KPV peptide (Lys-Pro-Val): lab and animal evidence, FDA review and WADA status

The KPV peptide (Lys-Pro-Val) is a three-amino-acid fragment of alpha-melanocyte-stimulating hormone (alpha-MSH), studied for anti-inflammatory effects. It is not approved by the FDA for any use, and its evidence is limited to lab and animal studies. In a May 2026 review, the FDA found no clinical studies or human exposure data for KPV by any route, so its safety in people is unknown. No registered human trial exists.

Item	Status
US FDA status	Not approved; not part of any FDA-approved drug (FDA briefing, 2026)
Compounding (503A/503B)	Withdrawn from Category 2 by the nominator; not on the 503A Bulks List; FDA staff recommended against adding it (FDA). The Pharmacy Compounding Advisory Committee voted 8–6 (1 abstention) on 2026-07-23 to recommend 503A listing; advisory only, no FDA rule yet (FDA PCAC meeting; counts as reported by trade press)
WADA 2026	Not named; falls under the S0 “non-approved substances” wording, prohibited at all times (WADA)
EU	No authorised product listed by the EMA (per FDA review)
Strongest evidence	Animal (mouse and rat colitis models)
Human trials	None registered (ClinicalTrials.gov)
Last checked	2026-09-30

What changed (October 2026): the July 2026 committee outcome is now stated (as reported, against its own staff’s advice), and the sport sections cover the 2027 WADA List, which names “peptides” in general in S0.

Property	Value
Sequence	H-Lys-Pro-Val-OH (KPV), 3 amino acids
Molecular formula	C16H30N4O4 (PubChem)
Molecular weight	342.43 g/mol (free base); acetate salt 402.5 g/mol
CAS number	67727-97-3
PubChem CID	125672
Half-life	No human or animal pharmacokinetic data found by FDA
Routes studied	Oral (drinking water, nanoparticles), rectal gel, eye drops, gum gel, cell culture
Class	Melanocortin-derived tripeptide; anti-inflammatory research peptide

What is KPV?

KPV is the carboxy-terminal tripeptide of alpha-MSH, a 13-amino-acid hormone cut from the precursor protein proopiomelanocortin. In 1989, researchers in Dallas reported that this fragment reduced chemically induced ear swelling in mice in a dose-related way [Animal] (Hiltz and Lipton, 1989). Interest grew because alpha-MSH darkens skin through the MC1 receptor, while KPV keeps anti-inflammatory activity without that pigment effect, according to a 2008 review by the Münster group (Brzoska et al., 2008). Work since then has focused on the gut, skin, eye and airway. KPV has no United States Adopted Name, and FDA reviewers found products sold under the same common name that were different salts or molecules (FDA, 2026).

How does KPV work?

The mechanism is not settled. FDA reviewers concluded in 2026 that “the molecular targets underlying the pharmacological effects” of KPV “remain unknown” (FDA briefing). The proposed pathways are:

• Uptake by PepT1: In human intestinal and T-cell lines, KPV entered cells through the PepT1 di- and tripeptide transporter, which is induced in the inflamed colon [Lab] (Dalmasso et al., 2008).
• NF-kappaB blockade: In human bronchial cells, KPV entered the nucleus and blocked import of the p65RelA subunit of NF-kappaB, a switch for inflammatory genes [Lab] (Land, 2012).
• No melanocortin receptor binding: In mouse macrophage cells, KPV did not displace MC1 receptor binding at up to 1 mM and did not raise cyclic AMP, yet still inhibited NF-kappaB translocation [Lab] (Mandrika et al., 2001).
• Interleukin-1 beta effects: In mice, KPV reduced white-cell influx in crystal- and IL-1-beta-induced peritonitis, and the effect persisted in mice lacking a working MC1 receptor [Animal] (Getting et al., 2003).

