KPV

Origin and structure

KPV is a chain of three amino acids: lysine, proline and valine. They are the last three building blocks (positions 11 to 13) of alpha-melanocyte-stimulating hormone (alpha-MSH), a 13-amino-acid hormone cut from the precursor protein POMC. This end fragment was already thought to carry alpha-MSH's fever-lowering effect, and in 1989 Hiltz and Lipton showed that in mice it also inhibited chemically induced ear swelling, more strongly at higher doses.

Research-grade KPV is H-Lys-Pro-Val-OH (C16H30N4O4, 342.43 g/mol, CAS 67727-97-3), sold either unsalted (the 'free base') or as an acetate salt. Its last valine ends in a free acid group, so it is not exactly the natural fragment: in alpha-MSH that valine ends in an amide group. Related molecules appear in the literature under similar names, among them N-acetylated KPV, KPV dimers and KdPT (Lys-D-Pro-Thr). In its 2026 review the FDA noted that the free base and the acetate salt usually share one CAS number, that the nomination it reviewed mixed the two up, and that neither follows standard naming; it judged both not well characterised.

How it is thought to work

Full-length alpha-MSH works through melanocortin receptors: MC1R on pigment cells drives melanin production, while MC3R, MC4R and MC5R carry much of its anti-inflammatory effect. KPV does not appear to use them. In laboratory tests it did not displace alpha-MSH from its binding sites and did not raise cyclic AMP in cells carrying MC1R. In mice, a blocker of the MC3 and MC4 receptors did not stop its anti-inflammatory effect, and it still worked in mice with a non-functional MC1R.

The leading explanation comes from a 2008 study by Didier Merlin's group: KPV is carried into gut-lining cells and immune cells by PepT1, a transporter for small peptides that normally sits in the small intestine and is switched on in the colon during inflammatory bowel disease. In those cells, nanomolar concentrations of KPV blocked the NF-κB and MAP-kinase inflammation pathways and reduced the release of inflammatory cytokines. Other work points to interference with interleukin-1 beta. The FDA's 2026 review concluded that the molecular target is still unknown.

How KPV behaves in the human body has never been measured: there are no human pharmacokinetic data for any route. Through skin it barely passes on its own. On human donor skin, passive permeation stayed below the limit of detection; only microneedles or a weak electric current (iontophoresis), or both, carried measurable amounts through.

Is KPV approved?

No. No medicine containing KPV is authorised by the EMA or the FDA, and the FDA's 2026 review found no monograph for it in the European, US or Japanese pharmacopoeias. In the Netherlands it is not a registered medicine and may not be sold or promoted for human use; it is available only as research material, which is the basis our shop operates on.

In the United States the question is whether pharmacies may compound it. On 29 September 2023 the FDA placed KPV in Category 2 of its 503A bulk-substances list, the group flagged for significant safety risks, because it had found no human exposure data for any route. The nomination behind it, for a 0.1% cream or gel for wound healing and inflammatory conditions such as psoriasis and eczema, was later withdrawn. The FDA reviewed both forms anyway, on its own initiative: its staff evaluation, dated 12 May 2026, recommended against adding KPV to the list, citing poor characterisation, unknown use in compounding and the complete absence of human data. On 23 July 2026 the FDA's Pharmacy Compounding Advisory Committee voted 8 to 6, with one abstention, to recommend adding it. That vote is advice only, and no final FDA decision had been published when this page was checked in October 2026.

In sport KPV is not named on the WADA Prohibited List, but as a substance that no regulator has approved for human use it falls under category S0 and is prohibited at all times.

What the research shows

The evidence is small and entirely preclinical. The FDA searched the literature, ClinicalTrials.gov and its adverse-event databases (through December 2025) and found no clinical study, no case report and no adverse-event report for KPV; the nomination it reviewed cited nine papers, none of them in humans. The key gut studies come from two groups, Didier Merlin's in Atlanta and a team in Münster; a large share of the later work has tested new ways of packaging KPV, such as nanoparticles and hydrogels, for delivery in rodents. The main findings:

