KPV: the alpha-MSH derived tripeptide in published research

In short: KPV is the tripeptide lysine-proline-valine, the last three amino acids (positions 11 to 13) of alpha-melanocyte-stimulating hormone (alpha-MSH). Its published record is cell and animal research, much of it in mouse colitis models, and no human trials were found. The TGA’s April 2026 peptide advisory does not name KPV among its examples.

This review sets out what KPV is, how it relates to the melanocortin peptide family, which mechanisms laboratories have tested and where the evidence stops. Each study is labelled by type, using the categories in how to read a peptide study. A tripeptide is a chain of three amino acids. KPV is one of the four components of the KLOW peptide blend, alongside the copper peptide covered in our GHK-Cu research review.

Key facts

Property	Value
Name and synonyms	KPV; Lys-Pro-Val; L-lysyl-L-prolyl-L-valine; alpha-MSH(11-13); ACTH(11-13) 1
Sequence and length	Lys-Pro-Val, 3 amino acid residues; residues 148 to 150 of human pro-opiomelanocortin 2
Molecular formula	C16H30N4O4 (free acid) 1
Molecular weight	342.43 g/mol 1
CAS number	67727-97-3 1
PubChem CID	125672 1
Compound class	Linear tripeptide; melanocortin-derived peptide fragment
Evidence base	Cell and animal studies. No registered or published human trials found 3, 4
WADA status	Not named in the 2026 WADA Prohibited List 5
TGA status	Not among the five peptides the TGA’s 13 April 2026 safety advisory names as examples of unapproved peptide products 6

What is KPV?

KPV is a tripeptide with the sequence lysine-proline-valine, identical to the C-terminal end of the hormone alpha-MSH.

Alpha-MSH is a 13-residue peptide, SYSMEHFRWGKPV in one-letter code. It is cut from a larger precursor protein, pro-opiomelanocortin (POMC), which also yields adrenocorticotropic hormone (ACTH), other melanocyte-stimulating hormones and beta-endorphin. In the UniProt record for human POMC, alpha-MSH occupies residues 138 to 150, so KPV corresponds to residues 148 to 150 2. Alpha-MSH acts through the melanocortin receptors, a family of five receptors named MC1R to MC5R 7.

Early KPV research focused on fever. In a 1984 rabbit study, Richards and Lipton tested whether the 11 to 13 sequence of alpha-MSH accounted for the parent hormone’s effect on fever. KPV reduced fever in rabbits made febrile with leukocytic pyrogen, but with lower potency than alpha-MSH, which the authors read as a sign that other parts of the molecule were needed for the full effect 8. In a 1989 mouse study, Hiltz and Lipton reported that alpha-MSH(11-13) inhibited ear swelling induced by the irritant picryl chloride, compared with saline 9.

A 2008 review by Brzoska and colleagues describes how KPV came to be studied as an alternative to alpha-MSH: it was reported to keep anti-inflammatory activity in experimental models while lacking the pigmentary action of the parent hormone 10.

How is KPV structured?

KPV is a short linear peptide with lysine at the N-terminus, proline in the middle and valine at the C-terminus.

Each residue contributes something different. Lysine carries a side-chain amino group that is positively charged at neutral pH. Proline’s side chain loops back onto its own backbone nitrogen, forming a ring that restricts how the chain can bend. Valine has a branched, water-repelling side chain.

Free acid and amide forms. In the parent hormone, the final valine is a valine amide: UniProt annotates position 150 of POMC as amidated 2. The PubChem record for KPV (CID 125672) is the free acid, with a carboxylic acid group at the C-terminus 1. Several studies used an acetylated, amidated version, Ac-Lys-Pro-Val-NH2 11, 7. Amidation and N-terminal acetylation change the molecular formula and weight, so they are part of a peptide’s identity.

Stereochemistry. Amino acids other than glycine exist as mirror-image L- and D-forms, and proteins made in cells use the L-forms. In a 1991 mouse study, Hiltz, Catania and Lipton tested Ac-KPV-NH2 with single residues switched to their D-forms in the ear-swelling model. Switching proline to D-proline abolished the activity measured, switching lysine to D-lysine left it similar, and switching valine to D-valine increased it about four-fold 11.

Conformation. In a 2001 computational study, Chavatte and colleagues used molecular dynamics simulations to map the shapes Ac-Lys-Pro-Val-NH2 can adopt, then used the lowest-energy shapes as templates for designing non-peptide analogues 7.

