Brevinin
Two large families of frog-skin antimicrobial peptides with a signature 'Rana box' loop — broad-spectrum and membrane-disrupting, but strongly hemolytic. Research compounds, not drugs
Brevinins are among the best-known antimicrobial peptides from frog skin. They come in two large families — brevinin-1 (about 24 amino acids) and the longer brevinin-2 (around 33-34) — first isolated from a Japanese frog in the early 1990s and since found across many frog species. Like other membrane-active peptides they are cationic, amphipathic alpha-helices that disrupt microbial membranes, but brevinins carry a distinctive structural signature: a short disulfide-bridged loop at the C-terminus known as the 'Rana box'. They are notably broad-spectrum, hitting both Gram-positive and Gram-negative bacteria, and family members also show anticancer, anti-inflammatory and wound-healing activity. The flip side is that brevinins are often strongly hemolytic and toxic to host cells, which is the main thing that has kept them out of the clinic. Much of the modern research therefore focuses on engineering brevinins — truncating the Rana box, swapping in D-amino acids or changing charged residues — to keep the antimicrobial punch while lowering the toxicity. Brevinins are research antimicrobial peptides; they are not approved medicines and have not been given to people as a treatment.
No established human dose Details ↓
Recommended Dosing
No established human dose
Brevinins are frog-skin research peptides; none has been given to people as a treatment. The work is in bacteria, cultured cells and animals, often with engineered analogs, at experimental amounts that do not carry over to people.
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What is it?
Frog skin secretes a large arsenal of antimicrobial peptides, and the brevinins are one of its most studied groups. They were first isolated from the Japanese frog Rana brevipoda porsa in the early 1990s, where two families were named: brevinin-1 and the longer brevinin-2. Brevinin-1 peptides are typically around twenty-four residues and brevinin-2 around thirty-three to thirty-four, and both are now known from many frog species, named by species and letter (for example brevinin-1BW, brevinin-1pl, brevinin-2OS, brevinin-2CE).
What sets brevinins apart structurally is the 'Rana box' — a short, disulfide-bridged cyclic loop of about seven residues at the C-terminus that is a hallmark of many frog-skin peptides. The rest of the molecule is a cationic, amphipathic alpha-helix that binds and permeabilises microbial membranes. Brevinins are broadly active, reaching both Gram-positive and Gram-negative bacteria, and several members also disrupt biofilms. Their core mechanism is membrane disruption, confirmed in studies using electron microscopy and membrane-integrity dyes.
The family's great strength — potent, broad membrane activity — is also its great weakness, because that same activity makes many brevinins strongly hemolytic and toxic to mammalian cells, giving them a narrow therapeutic window. A large body of work is therefore devoted to re-engineering them for safety. Studies have shown that truncating the C-terminal Rana box can sharply reduce hemolysis while preserving antibacterial activity, that substituting D-amino acids or arginine, lysine and histidine residues can improve selectivity, and that consensus-sequence design across the brevinin-2 family can generate new peptides active against multidrug-resistant bacteria including carbapenemase producers. Each of these is a structure-activity strategy aimed at decoupling potency from toxicity.
Brevinins are not only antibacterial. Members such as brevinin-1BW and brevinin-1GHd bind bacterial lipopolysaccharide and calm inflammation in cultured immune cells and in mouse models, pointing to anti-inflammatory and endotoxin-neutralising roles, and several brevinins show anticancer activity against human tumour cell lines. These broaden the family's interest as a 'dual-function' anti-infective and immunomodulatory scaffold.
Through all of this, brevinins remain research antimicrobial peptides. No published study has given a brevinin to people as a treatment, none is approved anywhere, and 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
Brevinins are cationic, amphipathic alpha-helical frog-skin antimicrobial peptides with a signature C-terminal disulfide 'Rana box' loop. They disrupt microbial membranes broadly (Gram-positive and Gram-negative), and family members also bind endotoxin, calm inflammation and kill cancer cells; strong hemolysis is the central limitation and the target of extensive engineering.
Broad-spectrum membrane disruption
Cationic amphipathic helices permeabilise both Gram-positive and Gram-negative bacterial membranes and disrupt biofilms (PMIDs 38611812, 38074470).
Endotoxin binding, anti-inflammation, anticancer
Members bind lipopolysaccharide and suppress inflammatory signalling, and several kill cancer cells — a 'dual-function' profile exploited in analog design (PMIDs 36937273, 40458657).
