KPV — the tripeptide Lys-Pro-Val: mechanism and research

KPV is three amino acids: lysine, proline and valine. That is what remains of the thirteen-amino-acid hormone α-MSH when everything but its tail is cut away. The fragment keeps the hormone’s anti-inflammatory action but does not darken the skin, which is why it has been studied as a separate molecule since the 1990s. Almost everything known about it comes from cell cultures and mouse models of intestinal inflammation.

This article organises that knowledge: where KPV came from, how it acts inside the cell, what animal studies showed and what is missing. No human studies have ever been published. We discuss separately the combination with BPC-157 that appears in catalogues, along with the legal and anti-doping status. We give no dosing information; the reason is set out in the FAQ section.

In our catalogue, the compounds discussed in this article are chemical reagents intended solely for laboratory research (Research Use Only). They are not medicinal products, dietary supplements or foods, and they are not intended for use in humans or animals. What this status means is explained in our material on the legal status of research reagents.

What KPV is

The hormone α-MSH is made from proopiomelanocortin, the same protein from which the body cuts ACTH. It has 13 amino acids and works through melanocortin receptors: it drives melanocytes to make pigment, and in the immune system it dampens inflammation. The last three amino acids of the chain, positions 11 to 13, are Lys-Pro-Val, written KPV in the one-letter code (Brzoska et al., 2008, PMID 18612139).

Researchers turned to this fragment for one reason. The full hormone is anti-inflammatory, yet it also darkens the skin, which gets in the way of using it as a medicine. The tripeptide kept the first property and lost the second. A 2008 review therefore singled it out as a candidate for anti-inflammatory therapy without the pigmentary effect (Brzoska et al., 2008). The same logic produced KdPT, a derivative with D-proline and threonine that corresponds to residues 193–195 of interleukin-1β.

The molecule is small: formula C₁₆H₃₀N₄O₄, mass 342.4 g/mol, CAS number 67727-97-3 (PubChem CID 125672). Catalogues list it as the free peptide or as an acetate salt. The US FDA points out that publications often fail to say which of the two forms was used (FDA briefing document, 2026).

Mechanism: how KPV acts in the cell

The first surprise concerns receptors. Full-length α-MSH acts through the melanocortin receptors MC1 to MC5. Activation of MC1 and MC3 limits the transfer of the NF-κB factor into the nucleus and, as a result, the production of inflammatory cytokines (Catania et al., 2004, PMID 15001661). The tripeptide itself behaves differently. In B16-F1 melanoma cells and RAW 264.7 macrophages it neither bound melanocortin receptors nor raised cAMP. Even so, it inhibited nitric oxide production in stimulated macrophages in a concentration-dependent way (Muceniece et al., 2003, PMID 12895656).

Animal work says the same thing. In mice with crystal-induced peritonitis, KPV reduced the influx of granulocytes, and an antagonist of the MC3 and MC4 receptors did not block the effect. A selective MC1 agonist produced no such effect at all, and the peptide also worked in mice with a non-functional MC1 receptor (Getting et al., 2003, PMID 12750433). The authors concluded that KPV is unlikely to act through melanocortin receptors and probably inhibits interleukin-1β functions. Schiöth’s group wrote plainly of “strong antiinflammatory activity without known cellular target” (Schiöth et al., 2006, PMID 17040213).

The question of how KPV gets inside the cell was answered by a group in Atlanta. The transporter PepT1 carries di- and tripeptides from digested food across the cell membrane. In a healthy colon it is almost absent, while in inflammatory bowel disease its expression rises. KPV turned out to be a PepT1 substrate and entered intestinal epithelial cells and T lymphocytes. Inside, at nanomolar concentrations, it inhibited NF-κB activation and MAPK signalling, which lowered cytokine release (Dalmasso et al., 2008, PMID 18061177).

