. difficile, now dosed by drug levels and beaten head-to-head by newer drugs.", "oneLiner": "A glycopeptide antibiotic given intravenously for serious MRSA infections and by mouth for C. difficile; the two routes do not substitute.", "sequence": "Glycopeptide (non-ribosomal peptide, 7 amino acids in heptapeptide core)", "molecularFormula": "C66H75Cl2N9O24", "molecularWeight": 1449.3, "halfLife": { "value": 5, "unit": "hours", "range": "4 to 6 hours with normal kidney function; about 7.5 days without", "source": { "type": "label", "ref": "Vancomycin hydrochloride for injection prescribing information, section 12.3 (DailyMed version 10, effective June 1, 2021; read September 30, 2026)" } }, "fdaStatus": "approved", "approvalDetails": "FDA-approved in intravenous form (several makers) and as Vancocin capsules, NDA 050606, for C. difficile-associated diarrhoea and staphylococcal enterocolitis. The 2020 consensus guideline targets a 24-hour AUC/MIC of 400-600 in serious MRSA infections.", "mechanism": "Binds with high affinity to the D-Ala-D-Ala dipeptide terminus of lipid II (the peptidoglycan precursor), forming a non-covalent complex that sterically prevents both transglycosylation and transpeptidation. This blocks cell wall synthesis. VRE resistance arises from D-Ala-D-Lac substitution, which reduces binding affinity 1000-fold.", "primaryUses": [ "Serious infections with methicillin-resistant staphylococci (IV)", "C. difficile-associated diarrhoea (oral)", "Staphylococcal enterocolitis (oral)" ], "typicalDose": { "range": "15–20", "unit": "mg/kg", "frequency": "every 8–12 hours (IV); 125 mg 4x daily (oral for C. diff)", "route": "intravenous or oral", "notes": "IV for systemic infections. Oral vancomycin is not absorbed and acts locally in the gut for C. difficile." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Vancomycin Hydrochloride for Injection (Mylan Institutional) Prescribing Information, sections Indications, Dosage and Clinical Pharmacology (DailyMed version 10, effective June 1, 2021; read September 30, 2026)." }, { "type": "fda-pi", "citation": "VANCOCIN (vancomycin hydrochloride) capsules Prescribing Information, sections 1 and 2 (DailyMed version 12, effective December 22, 2025; read September 30, 2026)." }, { "type": "pubmed", "citation": "Rybak MJ, et al. \"Therapeutic Monitoring of Vancomycin for Serious Methicillin-resistant Staphylococcus aureus Infections: A Revised Consensus Guideline and Review by the American Society of Health-system Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists.\" Clin Infect Dis, 2020;71(6):1361-1364. PMID: 32658968.", "pmid": "32658968" }, { "type": "pubmed", "citation": "Chavanet P. \"The ZEPHyR study: a randomized comparison of linezolid and vancomycin for MRSA pneumonia.\" Med Mal Infect, 2013;43(11-12):451-5. PMID: 24238896.", "pmid": "24238896" }, { "type": "pubmed", "citation": "Louie TJ, et al. \"Fidaxomicin versus vancomycin for Clostridium difficile infection.\" N Engl J Med, 2011;364(5):422-31. PMID: 21288078.", "pmid": "21288078" }, { "type": "pubmed", "citation": "Juul FE, et al. \"Fecal Microbiota Transplantation Versus Vancomycin for Primary Clostridioides difficile Infection : A Randomized Controlled Trial.\" Ann Intern Med, 2025;178(7):940-947. PMID: 40523286.", "pmid": "40523286" }, { "type": "pubmed", "citation": "Keating JA, et al. \"Oral Vancomycin for Prevention of Recurrent Clostridioides difficile Infection: A Randomized Clinical Trial.\" JAMA Netw Open, 2025;8(7):e2517834. PMID: 40601321.", "pmid": "40601321" }, { "type": "other", "citation": "US FDA, Drugs@FDA (openFDA): VANCOCIN HYDROCHLORIDE capsules, NDA 050606, ANI Pharmaceuticals, prescription. Read September 30, 2026." } ], "interactionCoverage": "label", "related": [ "daptomycin", "ll-37" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-20", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "vasopressin", "name": "Vasopressin", "aliases": [ "Arginine vasopressin", "AVP", "Antidiuretic hormone", "ADH", "Vasostrict", "Pitressin" ], "tier": "full", "category": "cardiovascular", "subcategory": "Vasopressin receptor agonist (V1a / V1b / V2)", "class": "The endogenous mammalian nonapeptide hormone arginine vasopressin (AVP), produced in the supraoptic and paraventricular nuclei of the hypothalamus and secreted from the posterior pituitary; FDA-approved as an exogenous IV vasopressor under the brand name Vasostrict® (Par Pharmaceutical) for vasodilatory shock unresponsive to fluids and catecholamines.", "tagline": "The antidiuretic hormone as an ICU vasopressor (Vasostrict, 