• Mouse ear swelling (Hiltz and Lipton, FASEB J 1989): KPV inhibited chemically induced ear swelling in a dose-related way, the first sign that the fragment is anti-inflammatory on its own.
• Mouse peritonitis (Getting et al., J Pharmacol Exp Ther 2003): injected KPV reduced the influx of white blood cells into the abdominal cavity, also in mice with a non-functional MC1R, and its effect was not blocked by a melanocortin-receptor antagonist.
• Colitis (Dalmasso et al., Gastroenterology 2008): KPV in the drinking water reduced DSS- and TNBS-induced colitis in mice and lowered inflammatory cytokine expression in the colon.
• Colitis (Kannengiesser et al., Inflamm Bowel Dis 2008): in DSS colitis and T-cell transfer colitis, treated mice regained weight faster and showed less inflammation; in DSS colitis in mice with a non-functional MC1R, all KPV-treated animals survived.
• Targeted delivery (Laroui et al., Gastroenterology 2010): loaded into colon-targeted nanoparticles, KPV protected mice against DSS colitis at a concentration 12,000 times lower than free KPV in solution, with a similar effect.
• Wound healing: the FDA's review cites positive results in rodent wound-healing models and notes that researchers have called for clinical studies; none has been done.
• Closest human data: a randomised phase IIa trial in mild-to-moderate ulcerative colitis tested KdPT, a different tripeptide, as an add-on to standard treatment (Kucharzik et al., Inflamm Bowel Dis 2017). It was well tolerated and met its primary endpoint only after additional analyses, against a very high placebo response. It says nothing direct about KPV.
• Safety testing: according to the FDA, no acute or repeat-dose toxicity, genotoxicity, reproductive or carcinogenicity studies of KPV exist, and whether it provokes an immune response in humans is unknown.

KPV versus alpha-MSH and Melanotan

KPV is often grouped with the melanocortin peptides, but it behaves differently. Alpha-MSH and its synthetic analogues act on melanocortin receptors, and activating MC1R on pigment cells is what darkens the skin. Afamelanotide (Melanotan I), a modified full-length alpha-MSH, has been authorised in the EU as Scenesse since 22 December 2014, under exceptional circumstances, to prevent phototoxicity in adults with erythropoietic protoporphyria. Melanotan II is a melanocortin-receptor agonist as well.

KPV lacks the His-Phe-Arg-Trp core that these molecules use to bind the receptors, and the cell and animal data suggest it does not activate them, so a tanning effect is not expected from its pharmacology. That has never been checked in people. What KPV shares with alpha-MSH is an anti-inflammatory signal in animal models; it shares none of the human data behind afamelanotide.

Frequently asked questions

Is KPV legal in the Netherlands?

KPV is not a registered medicine in the Netherlands or anywhere else in the EU, so it may not be sold or promoted for human use. It can be bought and sold as research material, which is the basis our shop works on.

Is KPV FDA-approved?

No. The only US movement is the compounding review: FDA staff advised against putting KPV on the 503A list, an advisory committee voted 8 to 6 in July 2026 to recommend it anyway, and the FDA has not yet decided. Even a positive decision would only allow pharmacy compounding; it would not make KPV an approved drug.

Does KPV work in humans?

Nobody knows, because it has never been tested in people. The mouse colitis results come from two independent groups and point the same way, but mouse colitis models are an imperfect guide to patients, and the only randomised trial in this area tested a different tripeptide, KdPT.

Is KPV banned in sport?

Yes. It is not named on the WADA list, but as an unapproved pharmacological substance it falls under category S0, prohibited in and out of competition. The Dopingautoriteit applies the same list in the Netherlands.

Does KPV tan the skin like Melanotan?

It is not expected to. Tanning comes from activating MC1R on pigment cells, and in cell and animal studies KPV neither bound nor activated that receptor. Melanotan I and II are melanocortin-receptor agonists that do. No human study has looked at KPV and skin colour.

Is KPV absorbed when swallowed or put on the skin?

There are no human data for either route. In mice, KPV in drinking water reduced colitis, probably because the PepT1 transporter takes it up in the gut; whether that happens in people has never been measured. On human donor skin, KPV did not get through without microneedles or iontophoresis.

Storage and handling

Store according to product-label instructions and batch handling notes. Lyophilized research peptides are commonly kept dry, protected from light, and handled with clean laboratory technique.

References

Checked against these sources on 28 October 2026.

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