Illustration: a short three-unit peptide chain. It does not show the exact structure of KPV.

What mechanisms have researchers studied?

No single receptor for KPV has been established in the studies reviewed here. Published work points to effects that do not depend on melanocortin receptors, uptake by a peptide transporter, and changes in NF-kappaB signalling.

Melanocortin receptors. In a 2001 cell study in RAW 264.7 macrophage-like cells, Mandrika and colleagues reported that alpha-MSH(11-13) inhibited nitric oxide production and the nuclear translocation of NF-kappaB, a transcription factor that switches on inflammatory genes. Unlike alpha-MSH, it did not compete for binding at MC1 receptor sites and did not raise cyclic AMP (cAMP), the second messenger linked in that study to MC1 receptor activation 12.

In a 2003 mouse and cell study, Getting and colleagues reported that KPV reduced neutrophil accumulation in crystal-induced peritonitis, that the effect was not blocked by an MC3 and MC4 receptor antagonist, and that it was also seen in mice with a non-functional MC1 receptor. In culture, KPV did not raise cAMP or inhibit macrophage activation. The authors concluded that KPV was unlikely to act through melanocortin receptors and more likely acted by inhibiting IL-1beta functions 13. Kannengiesser and colleagues also reported effects in MC1R-deficient mice and described them as at least partly independent of MC1R 14. Schiöth and colleagues described the tripeptide as having no known cellular target, and reported that two tyrosine-extended analogues bound selectively to the MC1 receptor 15.

Peptide transporter uptake. PepT1 is a membrane transporter that carries di- and tripeptides into cells. In a 2008 cell and mouse study, Dalmasso and colleagues described PepT1 as normally expressed in the small intestine and induced in the colon during inflammatory bowel disease. They reported that KPV entered human intestinal epithelial cells and immune cells through PepT1, inhibited NF-kappaB and MAP kinase inflammatory signalling and reduced pro-inflammatory cytokine secretion 16.

Nuclear import. In a 2012 study in immortalised human bronchial epithelial cells, Land reported that KPV inhibited NF-kappaB signalling and the secretion of the chemokines IL-8 and eotaxin. The effect was associated with KPV entering the nucleus and with reduced nuclear import of the NF-kappaB subunit p65RelA. Competition assays suggested an interaction at the site where the transport protein importin-alpha3 binds p65RelA 17.

Antimicrobial activity. In a 2000 laboratory study, Cutuli and colleagues reported that alpha-MSH and KPV inhibited colony formation by Staphylococcus aureus and reduced the viability and germ tube formation of the yeast Candida albicans. The authors linked these effects partly to increased cAMP in the microbes 18.

What does the published research include?

The published research on KPV is cell and animal work, and most recent animal studies use mouse models of colitis (inflammation of the colon).

A Europe PMC title search on 28 September 2026 returned fewer than 30 PubMed-indexed papers with KPV or one of its alternative names in the title 4. Dextran sulfate sodium (DSS) and trinitrobenzene sulfonic acid (TNBS) are chemicals used to induce colitis in rodents. Findings in the table are in each study’s own terms and apply only to the model tested.

