KPV is a tripeptide, lysine-proline-valine, cut from the end of α-melanocyte-stimulating hormone (α-MSH). Laboratory and animal studies have shown that it reduces inflammation, and it has been studied as a possible treatment for inflammatory bowel disease and skin inflammation[1].
All of that evidence comes from cells and animals. When the FDA reviewed KPV in 2026 for use in pharmacy compounding, it found no clinical studies, no case reports and no pharmacokinetic data in humans, and no toxicity studies in animals either[2]. This page sets out what is known about the molecule and where the evidence stops.
| Sequence | Lys-Pro-Val (K-P-V) |
|---|---|
| Origin | Residues 11–13 of α-MSH |
| Molecular weight | 342.43 Da (free tripeptide); 402.5 Da (acetate salt) |
| Studied for | Inflammatory bowel disease and skin inflammation, in cells and animals |
| Human studies | None found by the FDA in 2026 |
| Approved as a medicine | No; not a component of any FDA-approved drug |
Where it comes from
α-MSH is a 13-amino-acid hormone cut from a larger precursor protein, pro-opiomelanocortin. It is best known for stimulating pigmentation through melanocortin receptors, which recognise a short core motif in the middle of the chain, His-Phe-Arg-Trp[1][3]. α-MSH also damps inflammation. Studies that trimmed the hormone found that its last three amino acids, Lys-Pro-Val, kept anti-inflammatory and fever-lowering activity on their own; in rabbits with fever induced by interleukin-1, the antipyretic activity of α-MSH was traced to this C-terminal sequence[1].
Because KPV lacks the core motif, it is not expected to share the receptor-mediated pigmentary activity of α-MSH, and it is described as free of melanotropic effects[4]. That is part of its appeal: an anti-inflammatory fragment without the tanning effect.
Which KPV?
The name hides a chemical ambiguity. The FDA evaluated the free tripeptide H-Lys-Pro-Val-OH, molecular formula C16H30N4O4 and molecular weight 342.43, and its acetate salt; it treated the N-acetylated form as a separate substance outside its review[2]. A 2008 review of α-MSH-related peptides, by contrast, describes KPV as the N-acetylated and C-amidated tripeptide, molecular weight 383.49[1]. Several of the studies discussed below call their peptide simply "KPV" without stating its end groups[5][6][4].
Stereochemistry adds further variants. Versions with D-lysine, D-proline or D-valine, and the related tripeptide KdPT, in which D-proline replaces proline and threonine replaces valine, have been tested as well. Most studies used the all-L form[1]. The variants do not behave identically: KdPV, the D-proline isomer, had no fever-lowering activity in animals, yet it suppressed activation of the inflammatory transcription factor NF-κB in rat lung cells[1].
For anyone reading the literature, the practical point is that results for one form cannot be assumed for another. The FDA also concluded that neither the free tripeptide nor its acetate is well characterised physically and chemically, and that impurity data were missing. Even the nomination was inconsistent: its certificate of analysis named one substance in the title and gave the molecular formula of another, so it was unclear whether the free tripeptide or the acetate salt had been nominated[2].
How it seems to work
KPV does not appear to work through melanocortin receptors. In a 2003 mouse study of inflammation in the abdominal cavity, KPV reduced the influx of white blood cells, but a melanocortin-receptor blocker did not cancel this effect, KPV did not raise cAMP, the usual signal of these receptors, in macrophages, and it was still active in mice with a non-functional MC1 receptor. The authors concluded that KPV more likely acts by interfering with interleukin-1β[3].
A 2008 study proposed a route into cells. The transporter PepT1, which normally absorbs di- and tripeptides from food in the small intestine and appears in the colon during inflammatory bowel disease, carried KPV into intestinal and immune cells. Inside, nanomolar concentrations of KPV blocked NF-κB and MAP kinase signalling and reduced the release of inflammatory cytokines[5]. In uptake experiments with radiolabelled KPV, PepT1 transported nanomolar concentrations of the peptide, and the study linked this uptake to the anti-inflammatory effects seen at low concentrations[5]. A review noted that the dose-response of KPV in skin cells extended over six orders of magnitude, which cannot be explained by a simple interaction with a single receptor[1]. The mechanism is therefore not settled.
Studies in animals
| Study | Model | How KPV was given |
|---|---|---|
| Getting 2003 | Mouse peritonitis | Injection |
| Dalmasso 2008 | Mouse colitis (DSS, TNBS) | In drinking water |
| Kannengiesser 2008 | Mouse colitis (DSS, T-cell transfer) | 10 µg daily, into the abdomen |
| Laroui 2010 | Mouse colitis (DSS) | Nanoparticles in a gel, by mouth |
Sources: Getting et al.[3], Dalmasso et al.[5], Kannengiesser et al.[6], Laroui et al.[7].