What the research shows about the KPV peptide

Claim	Evidence level	Best study and result
Reduces colitis	Animal	Dalmasso 2008: oral KPV lowered DSS and TNBS colitis in mice
Speeds recovery in colitis	Animal	Kannengiesser 2008: faster weight regain, less inflammation in 2 mouse models
Lowers colitis-linked tumors	Animal	Viennois 2016: fewer tumors in AOM/DSS mice; no effect in a genetic tumor model
Heals the cornea	Animal	Bonfiglio 2006: 8 of 8 rabbit corneas healed by 60 h vs none on placebo
Eases oral mucositis	Animal	Shao 2021: KPV gel improved gum ulcers in rats after chemotherapy
Kills microbes	Lab	Cutuli 2000: inhibited S. aureus and C. albicans in culture
Protects skin cells	Lab	Sung 2025: less dust-induced death and IL-1-beta in keratinocytes
Limits weight gain	Animal	An 2026: less weight gain in high-fat-fed mice
Any effect in people	None	FDA 2026: no human studies found

Gut inflammation

Colitis is the most studied area. In mice given dextran sodium sulfate (DSS) or TNBS, two chemicals that inflame the colon, KPV added to drinking water lowered inflammatory cytokine expression and tissue damage [Animal] (Dalmasso et al., 2008). A Münster group found faster weight regain and less tissue inflammation in DSS and T-cell transfer colitis, and all KPV-treated mice without a functional MC1 receptor survived DSS colitis [Animal] (Kannengiesser et al., 2008). Later mouse and rat work mostly tested delivery systems: nanoparticles in a colon-targeted gel gave similar effect at a KPV concentration 12,000-fold lower than free solution [Animal] (Laroui et al., 2010), and hyaluronic-acid-coated particles reduced mucosal damage and TNF-alpha [Animal] (Xiao et al., 2017). A rectal hydrogel improved TNBS colitis in rats [Animal] (Zhao et al., 2022). None of these designs has been tested in people.

Colitis-associated cancer

In mice treated with a carcinogen plus DSS, KPV lowered tumor number, and the effect vanished in mice lacking PepT1 [Animal] (Viennois et al., 2016). The same paper reported that KPV did not reduce adenomas in APC-Min mice, a genetic tumor model without induced inflammation. The result is a mouse finding, not evidence of cancer prevention in humans.

Skin, eye and mouth

In rabbits with scraped corneas, KPV eye drops sped re-growth of the surface layer, an effect blocked by a nitric oxide inhibitor [Animal] (Bonfiglio et al., 2006). In rats with chemotherapy-induced mouth ulcers, a KPV gel improved food intake, tissue repair and cytokine levels [Animal] (Shao et al., 2021). Skin work is mostly in cells: KPV reduced particulate-induced cell death in human keratinocytes and a 3D skin model [Lab] (Sung et al., 2025). Passive diffusion through donated human skin was below detection; microneedles and electric current raised it [Lab] (Pawar et al., 2017). A 2019 review called wound healing a candidate use that still needs clinical studies (Böhm and Luger, 2019).

Microbes, viruses and metabolism

In culture, KPV reduced growth of Staphylococcus aureus and Candida albicans [Lab] (Cutuli et al., 2000) and lowered HIV-1 expression in infected monocyte cells [Lab] (Barcellini et al., 2000). A 2026 study reported less fat-cell formation in culture and less weight gain in high-fat-fed mice given oral KPV [Lab, Animal] (An et al., 2026). These are single-group findings without independent replication in the sources reviewed here.

Human studies and trials

No completed human trials. A search of ClinicalTrials.gov for “KPV”, “Lys-Pro-Val” and “lysine-proline-valine” returned no study testing the peptide. The FDA review team searched PubMed, Embase and ClinicalTrials.gov and “did not identify data, such as clinical studies, on the use of KPV in humans”; none of the nine references in the compounding nomination studied KPV in people (FDA briefing, 2026). The only work with human tissue used donated skin in a diffusion chamber, which measures penetration, not effect [Lab] (Pawar et al., 2017).