Study	Study type	Model	What was measured	Reported finding
Mandrika 2001	Cell study	RAW 264.7 macrophage-like cells stimulated with LPS and interferon-gamma	Nitric oxide; NF-kappaB translocation; MC1 receptor binding; cAMP	Inhibited nitric oxide production and NF-kappaB translocation; no MC1 receptor binding or cAMP rise
Getting 2003	Mouse and cell study	Crystal-induced and IL-1beta-induced peritonitis, including MC1R non-functional mice; macrophages	Neutrophil accumulation; macrophage activation; cAMP	Reduced neutrophil accumulation, also in MC1R non-functional mice; no effect on macrophage activation or cAMP in culture
Dalmasso 2008	Cell and mouse study	Human intestinal epithelial cells and T cells; DSS and TNBS colitis in mice	NF-kappaB and MAP kinase activation; PepT1 uptake; colitis histology; cytokine RNA	Uptake through PepT1; inhibited inflammatory signalling; reduced colitis incidence and pro-inflammatory cytokine expression
Kannengiesser 2008	Mouse study	DSS colitis; T cell transfer colitis; MC1R-deficient mice	Body weight; histology; myeloperoxidase activity	Earlier recovery and body weight regain, fewer inflammatory infiltrates, lower myeloperoxidase; all treated MC1R-deficient mice survived DSS colitis
Laroui 2010	Cell and mouse study	Caco2-BBE intestinal cells; DSS colitis in mice; KPV in nanoparticles within a polysaccharide hydrogel	Inflammatory responses; histology	Reduced inflammatory responses in cells; mice protected on inflammatory and histological measures compared with DSS alone
Schaible 2013	Mouse study	Controlled cortical impact brain injury	Lesion volume; microglial activation; neuronal apoptosis; TNF-alpha and IL-1beta	Smaller secondary lesion volume, less microglial activation and neuronal apoptosis; TNF-alpha and IL-1beta not reduced
Viennois 2016	Mouse study	Colitis-associated cancer model in wild-type and PepT1-knockout mice	Tumour number and size; intestinal inflammation	KPV prevented carcinogenesis in wild-type mice, with no such effect in PepT1-knockout mice
Xiao 2017	Cell and mouse study	Colonic epithelial cells and macrophages; mouse ulcerative colitis model; hyaluronic acid-coated nanoparticles	Uptake by target cells; mucosal damage; TNF-alpha	Coated nanoparticles reached target cells and showed greater prevention of mucosal damage and lower TNF-alpha than uncoated KPV nanoparticles

Illustration: cell-culture work, one of the two main settings for published KPV research.

What are the limits of the evidence?

All of the KPV evidence reviewed here is preclinical, and no human trials were found.

• Human data. Searches of ClinicalTrials.gov and Europe PMC on 28 September 2026 found no registered or published human trials of KPV 3, 4. Our explainer on why most peptide research is preclinical covers what that means for interpretation.
• Concentration of authorship. Four of the colitis studies in the table share a senior author, Didier Merlin 16, 19, 21, 22. Lipton is an author on the early fever, ear-swelling and antimicrobial studies 8, 9, 18.
• Carriers. Two colitis studies delivered KPV inside nanoparticles held in hydrogels 19, 22. Their results describe the peptide and its carrier together, not KPV alone.
• Open mechanism. Receptor studies found no melanocortin receptor target 12, 13, while transporter and nuclear-import studies describe routes inside the cell 16, 17. How these fit together is not settled in the studies reviewed.
• Analogues. Results for acetylated, amidated or D-amino acid versions 11, or for tyrosine-extended analogues 15, do not automatically apply to KPV itself.
• Model limits. DSS, TNBS and crystal-induced peritonitis are chemically induced rodent models. They reproduce selected features of a human disease, not the disease itself.

What is KPV’s regulatory and anti-doping status in Australia?

KPV is not among the peptides the TGA names in its April 2026 advisory, and it is not named on the 2026 WADA Prohibited List.

The TGA’s safety advisory of 13 April 2026 names BPC-157, GHK-Cu, TB-500, retatrutide and CJC-1295 as examples of unapproved peptide products, meaning goods not included in the Australian Register of Therapeutic Goods (ARTG). It says these products have not been evaluated by the TGA for safety, quality or effectiveness. KPV is not among the named examples, which the advisory presents as examples rather than a complete list 6.

KPV is not named in the 2026 WADA Prohibited List, in effect from 1 January 2026 5. The list’s section S0 (non-approved substances) is not limited to named examples: it covers any pharmacological substance not addressed by other sections and with no current approval by any governmental regulatory health authority for human therapeutic use. Check the current WADA Prohibited List and Sport Integrity Australia, and see our anti-doping status table for research peptides.

How is KPV characterised in the lab?

KPV is characterised with the standard tools for synthetic peptides: HPLC for purity and mass spectrometry for identity.

• Purity and stability. In a 2015 analytical study, Pawar and colleagues developed and validated a stability-indicating reversed-phase HPLC method for KPV, meaning one that separates the intact peptide from its degradation products. It used a C18 column with water and acetonitrile mobile phases containing trifluoroacetic acid, and was validated for accuracy, precision, linearity and limits of detection and quantitation. Under acid, alkali and hydrogen peroxide stress, KPV formed lys-pro-diketopiperazine, a cyclic two-residue product, as its major degradation product, identified by mass spectrometry 23. See what an HPLC purity percentage does and does not tell you.
• Identity. Mass spectrometry checks that the measured mass matches Lys-Pro-Val (C16H30N4O4, 342.43 g/mol for the free acid) 1. An acetylated or amidated form would give a different mass. See how mass spectrometry confirms peptide identity.
• Salt form. PubChem’s synonym list for KPV includes acetate salt entries 1, a reminder that synthetic peptides can be supplied as salts with a counter-ion. Our explainer on acetate and TFA salts covers why the counter-ion matters, and our guide to reading a peptide certificate of analysis shows where it appears on a report.

