Research-use-only context. This article summarizes published third-party scientific literature and laboratory practice. It is not medical advice, not a therapeutic or performance claim, and not a usage guide. US Prime Peptides products are supplied strictly for in vitro laboratory research and are not for human or veterinary use.
This article explains what KPV is, where the three residues come from within alpha-melanocyte-stimulating hormone, and what the peer-reviewed literature reports for the tripeptide in cultured human cells, in mouse and rat models, and in rabbit cornea. It also covers the open question of how a peptide that lacks the melanocortin receptor pharmacophore produces its measured effects, why KPV is unstable in solution, why it appears in the KLOW blend, and what has not been established.
KPV is the C-terminal tripeptide of alpha-MSH
KPV is L-lysyl-L-prolyl-L-valine, residues 11 to 13 of the thirteen-residue hormone alpha-MSH, whose full sequence is Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val with an acetylated N-terminus and an amidated C-terminus. The free tripeptide has the formula C16H30N4O4, a molecular weight of about 342.4 daltons, PubChem CID 125672, and CAS number 67727-97-3. In the literature it is written as alpha-MSH(11-13), MSH 11-13, or simply KPV; a variant with D-valine, KP-D-V, and a disulfide-linked dimer, (CKPV)2, also appear.
The reason the fragment attracted attention is structural. Alpha-MSH binds the five melanocortin receptors through its central His-Phe-Arg-Trp motif, residues 6 to 9. KPV contains none of that motif. Brzoska and colleagues, in a 2010 Advances in Experimental Medicine and Biology chapter, put the point directly: KPV lacks the entire sequence required for binding to any known melanocortin receptor yet retains most of the full hormone's measured effects on inflammatory signaling, while showing no pigmentary activity. That separation of two activities of the parent hormone is the central fact about the molecule and the reason it is studied independently rather than as a weak alpha-MSH substitute. Readers who want the receptor side of the family can start with the overviews of PT-141 and Melanotan I and II, both of which do carry the His-Phe-Arg-Trp core.
The founding experiments: mouse ear swelling and human cells
Hiltz and Lipton established the fragment's activity in a 1989 FASEB Journal paper. Working from earlier evidence that alpha-MSH reduced fever and histamine-induced vascular permeability, and that the C-terminal tripeptide carried the antipyretic message, they applied picryl chloride to the ears of mice to induce contact-type swelling and compared graded amounts of alpha-MSH(11-13) against saline and a corticosteroid. The tripeptide reduced ear swelling in a concentration-related manner. This single mouse experiment is the origin of nearly every later claim about KPV.
The in vitro work that followed used human cells. Cutuli, Cristiani, Lipton, and Catania, in a 2000 Journal of Leukocyte Biology paper, reported that alpha-MSH and KPV reduced colony formation by Staphylococcus aureus and reduced viability and germ-tube formation by Candida albicans over a wide concentration range, that cyclic AMP rose in peptide-exposed yeast, and that an adenylyl cyclase inhibitor partly reversed the killing. The same year Barcellini and colleagues, also in the Journal of Leukocyte Biology, showed in the chronically HIV-1-infected promonocytic U1 cell line and in acutely infected monocyte-derived macrophages that both peptides reduced p24 antigen release, and that KPV inhibited activation of the transcription factor NF-kappaB. Catania and colleagues summarized this cluster of work in a 2000 Annals of the New York Academy of Sciences paper framing alpha-MSH and KPV as candidate components of innate host defense.
Gatti and colleagues extended the work to the dimer in a 2006 Journal of Surgical Research paper. In human peripheral blood mononuclear cells stimulated with lipopolysaccharide, (CKPV)2 lowered TNF-alpha output and was more potent than monomeric KPV; in rats challenged with lipopolysaccharide, circulating TNF-alpha one hour later was markedly lower in animals that also received the dimer. Catania's group had already solved the dimer's solution structure by proton NMR in a 2005 Journal of Peptide Research paper, describing an extended backbone with a beta-turn-like element.
Signaling without a melanocortin receptor: what cell studies found
How KPV signals is unresolved, and the two most careful studies point in different directions. Elliott and colleagues, in a 2004 Journal of Investigative Dermatology paper, looked for the classic melanocortin response, a rise in cyclic AMP, in HaCaT and normal human keratinocytes exposed to alpha-MSH, KPV, KP-D-V, or ACTH fragments across femtomolar to 100-nanomolar concentrations. They found none. What they did find was a rapid intracellular calcium transient in response to all of the peptides, but only when an adenosine agonist that suppresses the cAMP pathway was present. In Chinese hamster ovary cells stably expressing the MC1 receptor, alpha-MSH and the KPV peptides both raised intracellular calcium, which the authors read as evidence that the tripeptides can engage MC1R-linked calcium signaling even though they cannot raise cAMP.