2014): added to norepinephrine in shock, it was safe but did not lower mortality in VASST or pooled trials, did better after cardiac surgery, and its price rose steeply after a 2014 rebranding.", "oneLiner": "A cyclic nonapeptide (Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly-NH2 with a disulfide bridge between Cys1 and Cys6) identical in sequence to the endogenous human antidiuretic hormone. Three receptors: V1a (vascular smooth muscle — vasoconstriction), V1b / V3 (anterior pituitary — ACTH release), and V2 (renal collecting duct — aquaporin-2 insertion, water reabsorption). Par Pharmaceutical's Vasostrict® received FDA NDA approval on 17 April 2014 (NDA 204485) via the 505(b)(2) pathway — the first and, at the time, only vasopressin injection USP with an approved NDA. Indication: vasodilatory shock (e.g., post-cardiotomy, septic) refractory to fluids and catecholamines. Dosing: 0.01–0.07 U/min for septic shock; 0.03–0.1 U/min for post-cardiotomy shock, titrated up in 0.005 U/min increments.", "sequence": "Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly-NH2 (disulfide Cys1-Cys6)", "molecularFormula": "C46H65N15O12S2", "molecularWeight": 1084.23, "halfLife": { "value": 10, "unit": "minutes", "range": "≤10 minutes at shock infusion rates (label)", "notes": "Vasostrict label: at 0.01–0.1 units/min in vasodilatory shock, clearance 9–25 mL/min/kg and apparent half-life ≤10 minutes; broken down by proteases. The '10–35 minutes' given here before had no source." }, "fdaStatus": "approved", "approvalDetails": "FDA-approved April 17, 2014 as Vasostrict (NDA 204485) to increase blood pressure in adults with vasodilatory shock who remain hypotensive despite fluids and catecholamines; label infusion rates 0.01–0.07 units/min (septic shock) and 0.03–0.1 units/min (post-cardiotomy). Generic vasopressin injections approved from 2021, and a premixed vasopressin in sodium chloride (NDA 217569) on September 29, 2023 (Drugs@FDA, read September 28, 2026).", "mechanism": "Endogenous agonist at three G-protein-coupled receptors. V1a receptors on vascular smooth muscle couple to Gq / phospholipase C / IP3 / calcium release, producing vasoconstriction — the pharmacologic basis of the vasopressor indication. V2 receptors on renal collecting duct principal cells couple to Gs / adenylate cyclase / cAMP / protein kinase A, driving aquaporin-2 insertion and water reabsorption. V1b / V3 receptors in anterior pituitary corticotrophs potentiate CRH-driven ACTH release. In vasodilatory shock, endogenous vasopressin is relatively deficient (the \"vasopressin-deficiency\" hypothesis) and sensitivity to catecholamines is reduced by receptor desensitisation; exogenous vasopressin engages an independent vasoconstrictor pathway to restore mean arterial pressure. Clinical dosing is titrated well below anti-diuretic thresholds but V2-mediated free-water retention and hyponatremia remain concerns at prolonged infusion.", "primaryUses": [ "Vasodilatory shock unresponsive to fluids and catecholamines (FDA-approved)", "Septic shock as adjunct / catecholamine-sparing agent (Surviving Sepsis Campaign guideline)", "Post-cardiotomy vasodilatory shock", "Cardiac arrest (previously in ACLS algorithms; removed 2015)" ], "typicalDose": { "range": "0.01–0.1", "unit": "units/minute (continuous IV infusion)", "frequency": "continuous infusion", "route": "intravenous", "notes": "Septic shock: start 0.01 U/min, titrate up to 0.07 U/min max. Post-cardiotomy shock: start 0.03 U/min, titrate up to 0.1 U/min max. After 8 hours of target MAP without catecholamines, taper by 0.005 U/min every hour. Contraindicated with 8-L-arginine hypersensitivity. Watch for skin / digital / mesenteric ischemia and hyponatremia from V2-mediated free-water retention." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Vasostrict (vasopressin injection) Prescribing Information. Par Health USA (DailyMed, read 2026-09-28)." }, { "type": "fda-pi", "citation": "US FDA, Drugs@FDA: Vasostrict NDA 204485 (April 17, 2014); generic vasopressin ANDAs 2021-2023; vasopressin in sodium chloride NDA 217569 (September 29, 2023) (read 2026-09-28)." }, { "type": "Human", "citation": "Russell JA, et al. \"Vasopressin versus norepinephrine infusion in patients with septic shock.\" N Engl J Med, 2008;358(9):877-87. PMID: 18305265.", "pmid": "18305265" }, { "type": "Human", "citation": "Hajjar LA, et al. \"Vasopressin versus Norepinephrine in Patients with Vasoplegic Shock after Cardiac Surgery: The VANCS Randomized Controlled Trial.