Frequently asked questions

What does KPV stand for?

KPV is written in one-letter amino acid code: K for lysine, P for proline and V for valine. The peptide is also called Lys-Pro-Val, lysyl-prolyl-valine and alpha-MSH(11-13), because it matches positions 11 to 13 of alpha-melanocyte-stimulating hormone 2. PubChem lists it as CID 125672, with the molecular formula C16H30N4O4 1.

Is KPV the same as alpha-MSH?

No. Alpha-MSH has 13 residues and KPV only the last three 2. In a cell study, alpha-MSH competed for MC1 receptor binding and raised cAMP, while alpha-MSH(11-13) did neither 12. A 2003 mouse and cell study concluded that KPV was unlikely to act through melanocortin receptors 13. Our glossary entry on parent proteins explains how fragments relate to the proteins they come from.

Has KPV been tested in humans?

Searches of ClinicalTrials.gov and Europe PMC on 28 September 2026 found no registered or published human trials of KPV 3, 4. The published record consists of cell studies and animal studies, mainly in mice. Our guide to how to read a peptide study explains why findings from these models cannot be read as results in people.

Is KPV named in the TGA’s peptide advisory?

The TGA’s safety advisory of 13 April 2026 names BPC-157, GHK-Cu, TB-500, retatrutide and CJC-1295 as examples of unapproved peptide products, meaning goods not included in the Australian Register of Therapeutic Goods. KPV is not among the named examples, which the advisory presents as examples rather than a complete list 6.

Is KPV on the WADA Prohibited List?

KPV is not named in the 2026 WADA Prohibited List 5. Section S0 of the list (non-approved substances) covers any pharmacological substance not addressed elsewhere in the list and with no current approval by any governmental regulatory health authority for human therapeutic use. Check the current list, Sport Integrity Australia and our anti-doping status table.

How is KPV analysed in the lab?

Purity is measured by HPLC and identity by mass spectrometry. A 2015 analytical study validated a reversed-phase HPLC method that separated KPV from its degradation products, and identified lys-pro-diketopiperazine as the main product under acid, alkali and peroxide stress 23. Our explainer on HPLC purity covers what the resulting purity figure means.