Dalmasso and colleagues, in a 2008 Gastroenterology paper, proposed a receptor-independent route. They showed that KPV competes with a radiolabeled substrate of the di- and tripeptide transporter PepT1 in the human intestinal epithelial lines Caco2-BBE and HT29-Cl.19A and in Jurkat T cells, measured the kinetics of tritiated KPV uptake, and reported that nanomolar KPV inhibited NF-kappaB and MAP-kinase signaling and lowered pro-inflammatory cytokine output in those cells. In their model the tripeptide is carried into the cytosol by PepT1 and acts inside the cell. Zeng and colleagues built on this in a 2017 ACS Applied Materials and Interfaces paper by conjugating KPV to a fluorescent dicyanomethylene-pyran dye and showing accumulation in the cytoplasm and nucleus of PepT1-overexpressing Caco-2 cells.
Luger and colleagues, in a 2003 Annals of the New York Academy of Sciences paper, reported that KPV bound MC1R and modulated antigen-presenting cell function, and that in a mouse contact-hypersensitivity model both alpha-MSH and KPV inhibited sensitization and elicitation and induced hapten-specific tolerance. Taken together, the literature supports at least two mechanisms, transporter-mediated intracellular action and a non-canonical MC1R-linked calcium signal, and does not settle which dominates in any given tissue.
Mouse and rat colitis models, and a rabbit cornea study
The largest body of in vivo work is in chemically induced intestinal inflammation in rodents. Dalmasso's 2008 study supplied KPV in drinking water to mice given dextran sulfate sodium or trinitrobenzene sulfonic acid and reported lower colitis incidence, better histology, and lower colonic mRNA for pro-inflammatory cytokines than in water-only controls. Kannengiesser and colleagues, in a 2008 Inflammatory Bowel Diseases paper, tested KPV in DSS colitis and in CD45RB-high T-cell transfer colitis and measured earlier recovery of body mass, fewer inflammatory infiltrates on histology, and lower colonic myeloperoxidase activity. Critically, they repeated the DSS experiment in MC1Re/e mice, which carry a non-functional MC1 receptor, and the tripeptide's effect persisted, which argues that MC1R is not required for the colonic finding.
Later papers are delivery-science studies that use KPV as the payload. Xiao and colleagues, in a 2017 Mol Ther paper, loaded KPV into hyaluronic-acid-coated polymeric nanoparticles of about 272 nanometers, showed uptake by colonic epithelial cells and macrophages, and reported less mucosal damage and lower TNF-alpha in DSS-colitis mice given the particles in a chitosan-alginate hydrogel than in mice given uncoated particles. Sun and colleagues, in a 2021 ACS Biomaterials Science and Engineering paper, embedded KPV in a self-cross-linked thiolated polyglutamic acid hydrogel for a rat TNBS model and, notably for a laboratory reader, reported that free KPV in solution lost measurable activity after two hours at 37 degrees Celsius, whereas the hydrogel preserved it.
One study sits outside the gut. Bonfiglio and colleagues, in a 2006 Experimental Eye Research paper, removed the corneal epithelium of rabbits by mechanical abrasion, applied KPV drops or vehicle, and measured the remaining fluorescein-stained defect every twelve hours. The defect closed faster in KPV-exposed eyes, the effect was reproduced by a nitric oxide donor, and a nitric oxide synthase inhibitor blocked it, placing nitric oxide in the pathway in that model.
What is not established
No controlled human trial of monomeric KPV has been published. The dimer (CKPV)2 was described in 2006 as under clinical investigation for antimicrobial use, but no efficacy trial results for it have appeared in the peer-reviewed literature since. KPV is not an approved drug in the United States or elsewhere, and neither is any KPV-containing product. The mechanism remains divided between the PepT1-uptake model and the non-canonical receptor model, and almost all of the in vivo data come from a single class of rodent models, chemically induced colitis, plus one rabbit cornea study. The human cell data are consistent across several laboratories but are limited to cytokine, NF-kappaB, and viral-expression readouts in immortalized or primary leukocyte and epithelial lines.
A second gap is stability. The 2021 hydrogel paper's observation that KPV solution loses activity within hours at body temperature is consistent with a short unprotected peptide being cleared by peptidases, and it means that any experiment with KPV in aqueous medium needs a freshly prepared solution and a stability control. The general principles are covered in the peptide storage and stability guide.
Why KPV appears in the KLOW blend, and what a certificate should show
KPV is sold on its own and as one component of the four-part KLOW blend, which lists GHK-Cu, BPC-157, TB-500, and KPV at labeled masses of 50, 10, 10, and 10 milligrams. The blend exists because the four peptides are studied in overlapping tissue-repair and inflammation models; it does not exist because any paper has tested the four together. No published study has examined the combination, so the blend's behavior in any assay is an open research question rather than a documented property. US Prime Peptides lists KPV 10 mg and KLOW 50/10/10/10 mg with lot-matched certificates posted before purchase.
| Certificate line | What it should show for KPV | Why it matters |
|---|---|---|
| Identity (LC-MS) | Observed [M+H]+ near 343.2, matching C16H30N4O4 | Confirms the sequence mass; cannot distinguish L-Val from D-Val |
| Purity (HPLC) | Area percent of the main peak, 99 percent or higher | A 342-dalton tripeptide elutes early; deletion impurities are dipeptides |
| Net peptide content | Percent of vial mass that is peptide, not counter-ion or water | Three basic sites bind acetate or TFA; content can be well below 100 percent |
| Blend components | Separate identity and content for each of four peptides | KPV and GHK-Cu may co-elute; the method must resolve them |
| Copper (ICP-MS) | Reported for KLOW because of the GHK-Cu component | Distinguishes the complex from free GHK |
Because mass spectrometry cannot tell KPV from KP-D-V, a laboratory that needs the all-L form should ask for the synthesis record or a chiral method. For reading the rest of the panel, see net peptide content versus purity and reading a blend certificate.