\" Anesthesiology, 2017;126(1):85-93. PMID: 27841822.", "pmid": "27841822" }, { "type": "Human", "citation": "Hajjar LA, et al. \"Vasopressin Versus Norepinephrine for the Management of Septic Shock in Cancer Patients: The VANCS II Randomized Clinical Trial.\" Crit Care Med, 2019;47(12):1743-1750. PMID: 31609774.", "pmid": "31609774" }, { "type": "Review", "citation": "Nagendran M, et al. \"Vasopressin in septic shock: an individual patient data meta-analysis of randomised controlled trials.\" Intensive Care Med, 2019;45(6):844-855. PMID: 31062052.", "pmid": "31062052" }, { "type": "Human", "citation": "Lauzier F, et al. \"Vasopressin or norepinephrine in early hyperdynamic septic shock: a randomized clinical trial.\" Intensive Care Med, 2006;32(11):1782-9. PMID: 17019548.", "pmid": "17019548" }, { "type": "Human", "citation": "Hwang SJ, et al. \"A randomized controlled trial comparing octreotide and vasopressin in the control of acute esophageal variceal bleeding.\" J Hepatol, 1992;16(3):320-5. PMID: 1487608.", "pmid": "1487608" }, { "type": "Human", "citation": "Sacha GL, et al. \"Association Between Vasopressin Rebranding and Utilization in Patients With Septic Shock.\" Crit Care Med, 2022;50(4):644-654. PMID: 34605778.", "pmid": "34605778" }, { "type": "guideline", "citation": "Evans L, Rhodes A, Alhazzani W, et al. \"Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021.\" Crit Care Med, 2021;49(11):e1063-e1143." } ], "interactionCoverage": "label", "related": [ "terlipressin", "desmopressin", "angiotensin-ii" ], "lastReviewed": "2026-09-28", "publishedAt": "2026-04-19", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S5", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Not named. S5 names desmopressin, a vasopressin analogue, and covers substances with a similar biological effect; the List does not say whether vasopressin itself is one." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S5", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Not named. S5 names desmopressin, a vasopressin analogue, and covers substances with a similar biological effect; the List does not say whether vasopressin itself is one." } ], "moleculeClass": "peptide" }, { "id": "ventfort", "name": "Ventfort", "aliases": [ "Vascular peptide bioregulator", "Vessel-wall peptide preparation" ], "tier": "stub", "category": "longevity", "subcategory": "Khavinson vascular-derived peptide bioregulator", "class": "A vascular-tissue-derived short peptide bioregulator in the Khavinson framework, marketed in Russia for vascular aging and endothelial support.", "tagline": "The Khavinson vascular bioregulator, marketed in Russia for endothelial aging and microcirculation support. Associated with the synthetic KEDG tetrapeptide in some Khavinson-group publications. Russian-language evidence base only; not FDA/EMA approved.", "oneLiner": "A short peptide bioregulator preparation derived from bovine vascular tissue in the Khavinson cytomedine series, marketed in Russia for age-related vascular decline, endothelial dysfunction, and microcirculatory support. The characterized synthetic active tetrapeptide associated with Ventfort in some Khavinson publications is Lys-Glu-Asp-Gly (KEDG). Evidence base and regulatory status are identical to the rest of the Khavinson short-peptide series: Russian nutraceutical status only, no independent Western clinical validation.", "sequence": "Lys-Glu-Asp-Gly (KEDG, reported synthetic active fragment)", "molecularFormula": "C17H30N6O8", "molecularWeight": 446.46, "halfLife": { "value": null, "unit": null, "range": "Not characterized in humans", "notes": "No peer-reviewed Western pharmacokinetic data." }, "fdaStatus": "not-approved-us", "approvalDetails": "Not FDA- or EMA-approved. Sold in Russia and CIS states as a nutraceutical; not a registered medicine in any Western jurisdiction.", "mechanism": "Proposed to support endothelial aging and vascular homeostasis via the Khavinson-framework tissue-specific gene-expression modulation hypothesis. Not independently validated in Western literature.", "primaryUses": [ "Vascular / endothelial aging support (Russian nutraceutical positioning)", "Microcirculatory support (anecdotal)" ], "typicalDose": { "range": "1–2 capsules", "unit": null, "frequency": "1–2 times daily in 20–30 day courses", "route": "oral", "notes": "Russian nutraceutical dosing. No controlled efficacy evidence." }, "evidenceLevel": "low", "sources": [ { "type": "review", "citation": "Khavinson VK, et al. \"Short peptides and tissue-specific gene expression: the Khavinson bioregulator framework.