References

1. PubChem. Msh (11-13), Lys-Pro-Val (CID 125672). https://pubchem.ncbi.nlm.nih.gov/compound/125672. Accessed 28 September 2026. [compound database]
2. UniProt. Pro-opiomelanocortin, human (P01189). https://www.uniprot.org/uniprotkb/P01189/entry. Accessed 28 September 2026. [protein database]
3. ClinicalTrials.gov. Search for the term KPV. https://clinicaltrials.gov/search?term=KPV. Accessed 28 September 2026. [trial registry]
4. Europe PMC. Title search for KPV, Lys-Pro-Val, lysine-proline-valine and alpha-MSH(11-13), PubMed-indexed records; and search for KPV records tagged as clinical trials. https://europepmc.org/. Accessed 28 September 2026. [literature search]
5. World Anti-Doping Agency. World Anti-Doping Code International Standard: Prohibited List 2026. https://www.wada-ama.org/en/prohibited-list. Accessed 28 September 2026. [anti-doping regulator]
6. Therapeutic Goods Administration. Understanding your responsibilities when importing, compounding and supplying unapproved peptide products (safety advisory, 13 April 2026). https://www.tga.gov.au/safety/safety-monitoring-and-information/safety-alerts/understanding-your-responsibilities-when-importing-compounding-and-supplying-unapproved-peptide-products. Accessed 28 September 2026. [regulator]
7. Chavatte P, Yous S, Lesieur D, et al. Conformational analysis of tripeptide Ac-Lys-Pro-Val-NH2, COOH-terminal sequence of alpha-MSH. Journal of Pharmacy and Pharmacology. 2001;53(7):949-953. doi:10.1211/0022357011776360. PMID: 11480545. [computational modelling study]
8. Richards DB, Lipton JM. Effect of alpha-MSH 11-13 (lysine-proline-valine) on fever in the rabbit. Peptides. 1984;5(4):815-817. doi:10.1016/0196-9781(84)90027-5. PMID: 6333677. [rabbit study]
9. Hiltz ME, Lipton JM. Antiinflammatory activity of a COOH-terminal fragment of the neuropeptide alpha-MSH. FASEB Journal. 1989;3(11):2282-2284. doi:10.1096/fasebj.3.11.2550304. PMID: 2550304. [mouse study]
10. 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. Endocrine Reviews. 2008;29(5):581-602. doi:10.1210/er.2007-0027. PMID: 18612139. [narrative review]
11. Hiltz ME, Catania A, Lipton JM. Anti-inflammatory activity of alpha-MSH(11-13) analogs: influences of alteration in stereochemistry. Peptides. 1991;12(4):767-771. doi:10.1016/0196-9781(91)90131-8. PMID: 1788140. [mouse study]
12. Mandrika I, Muceniece R, Wikberg JE. Effects of melanocortin peptides on lipopolysaccharide/interferon-gamma-induced NF-kappaB DNA binding and nitric oxide production in macrophage-like RAW 264.7 cells: evidence for dual mechanisms of action. Biochemical Pharmacology. 2001;61(5):613-621. doi:10.1016/s0006-2952(00)00583-9. PMID: 11239505. [cell study]
13. Getting SJ, Schiöth HB, Perretti M. Dissection of the anti-inflammatory effect of the core and C-terminal (KPV) alpha-melanocyte-stimulating hormone peptides. Journal of Pharmacology and Experimental Therapeutics. 2003;306(2):631-637. doi:10.1124/jpet.103.051623. PMID: 12750433. [mouse and cell study]
14. Kannengiesser K, Maaser C, Heidemann J, et al. Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease. Inflammatory Bowel Diseases. 2008;14(3):324-331. doi:10.1002/ibd.20334. PMID: 18092346. [mouse study]
15. 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 & Clinical Pharmacology & Toxicology. 2006;99(4):287-293. doi:10.1111/j.1742-7843.2006.pto_459.x. PMID: 17040213. [receptor-binding and cell study]
16. 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. PMCID: PMC2431115. [cell and mouse study]
17. Land SC. Inhibition of cellular and systemic inflammation cues in human bronchial epithelial cells by melanocortin-related peptides: mechanism of KPV action and a role for MC3R agonists. International Journal of Physiology, Pathophysiology and Pharmacology. 2012;4(2):59-73. PMID: 22837805. PMCID: PMC3403564. [cell study]
18. Cutuli M, Cristiani S, Lipton JM, et al. Antimicrobial effects of alpha-MSH peptides. Journal of Leukocyte Biology. 2000;67(2):233-239. doi:10.1002/jlb.67.2.233. PMID: 10670585. [microbiology and cell study]
19. 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):843-53.e1-2. doi:10.1053/j.gastro.2009.11.003. PMID: 19909746. [cell and mouse study]
20. Schaible EV, Steinsträßer A, Jahn-Eimermacher A, et al. Single administration of tripeptide α-MSH(11-13) attenuates brain damage by reduced inflammation and apoptosis after experimental traumatic brain injury in mice. PLoS One. 2013;8(8):e71056. doi:10.1371/journal.pone.0071056. PMID: 23940690. PMCID: PMC3733710. [mouse study]
21. 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. Cellular and Molecular Gastroenterology and Hepatology. 2016;2(3):340-357. doi:10.1016/j.jcmgh.2016.01.006. PMID: 27458604. PMCID: PMC4957955. [mouse study]
22. Xiao B, Xu Z, Viennois E, et al. Orally targeted delivery of tripeptide KPV via hyaluronic acid-functionalized nanoparticles efficiently alleviates ulcerative colitis. Molecular Therapy. 2017;25(7):1628-1640. doi:10.1016/j.ymthe.2016.11.020. PMID: 28143741. PMCID: PMC5498804. [cell and mouse study]
23. Pawar KR, Mulabagal V, Smith F, et al. Stability-indicating HPLC assay for lysine-proline-valine (KPV) in aqueous solutions and skin homogenates. Biomedical Chromatography. 2015;29(5):716-721. doi:10.1002/bmc.3347. PMID: 25298219. [analytical method study]