Published Research
These are studies of brevinins read from their PubMed records on November 7, 2026: consensus-sequence design across the brevinin-2 family; rational engineering of a brevinin-2 peptide by Rana-box truncation and chiral substitution; residue-substitution engineering of brevinin-1pl; characterisation of brevinin-1BW's antibacterial and anti-inflammatory activity; and two animal studies of brevinin-1 peptides (an engineered analogue against drug-resistant bacteria in mice, and an LPS-neutralising, anti-inflammatory brevinin-1 in a mouse edema model). The evidence is in bacteria, cells and animals; brevinins have not been given to people as a treatment.
Consensus-sequence Brevinin-2 peptides against multidrug-resistant bacteria
Using the positional frequency of amino acids across the brevinin-2 family, four consensus peptides were synthesised and tested against multidrug-resistant bacteria; one (G37) showed broad-spectrum activity including against carbapenemase-resistant strains and killed quickly, while two others showed selectivity toward Gram-positive versus Gram-negative bacteria — though moderate hemolysis remained a challenge (an in-vitro design study).
Engineering a brevinin-2 peptide to decouple potency from toxicity
Removing the C-terminal Rana box from the strongly hemolytic brevinin-2OS and adding a D-leucine substitution cut hemolysis more than ten-fold while preserving antibacterial activity, improving the therapeutic index against Gram-positive bacteria more than twenty-fold — showing the Rana box drives toxicity rather than activity in this scaffold (an in-vitro SAR study).
Residue substitutions in brevinin-1pl improve selectivity
Substituting arginine, lysine or histidine into the frog peptide brevinin-1pl tuned its antibacterial and anticancer activity: arginine boosted activity against Gram-positive bacteria, while a histidine analogue reduced hemolysis and was low in toxicity to normal human skin cells while still inhibiting breast and lung cancer cell lines — a selectivity-engineering study in vitro.
Brevinin-1BW: antibacterial and anti-inflammatory activity
Brevinin-1BW, isolated from frog skin, strongly inhibited Gram-positive bacteria (including MRSA) by disrupting bacterial membranes, broke up biofilms, bound lipopolysaccharide and reduced the inflammatory response of LPS-treated macrophages — combining direct antibacterial action with anti-inflammatory activity in cultured cells (an in-vitro study).
Brevinin-1 analogue 5R against drug-resistant bacteria (mice)
A brevinin-1-type peptide was redesigned with D-amino-acid and lysine-to-arginine substitutions; the analogue 5R was the most selective and effective against MRSA and other resistant bacteria, from planktonic to biofilm cells, and worked both in vitro and in a mouse model, acting by collapsing the bacterial membrane potential — a preclinical antibacterial result.
A brevinin-1 peptide with LPS-neutralizing, anti-inflammatory activity (mice)
Brevinin-1GHd, an alpha-helical frog peptide, bound bacterial lipopolysaccharide and suppressed the release of inflammatory mediators (TNF-alpha, NO, IL-6, IL-1-beta) by inactivating MAPK signalling in macrophages, and reduced acute paw edema in mice — reported as the first brevinin-1 family peptide with anti-inflammatory activity (a preclinical study).
No Established Human Dose
Brevinins are frog-skin research peptides; none has been given to people as a treatment. The work is in bacteria, cultured cells and animals, often with engineered analogs, at experimental amounts that do not carry over to people. No regulator has approved any dose, and no published human dose exists, so no amount is printed here.
What this rests on: PMID 40867979, PMID 38074470, PMID 36937273.
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 Brevinin 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 Brevinin 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 Brevinin, 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 Brevinin stays intact once mixed.
How it is taken
Unknown: with no established human dose, there is no established way of taking Brevinin. 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; cationic amphipathic peptides subject to proteolysis. After about five half-lives almost none is left.
When effects appear: unknown; no source on this page gives a time to effect for Brevinin. Results reported in the studies are under Published Research.
Source: half-life: PMID 38074470.