\" Bull Exp Biol Med, 2011;151:1-8." }, { "type": "review", "citation": "Anisimov VN, Khavinson VK. \"Peptide bioregulation of aging: results and prospects.\" Biogerontology, 2010;11:139-149. PMID: 19830585.", "pmid": "19830585" } ], "interactionCoverage": "none-found", "related": [ "vesugen", "cardiogen", "epithalon" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": "", "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "vesugen", "name": "Vesugen", "aliases": [ "KED tripeptide", "Lys-Glu-Asp", "Vascular tripeptide" ], "tier": "stub", "category": "longevity", "subcategory": "Khavinson synthetic vascular tripeptide", "class": "A synthetic tripeptide (Lys-Glu-Asp, KED) in the Khavinson short-peptide series, studied preclinically for antiatherogenic and vascular-aging effects.", "tagline": "The synthetic KED tripeptide in the Khavinson short-peptide series, studied preclinically for vascular-aging and antiatherogenic effects. Not a registered medicine; research-only in the West, nutraceutical status in Russia. Preclinical evidence only.", "oneLiner": "A synthetic Lys-Glu-Asp (KED) tripeptide in the Khavinson short-peptide series, studied in a small preclinical literature for anti-atherogenic and vascular-protective effects. Reported to modulate endothelial gene expression in cell culture and to reduce aortic atherosclerotic lesion burden in aged rodent models in Khavinson-group publications. Research-only and nutraceutical-grade; no registered-medicine status, no human clinical trials, no independent Western replication.", "sequence": "Lys-Glu-Asp (KED)", "molecularFormula": "C15H26N4O7", "molecularWeight": 374.39, "halfLife": { "value": null, "unit": null, "range": "Short plasma half-life consistent with short-peptide pharmacokinetics; no human data", "notes": "Short peptides in this class typically have plasma half-lives of minutes; Khavinson-framework rationale proposes direct nuclear-target engagement via peptide-DNA interactions, which if correct would uncouple half-life from effect duration." }, "fdaStatus": "research-only", "approvalDetails": "Not FDA- or EMA-approved. Sold as a research chemical in grey-market catalogs and as a nutraceutical supplement in Russia.", "mechanism": "Proposed to modulate vascular endothelial gene expression via the Khavinson-framework short-peptide-DNA-interaction hypothesis, with downstream effects on endothelial nitric oxide synthase (eNOS), adhesion molecule expression, and smooth-muscle proliferation. Preclinical models (rat aortic atherosclerosis, endothelial cell culture) have been reported to show antiatherogenic effects in Khavinson-group publications. Mechanism remains insufficiently characterized at molecular-target resolution.", "primaryUses": [ "Vascular aging research (preclinical)", "Antiatherogenic research (preclinical rodent models)" ], "typicalDose": { "range": "Not established for human use", "unit": null, "frequency": null, "route": null, "notes": "⚠ No human dosing established. Rodent studies have used ~2–10 μg/kg peritoneal or subcutaneous. Any human use would be unregulated and unsupported." }, "evidenceLevel": "low", "sources": [ { "type": "pubmed", "citation": "Khavinson VK, et al. \"Peptide KED reduces experimental atherosclerosis in rats.\" Bull Exp Biol Med, 2013;155:810-812." }, { "type": "review", "citation": "Anisimov VN, Khavinson VK. \"Peptide bioregulation of aging: results and prospects.\" Biogerontology, 2010;11:139-149. PMID: 19830585.", "pmid": "19830585" } ], "interactionCoverage": "unreviewed", "related": [ "ventfort", "cardiogen", "epithalon" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "vip", "name": "VIP", "aliases": [ "Vasoactive Intestinal Peptide", "Aviptadil" ], "tier": "mid", "category": "immune", "subcategory": "neuropeptide", "class": "Endogenous 28-amino-acid peptide in the secretin/glucagon superfamily, acting as a neurotransmitter, hormone, and immune modulator.", "tagline": "Vasoactive intestinal peptide, a 28-amino-acid gut and lung peptide whose synthetic form, aviptadil, was tested in COVID-19 respiratory failure: the 461-patient TESICO trial was stopped for futility, while a 196-patient trial missed its primary end point and reported better day-60 survival. Infused into people with migraine it brings attacks on. Not approved in the US.", "oneLiner": "Vasoactive intestinal peptide, a 28-amino-acid neuropeptide of the gut, lungs and nervous system that relaxes smooth muscle, widens blood vessels and damps inflammation. Its synthetic form, aviptadil, is investigational and has been given intravenously and by inhalation in trials.", "sequence": "HSDAVFTDNYTRLRKQMAVKKYLNSILN-NH2", "molecularFormula": "C147H237N43O43S", "molecularWeight": 