For the reader, the most important sentence appears at the start of that paper: the mechanisms of action of KPV “still remain unknown”. The authors described the route into the cell and the outcome, a weaker inflammatory signal. They did not identify the protein the peptide binds once inside. A 2023 review of the melanocortin system in inflammatory bowel disease upholds that assessment (Gravina et al., 2023, PMID 37508552).

What the studies showed: mainly mouse models of colitis

The core of the KPV literature is a handful of mouse papers from 2008 to 2017. Two models of colitis were used: the chemical one with dextran sulfate sodium (DSS) and the one with trinitrobenzene sulfonic acid (TNBS). In both, KPV eased inflammation, and the effect depended on PepT1 (Dalmasso et al., 2008). A team from Münster confirmed this in the DSS model and in a transfer model, where inflammation is caused by transplanted lymphocytes. Mice treated with KPV regained body weight sooner and had smaller inflammatory infiltrates and lower myeloperoxidase activity in the colon (Kannengiesser et al., 2008, PMID 18092346).

The same paper added an important detail. In mice with a non-functional MC1 receptor, KPV kept every treated animal alive through the colitis. In the authors’ view, this points to an effect at least partly independent of that receptor (Kannengiesser et al., 2008). The following years brought work on delivering the peptide to the colon. KPV-loaded nanoparticles enclosed in an alginate and chitosan hydrogel eased inflammation in the DSS model. A concentration about 12,000 times lower than that of the free peptide in solution was enough (Laroui et al., 2010, PMID 19909746). Orally administered nanoparticles coated with hyaluronic acid targeted epithelial cells and macrophages (Xiao et al., 2017, PMID 28143741).

An interesting thread concerns cancer. PepT1 promotes colitis-associated colorectal cancer: mice overexpressing the transporter had larger tumours, and mice lacking it had smaller ones. In this model, KPV delivered through PepT1 limited both inflammation and tumour formation (Viennois et al., 2016, PMID 27458604). That is a mouse finding about mechanism, not about cancer prevention in humans.

Beyond the gut, KPV has been examined in skin and wound-healing models, where most cell types carry the MC1 receptor (Böhm and Luger, 2019, PMID 30661264). A newer paper from 2026 concerns metabolism. In 3T3-L1 preadipocytes, KPV inhibited differentiation into fat cells and limited the production of reactive oxygen species. In mice on a high-fat diet, it reduced weight gain (An et al., 2026, PMID 42585803). The common denominator of this entire literature is one thing: cell cultures and rodents.

What is missing: human studies

There are none. That sentence needs sources, so here they are, starting with the strongest. The ClinicalTrials.gov registry holds no trial of KPV (queried on 1 November 2026). While preparing its 2026 evaluation of KPV, FDA searched PubMed, Embase and its own adverse event database, FAERS. It found no clinical studies, no human exposure data, no case reports and no adverse event reports up to 3 December 2025. Nor did it find any publication in which a product containing KPV, compounded or otherwise, had been given to humans (FDA briefing document, 2026).

That evaluation arose from the 503A Bulks List, the list of substances US pharmacies may use in compounded medicines. KPV had been nominated as an ingredient of a preparation for “wound healing, inflammatory conditions (psoriasis, eczema, etc.)”. The nomination was withdrawn, but FDA assessed the peptide on its own initiative and concluded that the criteria weigh against adding it to the list. The agency stressed the complete absence of human data. It also observed that websites promote KPV alone and in combinations with BPC-157 and TB-500 for purposes that no human study supports (FDA briefing document, 2026).

FDA’s Pharmacy Compounding Advisory Committee voted on 23 July 2026 against the agency’s own reviewers. Eight members voted to add KPV to the list, six voted against and one abstained (McDermott Will & Schulte, 2026). The vote is advisory; the decision rests with FDA and had not been made at the time of publication. On FDA’s page about bulk substances for compounding that may present significant safety risks, KPV carries a note that the agency has identified no human exposure data of any kind. The agency adds that it does not know whether the peptide would cause harm if given to humans (FDA, 2026).