In both colitis models of the Kannengiesser study, treated mice regained weight sooner and had less inflammation in the colon; KPV also worked in mice with a non-functional MC1 receptor[6]. The group that described PepT1 transport later packed KPV into nanoparticles inside an alginate-chitosan gel, given by mouth and designed to release them in the colon. In mice with colitis this gave a similar effect at a KPV concentration 12,000 times lower than that of KPV in free solution[7].
These are short experiments in induced colitis or peritonitis in mice. They show biological activity; they say nothing about dose, safety or benefit in people.
Getting through the skin
The use the FDA evaluated was a cream or gel at 0.1% for wound healing and inflammatory skin conditions such as psoriasis and eczema[2]. Whether KPV can reach its target from the skin surface is itself in doubt. In a 2017 laboratory study, under the conditions tested, passive permeation of KPV through excised human skin stayed below the detection limit of the assay. Pretreating the skin with microneedles allowed about 4.4 µg per cm² per hour through; a small electric current (iontophoresis) increased this about 8-fold, and the combination about 35-fold[4]. The FDA concluded that poor permeation could limit both the usefulness of topical KPV and its absorption into the body[2].
Human data and regulatory status
KPV is not part of any FDA-approved medicine. In its review for the list of substances that pharmacies may use for compounding (section 503A), the FDA found no human clinical studies, case reports or pharmacokinetic data, did not identify animal toxicity studies, and found insufficient data to rule out immune reactions. It concluded that the evidence weighs against adding either the free tripeptide or its acetate to the list[2].
KPV was discussed by the FDA's Pharmacy Compounding Advisory Committee on 23 July 2026, on the same day as BPC-157[8]. The committee's recommendations are advisory and do not themselves decide whether a substance is placed on the list; final minutes were not available on the FDA meeting page when this page was written. Nor should the FDA staff recommendation be mistaken for a final agency decision. Whatever the outcome, an advisory vote does not make KPV an approved medicine or establish its safety and effectiveness.
In short
- KPV is the tripeptide Lys-Pro-Val, the last three amino acids of α-MSH, which keeps the anti-inflammatory activity of the hormone without the melanocortin-receptor-mediated pigmentary activity of the parent hormone.
- The name is used for peptides with different terminal groups, including the free tripeptide and an N-acetylated, C-amidated form, as well as stereochemical variants that may behave differently.
- In cells and mice it reduced inflammation, including in colitis models; it does not appear to act through melanocortin receptors, and its mechanism is not settled.
- It barely crosses intact human skin in laboratory tests.
- In 2026 the FDA found no human studies and no toxicity studies, and FDA staff recommended against allowing it in pharmacy compounding.
References
- Brzoska T, Luger TA, Maaser C, Abels C, Böhm M (2008). α-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. Endocrine Reviews 29(5):581–602. DOI: 10.1210/er.2007-0027
- U.S. Food and Drug Administration (2026). Evaluation of KPV-related bulk drug substances (KPV (free base) and KPV acetate) for inclusion on the 503A bulk drug substances list. Briefing document for the Pharmacy Compounding Advisory Committee meeting of 23–24 July 2026. fda.gov (PDF)
- Getting SJ, Schiöth HB, Perretti M (2003). Dissection of the anti-inflammatory effect of the core and C-terminal (KPV) α-melanocyte-stimulating hormone peptides. Journal of Pharmacology and Experimental Therapeutics 306(2):631–637. DOI: 10.1124/jpet.103.051623
- Pawar K, Kolli CS, Rangari VK, Babu RJ (2017). Transdermal iontophoretic delivery of lysine-proline-valine (KPV) peptide across microporated human skin. Journal of Pharmaceutical Sciences 106(7):1814–1820. DOI: 10.1016/j.xphs.2017.03.017
- Dalmasso G, Charrier-Hisamuddin L, Nguyen HTT, Yan Y, Sitaraman S, Merlin D (2008). PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation. Gastroenterology 134(1):166–178. DOI: 10.1053/j.gastro.2007.10.026
- Kannengiesser K, Maaser C, Heidemann J, Luegering A, Ross M, Brzoska T, Böhm M, Luger TA, Domschke W, Kucharzik T (2008). Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease. Inflammatory Bowel Diseases 14(3):324–331. DOI: 10.1002/ibd.20334
- Laroui H, Dalmasso G, Nguyen HTT, Yan Y, Sitaraman SV, Merlin D (2010). Drug-loaded nanoparticles targeted to the colon with polysaccharide hydrogel reduce colitis in a mouse model. Gastroenterology 138(3):843–853. DOI: 10.1053/j.gastro.2009.11.003
- U.S. Food and Drug Administration. July 23–24, 2026: Meeting of the Pharmacy Compounding Advisory Committee. fda.gov