3326.8, "halfLife": { "value": null, "unit": null, "range": "Minutes (cleared rapidly from plasma)", "notes": "Short enough that the trials gave it as long infusions or by inhalation.", "source": { "type": "qualitative", "note": "a description with no figure; no half-life measurement is cited for it" } }, "fdaStatus": "clinical-trials", "approvalDetails": "Investigational; Drugs@FDA holds no approved application for aviptadil (openFDA, read September 30, 2026).", "mechanism": "Agonist at VPAC1 and VPAC2 receptors (both Gs-coupled GPCRs), with secondary activity at PAC1. Effects include vascular and bronchial smooth muscle relaxation, stimulation of surfactant production by type II pneumocytes, suppression of inflammatory cytokine release, and modulation of T-cell polarization toward Th2/Treg.", "primaryUses": [ "COVID-19 respiratory failure (investigational, as aviptadil)", "Migraine mechanism research", "Lung and inflammation research" ], "typicalDose": { "range": "600–1,800", "unit": "pmol/kg", "frequency": "a 12-hour infusion daily for 3 days", "route": "intravenous", "notes": "The TESICO regimen for aviptadil; inhaled and intravenous forms have both been trialled." }, "evidenceLevel": "medium", "sources": [ { "type": "fda", "citation": "FDA. Drugs@FDA (openFDA): no approved application for aviptadil (vasoactive intestinal peptide). Read September 30, 2026." }, { "type": "pubmed", "citation": "Brown SM, et al. \"Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial.\" Lancet Respir Med, 2023;11(9):791-803. PMID: 37348524.", "pmid": "37348524" }, { "type": "pubmed", "citation": "Youssef JG, et al. \"The Use of IV Vasoactive Intestinal Peptide (Aviptadil) in Patients With Critical COVID-19 Respiratory Failure: Results of a 60-Day Randomized Controlled Trial.\" Crit Care Med, 2022;50(11):1545-1554. PMID: 36044317.", "pmid": "36044317" }, { "type": "pubmed", "citation": "Esendagli D, et al. \"Inhaled Aviptadil Is a New Hope for Recovery of Lung Damage due to COVID-19.\" Med Princ Pract, 2025;34(2):191-200. PMID: 39870064.", "pmid": "39870064" }, { "type": "pubmed", "citation": "Pellesi L, et al. \"Effect of Vasoactive Intestinal Polypeptide on Development of Migraine Headaches: A Randomized Clinical Trial.\" JAMA Netw Open, 2021;4(8):e2118543. PMID: 34357396.", "pmid": "34357396" }, { "type": "pubmed", "citation": "Delgado M, et al. \"Vasoactive intestinal peptide: a neuropeptide with pleiotropic immune functions.\" Amino Acids, 2013;45(1):25-39. PMID: 22139413.", "pmid": "22139413" }, { "type": "clinicaltrials", "citation": "ClinicalTrials.gov NCT04311697: COVID-AIV, intravenous aviptadil for critical COVID-19 with respiratory failure, completed (registry record read September 30, 2026)." } ], "interactionCoverage": "none-found", "related": [ "thymosin-alpha-1" ], "lastReviewed": "2026-09-30", "publishedAt": "2026-04-18", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "Our entry records an injectable VIP product approved in some EU countries; we have not verified it." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "unsettled", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "Our entry records an injectable VIP product approved in some EU countries; we have not verified it." } ], "moleculeClass": "peptide" }, { "id": "visoluten", "name": "Visoluten", "aliases": [ "Retinal peptide bioregulator", "Eye peptide preparation" ], "tier": "stub", "category": "longevity", "subcategory": "Khavinson retinal-derived peptide bioregulator", "class": "A retinal-tissue-derived short peptide bioregulator in the Khavinson framework, marketed in Russia for retinal aging and age-related macular change.", "tagline": "The Khavinson retinal bioregulator preparation, marketed in Russia for age-related retinal change including macular degeneration support. Evidence base is Russian-language Khavinson-group studies. Not FDA- or EMA-approved.", "oneLiner": "A retinal-tissue-derived short peptide preparation in the Khavinson cytomedine series. Marketed in Russia for age-related retinal decline. Evidence for efficacy in age-related macular degeneration or diabetic retinopathy is limited to Russian-language studies from the Khavinson group and affiliated ophthalmology centers, with minimal methodological rigor by Western standards.", "sequence": "Not definitively disclosed", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": null, "range": "Not characterized", "notes": "No published pharmacokinetic data." }, "fdaStatus": "not-approved-us", "approvalDetails": "Not FDA- or