The absence of human data has practical consequences. Nobody knows whether the free peptide would survive digestion and reach the colon, given that in mice it was helped by nanocarriers and hydrogels. Nobody knows whether it triggers an immune response. A 2026 review lists KPV among peptides promoted in bodybuilding, including for recovery and anti-inflammatory effects. The authors conclude that clinical evidence for this whole group is limited (Coutinho et al., 2026, PMID 41880199). Our guide to peptides and SARMs studied for muscle building gives the wider picture.

KPV with BPC-157: what is known about the combination

In catalogues of peptides in capsules, KPV often comes paired with BPC-157, including in ours: ARG BPC-157 + KPV. The rationale is mechanistic. BPC-157 has been described in models of ulcers and tissue injury as cytoprotective and pro-angiogenic, and KPV as a brake on the inflammatory signal. The two therefore have different points of attack. Our article on BPC-157 capsules explains that line of reasoning.

Data on the combination are another matter. A PubMed query combining BPC-157 with KPV returns a single record. It is a review of peptides in pharmacy compounding rather than a study (Willis and Vu, 2026, PMID 42752426). No paper has tested whether the two peptides given together act differently from each one alone, either in a test tube or in animals. The complementarity of mechanisms is therefore an assumption, not a finding. The same applies to our article on BPC-157 and TB-500, which does not mention KPV, because there too the data on combinations end at assumptions.

A separate question concerns the oral form in the studies. The PepT1 transporter argues in its favour, since in rodents it carried the peptide into epithelial cells. In the 2008 paper, the mice received KPV in their drinking water (Dalmasso et al., 2008). The largest effect, however, came when the peptide was enclosed in nanoparticles targeted to the colon (Laroui et al., 2010; Xiao et al., 2017). For the free peptide without a carrier, no comparable data exist. The identity and purity of a batch are verified analytically, and how to read the resulting document is explained in our article on the certificate of analysis.

Regulatory status

European Union. No medicine containing KPV is authorised. The peptide is absent from the EU medicines data that EMA publishes under Article 57 (as of 9 October 2026). FDA’s own search of the European Medicines Agency found no authorised products either (FDA briefing document, 2026). Nor does KPV have authorisation as a food or food supplement ingredient in the EU. The reagent in our catalogue, KPV, is material for laboratory research.

United States. A Drugs@FDA search for KPV returns nothing (checked 1 November 2026), and FDA states that KPV is not a component of any approved drug. For peptides, the relevant US procedure is the 503A Bulks List described above. The nomination was withdrawn, the agency’s reviewers assessed the criteria as weighing against inclusion, and the advisory committee voted 8 to 6 in favour on 23 July 2026. No decision had been issued by 1 November 2026, and inclusion on that list would permit pharmacy compounding, not approve KPV as a drug.

Other countries. FDA found no monograph for KPV or its acetate in the United States Pharmacopeia–National Formulary. The European Pharmacopoeia (edition 11.8, 2025) and the Japanese Pharmacopoeia (18th edition) have none either (FDA briefing document, 2026). No registration as a medicine in any country is known. Sentences about a “natural gut peptide” on sales websites refer to mouse findings, not to a product that anyone has tested in humans.

Anti-doping note

KPV is not named on the WADA 2026 Prohibited List, which does not make it permitted in sport. Class S0 covers every pharmacological substance that no governmental regulatory health authority has approved as a medicine for human use, including compounds in preclinical development. KPV meets that condition, so it falls under class S0 and is prohibited at all times, both in and out of competition. The 2027 List, which takes effect on 1 January 2027, names “peptides” in class S0 explicitly (USADA, 2026). Athletes tested in the United States fall under the same List, because USADA is a signatory to the World Anti-Doping Code.

Some product pages state that KPV “is not on the list”. The sentence is true and misleading at once, because for unregistered compounds the prohibition follows from class S0, not from being named. Our guide to the WADA Prohibited List sets out the classification rules, including those for research compounds. The final word rests with WADA and the national anti-doping agencies.