Side effects, and when to stop or get help
From the Side Effects section: No human adverse-event data exist: no published study has administered a brevinin to people; Hemolysis and cytotoxicity to host cells are the defining safety concern for brevinins — many natural members are strongly hemolytic, and most engineering work aims specifically to reduce it (PMIDs 40867979, 40458657) — a design issue, not human data; Some brevinins and derivatives are cytotoxic to cancer cells by design (PMID 40458657); selectivity for target over healthy cells is an open research question; Material sold online as a 'brevinin' 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 Brevinin. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“Brevinins are research peptides that have not been given to people as drugs, so there is no human safety profile; the points below reflect that research status and their biology”).
Interactions
Unknown: a PubMed search for human interaction studies of Brevinin (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 Brevinin 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 drugs: Drugs@FDA and the openFDA label endpoint hold no record, and FDA GSRS and ChEMBL hold no approved-drug record for brevinin 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
Brevinins are research peptides that have not been given to people as drugs, so there is no human safety profile; the points below reflect that research status and their biology.
Contraindications & Cautions
Brevinins have no approved use and no label. These points reflect their research status.
Legal Status
Brevinins are frog-skin antimicrobial peptides used as research compounds; they are not drugs and are not approved in any country.
Frequently Asked Questions
?What are brevinins?
Two large families of antimicrobial peptides from frog skin — brevinin-1 (~24 amino acids) and brevinin-2 (~33-34) — first isolated from the Japanese frog Rana brevipoda in 1992. They carry a distinctive C-terminal disulfide 'Rana box' loop (PMID 40867979).
?How do they work?
They are cationic, amphipathic helices that disrupt microbial membranes broadly, killing both Gram-positive and Gram-negative bacteria and breaking up biofilms (PMID 38611812).
?What are they studied for?
As broad-spectrum antibacterial leads, anticancer and anti-inflammatory (endotoxin-neutralising) peptides, and as scaffolds engineered to reduce their toxicity (PMIDs 40867979, 36937273).
?Are they approved or available to buy?
No. Brevinins are not medicines, have no FDA application or label, and are approved nowhere. Material sold online as a brevinin is an unregulated research chemical. Grey Peptides lists no sellers and recommends no source; this page records the published science.
References
- [mechanism] McDowell CM, et al. "In vitro evaluation of novel consensus-sequence-generated Brevinin-2 antimicrobial peptides." Appl Environ Microbiol, 2026;92(10):e0155326. PMID: 42734343.
- [mechanism] Yao A, et al. "Rational Engineering of a Brevinin-2 Peptide: Decoupling Potency from Toxicity Through C-Terminal Truncation and N-Terminal Chiral Substitution." Antibiotics (Basel), 2025;14(8). PMID: 40867979.
- [mechanism] Wang J, et al. "Engineering of antimicrobial peptide Brevinin-1pl: arginine, lysine, and histidine substitutions enhance antimicrobial-anticancer efficacy with reduced cytotoxicity." Front Chem, 2025;13:1579097. PMID: 40458657.
- [mechanism] Chen Z, et al. "Exploration of the Antibacterial and Anti-Inflammatory Activity of a Novel Antimicrobial Peptide Brevinin-1BW." Molecules, 2024;29(7). PMID: 38611812.
- [animal] Zou W, et al. "A promising antibiotic candidate, brevinin-1 analogue 5R, against drug-resistant bacteria, with insights into its membrane-targeting mechanism." Comput Struct Biotechnol J, 2023;21:5719-5737. PMID: 38074470.
- [animal] Tian M, et al. "The first Brevinin-1 antimicrobial peptide with LPS-neutralizing and anti-inflammatory activities in vitro and in vivo." Front Microbiol, 2023;14:1102576. PMID: 36937273.
- [other] Brevinins are antimicrobial peptides from frog (Ranidae) skin secretions, first isolated from the Japanese frog Rana brevipoda porsa by Morikawa, Hagiwara and Nakajima (Biochem Biophys Res Commun, 1992), who named brevinin-1 and brevinin-2. Many members have since been found across frog species; their family structure, the C-terminal 'Rana box' disulfide loop, and their 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 brevinin peptides. They are frog-skin research antimicrobial peptides, not 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. The brevinin family's frog-skin origin, its division into brevinin-1 and brevinin-2, the C-terminal 'Rana box' disulfide loop, its broad-spectrum membrane-disrupting mechanism, its strong hemolysis and the engineering done to reduce it, and its anti-inflammatory and anticancer members are from the studies carded here; the discovery is Morikawa et al. (Biochem Biophys Res Commun, 1992). 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.