EMA-approved. Russian nutraceutical status only.", "mechanism": "Proposed tissue-specific transcriptional modulation in retinal cells under the Khavinson bioregulator framework. Not mechanistically characterized at molecular-target resolution in peer-reviewed Western literature.", "primaryUses": [ "Age-related retinal aging support (Russian nutraceutical positioning)", "Adjunct in age-related macular degeneration (Russian clinical positioning)", "Adjunct in diabetic retinopathy (Russian clinical positioning)" ], "typicalDose": { "range": "1–2 capsules", "unit": null, "frequency": "1–2 times daily in 20–30 day courses", "route": "oral", "notes": "Russian nutraceutical dosing. No controlled efficacy data." }, "evidenceLevel": "low", "sources": [ { "type": "review", "citation": "Khavinson VK, et al. \"Peptide bioregulators in geriatric ophthalmology.\" Vestn Oftalmol, 2008;124:55-58 (Russian)." }, { "type": "review", "citation": "Anisimov VN, Khavinson VK. \"Peptide bioregulation of aging: results and prospects.\" Biogerontology, 2010;11:139-149. PMID: 19830585.", "pmid": "19830585" } ], "interactionCoverage": "none-found", "related": [ "epithalon", "endoluten", "cerluten" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": "", "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "vk2735", "name": "VK2735", "aliases": [ "VK-2735" ], "tier": "stub", "category": "pipeline", "subcategory": "GLP-1 / GIP dual agonist (Phase 2, SQ and oral)", "class": "A dual GLP-1 / GIP receptor agonist peptide under development by Viking Therapeutics in both subcutaneous and oral-tablet formulations.", "tagline": "Viking's emerging dual GLP-1/GIP agonist — Phase 2 SC data in obesity reported up to ~14.7% placebo-adjusted weight loss at 13 weeks (VENTURE, 2024), with an oral-tablet Phase 2 program initiated 2024; the principal clinical challenger to tirzepatide's mechanism outside the Lilly / Novo axis.", "oneLiner": "A dual GLP-1 / GIP receptor agonist peptide developed by Viking Therapeutics, evaluated in two formulations: a subcutaneous injectable (VENTURE Phase 2 in obesity, 2024; ~14.7% placebo-adjusted weight loss at 13 weeks) and an oral tablet (VK2735-OB-Ph2 initiated late 2024); the most advanced non-Lilly / non-Novo dual GLP-1/GIP asset.", "sequence": null, "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": "days", "range": "supports weekly SC dosing", "notes": "Oral formulation pharmacokinetics not yet disclosed in detail." }, "fdaStatus": "clinical-trials", "approvalDetails": "Not approved. Phase 2 VENTURE (SC) reported February 2024; Phase 2 oral tablet study initiated late 2024. Phase 3 planning disclosed in 2024–2025 corporate updates.", "mechanism": "Balanced agonism at GLP-1 and GIP receptors — mechanistically the same class as tirzepatide, but a distinct molecule. GLP-1 agonism provides glucose-dependent insulin secretion, glucagon suppression, delayed gastric emptying, and central appetite suppression; GIP agonism adds an independent insulinotropic component and appears to modulate lipid handling and nausea tolerability.", "primaryUses": [ "Obesity (Phase 2)", "Type 2 diabetes mellitus (Phase 2)" ], "typicalDose": { "range": "2.5–15", "unit": "mg", "frequency": "once weekly (SC)", "route": "subcutaneous or oral", "notes": "VENTURE SC explored 2.5, 5, 10, and 15 mg weekly cohorts. Oral dosing disclosed separately." }, "evidenceLevel": "medium", "sources": [ { "type": "manufacturer", "citation": "Viking Therapeutics. Press release: VENTURE Phase 2 positive topline results in obesity, February 2024." }, { "type": "clinicaltrials", "citation": "ClinicalTrials.gov NCT05930249 (VENTURE, VK2735 SC Phase 2)." }, { "type": "manufacturer", "citation": "Viking Therapeutics corporate update: oral VK2735 Phase 2 initiation, Q4 2024." } ], "interactionCoverage": "none-found", "related": [ "tirzepatide", "semaglutide", "retatrutide", "maridebart-cafraglutide" ], "lastReviewed": "2026-04-19", "publishedAt": "2026-04-19", "fdaApproved": false, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." }, { "listYear": 2027, "inForce": "2027-01-01", "status": "s0-inferred", "section": "S0", "named": false, "wording": "", "specified": true, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27", "remark": "An investigational drug: S0's own examples include drugs under clinical development." } ], "moleculeClass": "peptide" }, { "id": "vosoritide", "name": "Vosoritide", "aliases": [ "Voxzogo", "BMN 111" ], "tier": "stub", "category": "growth-hormone", "subcategory": "CNP analog (bone growth)", "class": "Vosoritide is a modified C-type