Frequently asked questions

What is the KPV peptide?
The tripeptide Lys-Pro-Val, the last three amino acids of the hormone α-MSH. It keeps the hormone’s anti-inflammatory action seen in cell and animal models and has no effect on skin pigmentation.

Is KPV a natural remedy for the gut?
No. The findings come from mouse models of colitis, often with the peptide enclosed in nanoparticles. There are no studies in people with inflammatory bowel disease, and no registration of KPV as a medicine is known in any country.

Does KPV act through melanocortin receptors?
According to the available data, no. It did not bind those receptors in cell cultures, and in mice without a functional MC1 receptor it worked just the same. It enters cells through the PepT1 transporter, and the protein it binds inside remains unknown.

Is there evidence for combining KPV with BPC-157?
There are no studies that tested the two peptides together. The pairing in capsules rests on the assumption that different mechanisms complement each other, and that assumption has not been tested.

Why do we give no dosing information for KPV?
Because no clinical data exist for KPV from which any figure could be derived, and the reagent in our catalogue is not meant to be administered to anyone. The amounts used in mouse studies concern animals and nanocarriers, not people.

Is KPV prohibited in sport?
Yes. No approval as a medicine is known in any country, so it falls under class S0 of the WADA Prohibited List, prohibited at all times. The 2027 List names peptides in this class explicitly.

Summary

KPV is the C-terminal fragment of α-MSH that dampens the inflammatory signal without involving melanocortin receptors and without affecting pigmentation. It enters intestinal epithelial cells through the PepT1 transporter. The strongest data are mouse models of colitis from 2008 to 2017, in which the peptide eased inflammation, especially in nanocarriers targeted to the colon. No human studies exist, as FDA confirmed in 2026, and the agency’s advisory committee voted to add KPV to the 503A list against the view of its reviewers. The combination with BPC-157 has not been studied. As an unregistered compound, KPV falls under class S0 of the WADA List.

Product documentation

Reagent pages with batch documentation: KPV and the ARG BPC-157 + KPV blend. Compounds studied in the context of immunity and inflammation are collected in the category reagents in the context of immunity. Peptides with an anti-inflammatory and anxiolytic profile sit in the category reagents in the context of well-being. The identity and purity of each batch are confirmed by a certificate of analysis.

