Arenicin
A marine-lugworm antimicrobial peptide — a rigid beta-hairpin that is especially good at killing hard-to-treat Gram-negative bacteria. Research compounds, not drugs
Arenicin is an antimicrobial peptide from the lugworm, a marine worm that lives in coastal sand. Like the horseshoe-crab peptide tachyplesin, it is a rigid beta-hairpin — two short strands folded back on each other and pinned by a disulfide bond — and it is strongly cationic, so it binds and punches through microbial membranes. Arenicins are broadly antibacterial but are especially valued against Gram-negative bacteria, the class that includes many of the hardest-to-treat, antibiotic-resistant hospital pathogens, and they have even shown activity against the stubborn lung pathogen Mycobacterium abscessus seen in cystic fibrosis. Because the natural peptide is also toxic to human cells, a great deal of work has gone into engineering safer analogs: the arenicin-3 derivative known as AA139 was optimised and advanced into early antibiotic development for Gram-negative infections. Arenicins also, intriguingly, interact with the human complement system, an arm of innate immunity. Arenicins are research peptides; they are not approved medicines and have not been given to people as an approved treatment.
No established human dose Details ↓
Recommended Dosing
No established human dose
Arenicins are lugworm research peptides; no arenicin is an approved treatment. Even the clinically advanced derivative AA139 is an investigational compound.
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What is it?
The lugworm Arenicola marina, a burrowing marine polychaete, defends itself with antimicrobial peptides in its immune cells, and the best known are the arenicins, first described in 2004. Each is a short peptide of twenty-one residues that folds into a rigid beta-hairpin — two antiparallel strands held together, in the natural peptides, by a disulfide bond (arenicin-1 and -2 have one; some isoforms have two). This makes arenicin structurally similar to the horseshoe-crab peptide tachyplesin, and like it, arenicin is strongly cationic and membrane-active.
Arenicin's mechanism is membrane permeabilization: the cationic hairpin inserts into and disrupts the microbial membrane. Its particular strength is activity against Gram-negative bacteria, whose protective outer membrane defeats many antibiotics, and arenicin-1 was shown to insert into mycobacterial lipids and rapidly kill Mycobacterium abscessus — a fast-growing, highly drug-resistant pathogen that causes chronic lung infections in people with cystic fibrosis — without the bacteria developing resistance. Notably, a disulfide-free version of arenicin-1 retained full antibacterial activity while being less toxic to human cells, one of several design lessons the family has taught.
That host toxicity is the central obstacle to turning arenicins into drugs: the natural peptides are strongly hemolytic, so most research redesigns them for a better safety margin. Studies have systematically rearranged the strands, changed the residue symmetry, swapped specific residues, and made linear or backbone-cyclised versions, finding that the arenicin scaffold tolerates a lot of variation while keeping its membrane-disrupting activity. The most advanced product of this work is AA139, an optimised analog of arenicin-3 that was developed as an antibiotic candidate against Gram-negative infections; biophysical studies show AA139 inserts more selectively into bacterial-type membranes than the parent peptide, which underlies its improved potency and lower toxicity.
Arenicins also do something beyond killing microbes: they modulate the human complement system, part of innate immunity. At low concentrations arenicin-1 can stimulate complement activation and at higher concentrations inhibit it, apparently by interacting with the complement proteins C1q and C3 — a dose-dependent, two-way effect shared by several of its analogs (including AA139 and disulfide-free versions). This makes arenicins of interest not only as antibiotics but as templates for complement-targeting drugs, while also flagging complement effects as something to watch in their development.
Through all of this, arenicins remain research peptides. No arenicin is an approved medicine, and even the clinically advanced derivative AA139 is an investigational compound, not an approved drug; material sold online under these names is an unregulated research chemical. Nothing here is a dose or a therapy; this page records what the published science says.
Mechanism of Action
Arenicin is a 21-residue cationic beta-hairpin lugworm antimicrobial peptide (stabilised by a disulfide bond) that permeabilises microbial membranes, with particular strength against Gram-negative bacteria. It is strongly hemolytic (engineered analogs such as AA139 reduce toxicity) and also modulates the human complement system in a dose-dependent way.
Lugworm host defense
A 21-residue cationic beta-hairpin stabilised by a disulfide bond, from the coelomocytes of the marine lugworm Arenicola marina; isoforms arenicin-1/-2/-3 (PMIDs 31234579, 38287360).
Membrane permeabilization
Inserts into and permeabilises microbial membranes, especially Gram-negative bacteria and even mycobacteria; the optimised analog AA139 inserts more selectively (PMIDs 38287360, 35523364).
Complement modulation / engineering
Modulates the human complement system (activating or inhibiting by concentration) via C1q and C3, and is heavily engineered to cut hemolysis while keeping activity (PMIDs 36286436, 33321960).