Doses used in studies

Route and species	Amount	Study
Oral, in drinking water; mice	100 µmol/L	Viennois 2016
Eye drops; rabbits	1, 5 or 10 mg/mL solution	Bonfiglio 2006
Cell culture; human intestinal cells	Nanomolar range	Dalmasso 2008
Cell culture; human keratinocytes	50 µg/mL	Sung 2025

No established human dose exists outside approved labels. KPV has no approved label, and animal or cell-culture amounts do not translate to people.

Side effects and safety

There are no human safety data. FDA reviewers found no clinical studies or human exposure data via any route and wrote that “potential safety risks associated with the use of KPV in humans are unknown” (FDA briefing, 2026). Their search of the FDA Adverse Event Reporting System through 2025-12-03 retrieved no reports, and the literature held no case reports. FDA notes that such reporting is voluntary and that compounders generally do not report adverse events, so an empty database is not proof of safety.

The same review found no acute toxicity, repeat-dose toxicity, genotoxicity, reproductive toxicity or carcinogenicity studies of KPV. Theoretical risks it named are immunogenicity (the body forming antibodies against a peptide) and aggregation, since peptides as short as two amino acids can clump, which may change activity. FDA found no data to rule either out.

Product quality is a separate risk. FDA judged both KPV and KPV acetate “not well-characterized” because of inconsistent naming, certificates of analysis that listed purity but no impurity limits, and no microbial testing. It also noted that KPV acetate breaks down to a lysine-proline diketopiperazine under acid, alkaline and oxidative stress. Products sold as “research use only” are outside FDA oversight; in 2026 warning letters the agency said such labels did not stop it from treating peptides as drugs intended for human use (FDA warning letter, 2026-08-24; KPV was not among the products named).

No label or regulator lists who should avoid KPV because no product is approved. By general reasoning, the absence of reproductive toxicity data means nothing is known about exposure in pregnancy or breastfeeding, and competitive athletes face the WADA S0 rule described below.

Legal and regulatory status

Jurisdiction	Status
US FDA	Not approved; no USP monograph (FDA 2026)
US 503A compounding	Not on the Bulks List; nomination withdrawn; FDA staff proposed not adding it
US 503B	Not on the 503A Bulks List; no FDA-approved KPV product exists for outsourcing facilities to compound from (FDA)
WADA 2026	S0 non-approved substances, prohibited at all times (WADA list)
WADA 2027	S0, which from 2027-01-01 names “peptides” in general (USADA athlete advisory)
EU	No EMA-authorised product; no European Pharmacopoeia monograph

Dated events:

• Category 2 and withdrawal: KPV sat in FDA’s Category 2 of bulk substances that may pose significant safety risks. FDA’s page, current as of 2026-04-22, lists it under “nominated but withdrawn” and states that FDA “has not identified any human exposure data on drug products containing KPV administered via any route” (FDA Category 2 page).
• 2026-05-12 FDA evaluation: FDA reviewed KPV free base and KPV acetate on its own initiative for wound healing and inflammatory conditions, for topical cream and gel, and proposed not adding either to the 503A Bulks List (FDA briefing).
• 2026-07-23 advisory committee: The Pharmacy Compounding Advisory Committee discussed KPV alongside BPC-157, TB-500 and MOTS-c (FDA meeting page). Committee votes are advisory. FDA adds substances to the 503A Bulks List through notice-and-comment rulemaking (FDA 503A bulks page).
• WADA: The 2026 list bans at all times any pharmacological substance with “no current approval by any governmental regulatory health authority for human therapeutic use” that no other section covers (WADA 2026 Prohibited List). KPV has no such approval anywhere. On the 2027 List, in force from 2027-01-01, S0 also names “peptides” in general, a description that fits KPV directly (USADA athlete advisory).

Related peptides

• BPC-157: another unapproved peptide studied mainly in rodent gut and tissue models, reviewed by the same FDA committee on the same day.
• GHK-Cu: a tripeptide with skin and wound research, also withdrawn from FDA’s Category 2 list.
• Our overview of peptides banned in sport explains the WADA S0 and S2 classes.