Bibliography

1. Brzoska T, Luger TA, Maaser C, et al. Alpha-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. Endocr Rev. 2008;29(5):581-602. doi:10.1210/er.2007-0027. PMID: 18612139
2. Catania A, Gatti S, Colombo G, et al. Targeting melanocortin receptors as a novel strategy to control inflammation. Pharmacol Rev. 2004;56(1):1-29. doi:10.1124/pr.56.1.1. PMID: 15001661
3. Getting SJ, Schiöth HB, Perretti M. Dissection of the anti-inflammatory effect of the core and C-terminal (KPV) alpha-melanocyte-stimulating hormone peptides. J Pharmacol Exp Ther. 2003;306(2):631-637. doi:10.1124/jpet.103.051623. PMID: 12750433
4. Muceniece R, Krigere L, Süli-Vargha H, et al. Effects of alpha-melanotropin C-terminal tripeptide analogues on macrophage NO production. Peptides. 2003;24(5):701-707. doi:10.1016/s0196-9781(03)00128-1. PMID: 12895656
5. Schiöth HB, Muceniece R, Mutule I, et al. New melanocortin 1 receptor binding motif based on the C-terminal sequence of alpha-melanocyte-stimulating hormone. Basic Clin Pharmacol Toxicol. 2006;99(4):287-293. doi:10.1111/j.1742-7843.2006.pto_459.x. PMID: 17040213
6. Dalmasso G, Charrier-Hisamuddin L, Nguyen HT, et al. PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation. Gastroenterology. 2008;134(1):166-178. doi:10.1053/j.gastro.2007.10.026. PMID: 18061177
7. Kannengiesser K, Maaser C, Heidemann J, et al. Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease. Inflamm Bowel Dis. 2008;14(3):324-331. doi:10.1002/ibd.20334. PMID: 18092346
8. Laroui H, Dalmasso G, Nguyen HT, et al. Drug-loaded nanoparticles targeted to the colon with polysaccharide hydrogel reduce colitis in a mouse model. Gastroenterology. 2010;138(3):843-853.e1-2. doi:10.1053/j.gastro.2009.11.003. PMID: 19909746
9. Xiao B, Xu Z, Viennois E, et al. Orally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis. Mol Ther. 2017;25(7):1628-1640. doi:10.1016/j.ymthe.2016.11.020. PMID: 28143741
10. Viennois E, Ingersoll SA, Ayyadurai S, et al. Critical role of PepT1 in promoting colitis-associated cancer and therapeutic benefits of the anti-inflammatory PepT1-mediated tripeptide KPV in a murine model. Cell Mol Gastroenterol Hepatol. 2016;2(3):340-357. doi:10.1016/j.jcmgh.2016.01.006. PMID: 27458604
11. Gravina AG, Pellegrino R, Durante T, et al. The Melanocortin System in Inflammatory Bowel Diseases: Insights into Its Mechanisms and Therapeutic Potentials. Cells. 2023;12(14):1889. doi:10.3390/cells12141889. PMID: 37508552
12. Böhm M, Luger T. Are melanocortin peptides future therapeutics for cutaneous wound healing? Exp Dermatol. 2019;28(3):219-224. doi:10.1111/exd.13887. PMID: 30661264
13. An SH, Park JY, Lee SJ. KPV attenuates adipogenesis and lipid metabolism through modulation of ROS-mediated AKT/mTORC1/PPARγ signaling. Tissue Cell. 2026;104(Pt 1):103837. doi:10.1016/j.tice.2026.103837. PMID: 42585803
14. Coutinho LFD, de Oliveira Neves LF, Camilo RP. A new era of doping? Use of peptide and peptide-analog drugs in recreational and professional sport and bodybuilding: a critical review. J Sports Med Phys Fitness. 2026;66(7):880-885. doi:10.23736/S0022-4707.26.17773-1. PMID: 41880199
15. Willis J, Vu N. Synthetic Peptides in Pharmacy Compounding: Analysis of PCAC Recommendations and Industry Safety Standards. Int J Pharm Compd. 2026;30(4):329-336. PMID: 42752426
16. U.S. Food and Drug Administration. FDA Briefing Document: KPV-Related Bulk Drug Substances (KPV (free base) and KPV acetate). Pharmacy Compounding Advisory Committee meeting, 23–24 July 2026. fda.gov (accessed 1 November 2026)
17. U.S. Food and Drug Administration. Certain bulk drug substances for use in compounding that may present significant safety risks. fda.gov (accessed 1 November 2026)
18. McDermott Will & Schulte. Bulk-list bound? PCAC backs majority of peptides in two-day public meeting. 27 July 2026. mcdermottlaw.com (accessed 1 November 2026)
19. National Center for Biotechnology Information. PubChem Compound Summary, CID 125672, Lys-Pro-Val (CAS 67727-97-3). pubchem.ncbi.nlm.nih.gov (accessed 1 November 2026)
20. ClinicalTrials.gov. Query “KPV”: 0 studies. clinicaltrials.gov (accessed 1 November 2026)
21. European Medicines Agency. Article 57 product data (data as of 9 October 2026): no entry for KPV. ema.europa.eu (accessed 1 November 2026)
22. World Anti-Doping Agency. The 2026 Prohibited List. wada-ama.org (accessed 1 November 2026)
23. U.S. Anti-Doping Agency. Athlete Advisory: What’s New on the 2027 WADA Prohibited List? (6 October 2026). usada.org (accessed 1 November 2026)