Published Research
These are studies of arenicins read from their PubMed records on November 7, 2026: arenicin isoforms and disulfide-free derivatives against Mycobacterium abscessus; the membrane activity of the clinical-stage analog AA139; a study of how bacteria resist arenicin derivatives; a structure-activity redesign of arenicin-1; and two studies of arenicins modulating the human complement system. The evidence is in model membranes, bacteria and human cells/serum; no arenicin is an approved treatment.
Arenicin peptides against Mycobacterium abscessus (cystic fibrosis pathogen)
Of three arenicin isoforms and their disulfide-free derivatives, arenicin-1 was the most active against the drug-resistant lung pathogen Mycobacterium abscessus and the safest — non-toxic to human cells and non-hemolytic; it acted by inserting into mycobacterial lipids and rapidly disrupting the membrane without inducing resistance, making it a candidate for cystic-fibrosis-associated infections (an in-vitro study).
Arenicin analogues (including AA139) modulate the complement system
Three therapeutically promising arenicin analogues, including the clinical-stage AA139, were tested for effects on the human complement system; like the natural peptides they could both activate and inhibit complement depending on concentration, with each analog showing a distinct profile — evidence that complement effects should be considered when developing arenicin-based antibiotics (an in-vitro study).
Membrane activity of the arenicin analog AA139
Comparing arenicin-3 with its optimised analog AA139 on model membranes and E. coli showed that small sequence changes alter membrane interaction: AA139 inserts more deeply and selectively into bacterial-type membranes and permeabilises the cytoplasmic membrane more effectively, explaining its greater antibacterial potency and lower toxicity than the parent peptide (a biophysical study).
How bacteria resist an arenicin derivative
Serial passage of E. coli under an arenicin-type beta-sheet peptide produced resistant mutants whose resistance combined several mechanisms — more biofilm, weaker binding of the peptide to endotoxin, and altered membrane permeability and potential — while a chimeric analog retained activity against the resistant clones, mapping resistance routes and how to counter them (an in-vitro study).
A disulfide-free arenicin-1 derivative as a complement modulator
A disulfide-free arenicin-1 derivative (Ar-1-(C/A)) retained the peptide's antimicrobial, and complement-modulating, activities while being less hemolytic than the natural form — supporting arenicin derivatives as both antibacterial and complement-targeting leads (an in-vitro study).
Redesigning arenicin-1: a tolerant scaffold
Rationally redesigned arenicin-1 variants — with rearranged or branched strands, residue substitutions and linear or cyclised backbones — kept the stable beta-hairpin and, in most cases, antimicrobial activity comparable to the natural peptide by permeabilising both bacterial membranes, showing the arenicin scaffold is a flexible template for new anti-infective designs (an in-vitro and simulation study).
No Established Human Dose
Arenicins are lugworm research peptides; no arenicin is an approved treatment. Even the clinically advanced derivative AA139 is an investigational compound. The work here is in model membranes, bacteria and human cells/serum, often with engineered analogs, at experimental amounts that do not carry over to people, so no amount is printed here.
What this rests on: PMID 38287360, PMID 36286436, PMID 35523364.
Educational information, not medical advice. The doses on this page come from approved labels, published studies and, where no study exists, amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no label and no published test that says what forms or vial sizes Arenicin is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
Unknown: no human dose of Arenicin has been established (see No Established Human Dose below), so there is no amount to work out. The reconstitution calculator does the arithmetic for any vial, water and dose.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store Arenicin, before or after mixing. The mixing guide sets out the general rules, with their sources: keep a mixed vial in the fridge, and use it promptly, as the bacteriostatic water label says of any drug dissolved in it. The 28 days often quoted is the limit for an opened multiple-dose vial from a manufacturer, an outer limit set for sterility, not a time a mixed solution has been shown to keep. Nobody has published how long Arenicin stays intact once mixed.
How it is taken
Unknown: with no established human dose, there is no established way of taking Arenicin. What the human studies gave and how is set out under No Established Human Dose.
What to expect, and when
How long it stays in the body: a half-life of not established for humans; a disulfide-stabilised beta-hairpin, more protease-resistant than linear AMPs. After about five half-lives almost none is left.
When effects appear: unknown; no source on this page gives a time to effect for Arenicin. Results reported in the studies are under Published Research.
Source: half-life: PMID 35523364.
Side effects, and when to stop or get help
From the Side Effects section: No approved-treatment human safety data exist for arenicin itself; As membrane-active beta-hairpins, hemolysis and cytotoxicity to host cells are the central safety concern — the natural peptides are strongly hemolytic, and analog design (AA139, disulfide-free forms) aims to reduce it (PMIDs 35523364, 33321960) — research findings, not approved-drug data; Arenicins modulate the human complement system in a dose-dependent way (PMIDs 36286436, 33321960), an effect to weigh in any development; Material sold online as an 'arenicin' is an unregulated research chemical of unverified content. Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Arenicin. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“Arenicins are research peptides and no arenicin is an approved treatment, so there is no established human safety profile; the points below reflect that status and their biology”).