Frequently Asked Questions
What is KPV peptide?
KPV is the tripeptide lysine-proline-valine, the last three residues of the hormone alpha-MSH. It lacks the His-Phe-Arg-Trp motif that binds melanocortin receptors, so it does not produce pigmentation signaling, yet it reproduces much of the parent hormone's effect on inflammatory signaling in cell and rodent studies.
How does KPV work if it does not bind melanocortin receptors?
Two mechanisms are proposed. A 2008 Gastroenterology study showed that the peptide transporter PepT1 carries KPV into intestinal epithelial and immune cells, where it inhibits NF-kappaB. A 2004 keratinocyte study found a calcium signal, but no cAMP rise, through MC1R-expressing cells. The literature has not settled which route dominates.
Has KPV been tested in humans?
No controlled human trial of KPV has been published. Human data are limited to cultured human cells, including keratinocytes, intestinal epithelial lines, peripheral blood mononuclear cells, and HIV-infected monocytic cells. KPV is not an approved drug anywhere.
Is KPV stable in solution?
Not for long. A 2021 hydrogel study reported that free KPV in aqueous solution lost measurable activity after two hours at 37 degrees Celsius, which is expected for an unprotected tripeptide. Laboratory work with KPV should use freshly reconstituted solutions and include a stability control.
Citations
- Hiltz ME, Lipton JM. Antiinflammatory activity of a COOH-terminal fragment of the neuropeptide alpha-MSH. FASEB J. 1989;3:2282-2284. PMID 2550304
- Cutuli M, Cristiani S, Lipton JM, Catania A. Antimicrobial effects of alpha-MSH peptides. J Leukoc Biol. 2000;67:233-239. PMID 10670585
- Barcellini W, Colombo G, La Maestra L, et al. Alpha-melanocyte-stimulating hormone peptides inhibit HIV-1 expression in chronically infected promonocytic U1 cells and in acutely infected monocytes. J Leukoc Biol. 2000;68:693-699. PMID 11073109
- Catania A, Cutuli M, Garofalo L, et al. The neuropeptide alpha-MSH in host defense. Ann N Y Acad Sci. 2000;917:227-231. PMID 11268348
- Luger TA, Scholzen TE, Brzoska T, Böhm M. New insights into the functions of alpha-MSH and related peptides in the immune system. Ann N Y Acad Sci. 2003;994:133-140. PMID 12851308
- Elliott RJ, Szabo M, Wagner MJ, et al. alpha-Melanocyte-stimulating hormone, MSH 11-13 KPV and adrenocorticotropic hormone signalling in human keratinocyte cells. J Invest Dermatol. 2004;122:1010-1019. PMID 15102092
- Catania A, Grieco P, Randazzo A, et al. Three-dimensional structure of the alpha-MSH-derived candidacidal peptide [Ac-CKPV]2. J Pept Res. 2005;66:19-26. PMID 15946192
- Gatti S, Carlin A, Sordi A, et al. Inhibitory effects of the peptide (CKPV)2 on endotoxin-induced host reactions. J Surg Res. 2006;131:209-214. PMID 16413580
- Bonfiglio V, Camillieri G, Avitabile T, et al. Effects of the COOH-terminal tripeptide alpha-MSH(11-13) on corneal epithelial wound healing: role of nitric oxide. Exp Eye Res. 2006;83:1366-1372. PMID 16965771
- Dalmasso G, Charrier-Hisamuddin L, Nguyen HT, et al. PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation. Gastroenterology. 2008;134:166-178. PMID 18061177
- 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;14:324-331. PMID 18092346
- Brzoska T, Böhm M, Lügering A, et al. Terminal signal: anti-inflammatory effects of alpha-melanocyte-stimulating hormone related peptides beyond the pharmacophore. Adv Exp Med Biol. 2010;681:107-116. PMID 21222263
- 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;25:1628-1640. PMID 28143741
- Zeng M, Shao A, Li H, et al. Peptide receptor-targeted fluorescent probe: visualization and discrimination between chronic and acute ulcerative colitis. ACS Appl Mater Interfaces. 2017;9:13029-13036. PMID 28349696
- Sun J, Xue P, Liu J, et al. Self-cross-linked hydrogel of cysteamine-grafted gamma-polyglutamic acid stabilized tripeptide KPV for alleviating TNBS-induced ulcerative colitis in rats. ACS Biomater Sci Eng. 2021;7:4859-4869. PMID 34547895
This article is for laboratory research reference only. US Prime Peptides products are supplied strictly for in vitro research. Not for human consumption.
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