natriuretic peptide analog — the first FDA-approved drug specifically for achondroplasia.", "tagline": "The first drug approved for achondroplasia — a CNP analog that stimulates endochondral bone growth by counteracting overactive FGFR3 signaling.", "oneLiner": "A 39-amino-acid modified CNP analog that activates NPR-B receptors on growth plate chondrocytes to counteract FGFR3-mediated growth inhibition, FDA-approved as a daily subcutaneous injection for achondroplasia in children with open growth plates.", "sequence": "Modified CNP-39 with extended N-terminus for protease resistance", "molecularFormula": "C176H290N56O51S3", "molecularWeight": 4100.7, "halfLife": { "value": 30, "unit": "minutes", "range": "25-35 minutes", "notes": "Short half-life requires daily dosing. Navepegritide (weekly PEGylated CNP) was approved in 2026 as a longer-acting alternative." }, "fdaStatus": "approved", "approvalDetails": "FDA-approved November 2021 as Voxzogo for achondroplasia in pediatric patients >=5 years with open epiphyses. Developed by BioMarin.", "mechanism": "Mimics endogenous CNP by binding NPR-B on growth plate chondrocytes. NPR-B activation generates cGMP, which inhibits the overactive FGFR3-MAPK signaling that suppresses bone growth in achondroplasia.", "primaryUses": [ "Achondroplasia in children with open growth plates (FDA-approved)" ], "typicalDose": { "range": "15", "unit": "mcg/kg", "frequency": "once daily", "route": "subcutaneous", "notes": "15 mcg/kg SC daily. Monitor blood pressure initially." }, "evidenceLevel": "high", "sources": [ { "type": "pubmed", "citation": "Savarirayan R, et al. \"Once-daily, subcutaneous vosoritide therapy in children with achondroplasia: a randomised, double-blind, phase 3, placebo-controlled, multicentre trial.\" Lancet, 2020;396(10252):684-692. PMID: 32891212.", "pmid": "32891212" } ], "interactionCoverage": "none-found", "related": [ "navepegritide", "cnp", "somatropin", "lonapegsomatropin" ], "lastReviewed": "2026-04-21", "publishedAt": "2026-04-21", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "ziconotide", "name": "Ziconotide", "aliases": [ "Prialt", "SNX-111", "Omega-Conotoxin MVIIA" ], "tier": "mid", "category": "cognitive", "subcategory": "Venom-derived analgesic peptide", "class": "Ziconotide is a 25-amino-acid peptide derived from cone snail venom — one of the most potent non-opioid analgesics known, FDA-approved for intractable chronic pain.", "tagline": "A cone snail venom peptide turned FDA-approved painkiller — the first non-opioid intrathecal analgesic for severe chronic pain.", "oneLiner": "A synthetic 25-amino-acid peptide derived from the venom of Conus magus that selectively blocks N-type voltage-gated calcium channels (Cav2.2) in spinal pain pathways, FDA-approved as an intrathecal infusion for severe chronic pain refractory to opioids.", "sequence": "CKGKGAKCSRLMYDCCTGSCRSGKC-amide (3 disulfide bonds)", "molecularFormula": "C102H172N36O32S7", "molecularWeight": 2639.14, "halfLife": { "value": 4.6, "unit": "hours", "range": "2.9 to 6.5 hours in cerebrospinal fluid after intrathecal administration (label 12.3)", "source": { "type": "label", "ref": "Prialt (ziconotide) intrathecal infusion prescribing information, boxed warning and sections 1, 2, 4, 5, 6 and 12.3 (DailyMed SPL version 4, effective September 15, 2026; read October 1, 2026)" } }, "fdaStatus": "approved", "approvalDetails": "Prialt, NDA 021060, approved December 28, 2004, for the management of severe chronic pain in adults for whom intrathecal therapy is warranted and who are intolerant of or refractory to other treatment (Drugs@FDA and the label, read October 1, 2026).", "mechanism": "Selectively blocks N-type voltage-gated calcium channels (Cav2.2) on presynaptic nociceptive afferents in the spinal cord dorsal horn, inhibiting release of glutamate, CGRP, and substance P. Does not bind opioid receptors. No tolerance development in long-term studies.", "primaryUses": [ "Severe chronic pain refractory to other analgesics (FDA-approved)", "Cancer-related intractable pain", "Non-opioid analgesic alternative (no respiratory depression, no tolerance)" ], "typicalDose": { "range": "2.4-19.2", "unit": "mcg/day", "frequency": "continuous intrathecal infusion", "route": "intrathecal", "notes": "Prialt label: start at no more than 2.4 mcg/day (0.1 mcg/hr), titrate by up to 2.4 mcg/day no more than 2-3 times a week, to a recommended maximum of 19.2 mcg/day (0.8 mcg/hr) by day 21; intrathecal only, by microinfusion device, never intravenous." }, "evidenceLevel": "high", "sources": [ { "type": "fda-pi", "citation": "Prialt (ziconotide) intrathecal infusion prescribing information, boxed warning and sections 1, 2, 4, 5, 6 and 12.3 (DailyMed SPL version 4, effective September 15, 2026; read October 1, 2026)." }, { "type": "pubmed", "citation": "Staats PS, et al. \"Intrathecal ziconotide in the treatment of refractory pain in patients with cancer or AIDS: a randomized controlled trial.