Interactions
Unknown: a PubMed search for human interaction studies of Arenicin (reviewed 2026-11-07) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of Arenicin products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Research Chemical (Not approved drugs: Drugs@FDA and the openFDA label endpoint hold no record, and FDA GSRS and ChEMBL hold no approved-drug record for arenicin peptides (searched November 7, 2026)). Sport: Not on the 2026 List.
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
Arenicins are research peptides and no arenicin is an approved treatment, so there is no established human safety profile; the points below reflect that status and their biology.
Contraindications & Cautions
Arenicins have no approved use and no label. These points reflect their research status.
Legal Status
Arenicins are lugworm antimicrobial peptides used as research compounds; they are not approved drugs in any country.
Frequently Asked Questions
?What is arenicin?
An antimicrobial peptide from the marine lugworm (Arenicola marina). It is a 21-amino-acid cationic beta-hairpin stabilised by a disulfide bond, first described in 2004; isoforms include arenicin-1, -2 and -3 (PMID 31234579).
?How does it work?
It binds and permeabilises microbial membranes, with particular strength against Gram-negative bacteria (and even drug-resistant mycobacteria), and it also modulates the human complement system (PMIDs 38287360, 36286436).
?What is AA139?
AA139 is an optimised analog of arenicin-3 developed as an antibiotic candidate against Gram-negative infections; it inserts more selectively into bacterial membranes than the natural peptide, giving greater potency and lower toxicity. It is investigational, not an approved drug (PMID 35523364).
?Is it approved or available to buy?
No. Arenicins are not approved medicines, have no FDA application or label, and are approved nowhere (AA139 is investigational). Material sold online as an arenicin is an unregulated research chemical. Grey Peptides lists no sellers and recommends no source; this page records the published science.
References
- [mechanism] Casanova M, et al. "Promising antibacterial efficacy of arenicin peptides against the emerging opportunistic pathogen Mycobacterium abscessus." J Biomed Sci, 2024;31(1):18. PMID: 38287360.
- [mechanism] Krenev IA, et al. "In Vitro Modulation of Complement Activation by Therapeutically Prospective Analogues of the Marine Polychaeta Arenicin Peptides." Mar Drugs, 2022;20(10). PMID: 36286436.
- [mechanism] Edwards IA, et al. "Investigations into the membrane activity of arenicin antimicrobial peptide AA139." Biochim Biophys Acta Gen Subj, 2022;1866(8):130156. PMID: 35523364.
- [mechanism] Wang Z, et al. "Resistance response to Arenicin derivatives in Escherichia coli." Appl Microbiol Biotechnol, 2022;106(1):211-226. PMID: 34889983.
- [mechanism] Krenev IA, et al. "Antimicrobial Peptide Arenicin-1 Derivative Ar-1-(C/A) as Complement System Modulator." Mar Drugs, 2020;18(12). PMID: 33321960.
- [mechanism] Orlov DS, et al. "Redesigning Arenicin-1, an Antimicrobial Peptide from the Marine Polychaeta Arenicola marina, by Strand Rearrangement or Branching, Substitution of Specific Residues, and Backbone Linearization or Cyclization." Mar Drugs, 2019;17(6). PMID: 31234579.
- [other] Arenicins are beta-hairpin antimicrobial peptides from the coelomocytes (immune cells) of the marine lugworm Arenicola marina, a polychaete worm, first isolated and described by Ovchinnikova and colleagues (FEBS Lett, 2004). The family includes arenicin-1, -2 and -3; the structure and activities are described in the studies carded on this page (read November 7, 2026).
- [other] US FDA, Drugs@FDA and the openFDA label endpoint, searched November 7, 2026: no application and no label record for arenicin peptides. They are lugworm research antimicrobial peptides, not approved drugs; FDA GSRS and ChEMBL hold no approved-drug record for them.
Sources & Citations
The six studies carded above were read from their PubMed records on November 7, 2026. Arenicin's marine-lugworm (Arenicola marina) origin, its 21-residue disulfide beta-hairpin structure, its membrane-permeabilizing mechanism and Gram-negative strength, its strong hemolysis and the engineering (including the clinical-stage analog AA139) done to reduce it, and its human-complement-modulating activity are from the studies carded here; the discovery is Ovchinnikova et al. (FEBS Lett, 2004). The absence of US approval or a drug record from Drugs@FDA, openFDA, FDA GSRS and ChEMBL was checked the same day. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.