\" JAMA, 2004;291(1):63-70. PMID: 14709577.", "pmid": "14709577" }, { "type": "pubmed", "citation": "Rauck RL, et al. \"A randomized, double-blind, placebo-controlled study of intrathecal ziconotide in adults with severe chronic pain.\" J Pain Symptom Manage, 2006;31(5):393-406. PMID: 16716870.", "pmid": "16716870" }, { "type": "pubmed", "citation": "Wallace MS, et al. \"Intrathecal ziconotide for severe chronic pain: safety and tolerability results of an open-label, long-term trial.\" Anesth Analg, 2008;106(2):628-37, table of contents. PMID: 18227325.", "pmid": "18227325" }, { "type": "pubmed", "citation": "Peraire M, et al. \"Ziconotide and psychosis: from a case report to a scoping review.\" Front Mol Neurosci, 2024;17:1412855. PMID: 39479264.", "pmid": "39479264" }, { "type": "pubmed", "citation": "Olivera BM, et al. \"Peptide neurotoxins from fish-hunting cone snails.\" Science, 1985;230(4732):1338-43. PMID: 4071055.", "pmid": "4071055" } ], "interactionCoverage": "label", "related": [ "beta-endorphin", "enkephalin", "substance-p", "cgrp" ], "lastReviewed": "2026-10-01", "publishedAt": "2026-04-21", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" }, { "id": "zilucoplan", "name": "Zilucoplan", "aliases": [ "Zilbrysq", "RA101495" ], "tier": "stub", "category": "immune", "subcategory": "complement inhibitor peptide", "class": "A 15-amino-acid macrocyclic peptide inhibitor of complement component C5, self-administered subcutaneously for generalized myasthenia gravis.", "tagline": "A self-injectable complement inhibitor — a synthetic macrocyclic peptide that blocks C5 complement activation, FDA-approved for generalized myasthenia gravis as a daily subcutaneous injection.", "oneLiner": "A 15-amino-acid synthetic macrocyclic peptide conjugated to a polyethylene glycol tail, binding complement C5 to prevent cleavage into C5a and C5b and subsequent membrane attack complex (MAC) formation.", "sequence": "Macrocyclic 15-amino-acid peptide (proprietary sequence) with PEG conjugation", "molecularFormula": null, "molecularWeight": null, "halfLife": { "value": null, "unit": null, "range": "Supports once-daily SC dosing", "notes": "PEG conjugation extends half-life to allow daily self-injection. Subcutaneous bioavailability ~87%." }, "fdaStatus": "approved", "approvalDetails": "FDA-approved in 2023 (Zilbrysq, UCB) for generalized myasthenia gravis in anti-acetylcholine receptor antibody-positive adults. First subcutaneous complement inhibitor.", "mechanism": "Binds complement component C5 with high affinity, preventing its cleavage by C5 convertases into C5a (anaphylatoxin) and C5b (initiator of MAC assembly). By blocking terminal complement activation, reduces antibody-mediated destruction of the neuromuscular junction in MG. Unlike eculizumab (monoclonal antibody), zilucoplan is a peptide allowing SC self-administration.", "primaryUses": [ "Generalized myasthenia gravis (AChR antibody-positive)", "Complement-mediated disease research" ], "typicalDose": { "range": "0.3", "unit": "mg/kg", "frequency": "once daily", "route": "subcutaneous (self-injection)", "notes": "Meningococcal vaccination required at least 2 weeks before starting. Supplied as pre-filled syringes." }, "evidenceLevel": "high", "sources": [ { "type": "clinical-trial", "citation": "Howard JF, et al. \"Zilucoplan in patients with generalized myasthenia gravis (RAISE): a randomised, double-blind, placebo-controlled, phase 3 study.\" Lancet Neurol, 2023;22:395-406. PMID: 37059508.", "pmid": "37059508" }, { "type": "fda-pi", "citation": "Zilbrysq (zilucoplan) Prescribing Information. UCB." } ], "interactionCoverage": "none-found", "related": [ "thymosin-alpha-1", "glatiramer" ], "lastReviewed": "2026-04-20", "publishedAt": "2026-04-20", "fdaApproved": true, "approvedElsewhere": null, "wadaStatus": [ { "listYear": 2026, "inForce": "2026-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf", "reviewed": "2026-09-27" }, { "listYear": 2027, "inForce": "2027-01-01", "status": "not-listed", "section": "", "named": false, "wording": "", "specified": null, "source": "https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf", "reviewed": "2026-09-27" } ], "moleculeClass": "peptide" } ]