Educational Reference · Research-Use-Only
KPV: Mechanism, Research, and Regulatory Status
A research-grade overview of KPV — what it is, how it works at the molecular level, what published studies have shown, and answers to the questions researchers ask most.
Last reviewed 2026-07-28
What is KPV?
KPV is the C-terminal tripeptide of alpha-melanocyte-stimulating hormone, a sequence it shares with the corresponding region of ACTH. Unlike the parent hormone, its anti-inflammatory activity in intestinal tissue does not depend on classical melanocortin receptor engagement: Dalmasso and colleagues showed that KPV enters intestinal epithelial and immune cells through PepT1, the proton-coupled oligopeptide transporter, and that transport is required for activity. Once intracellular, nanomolar KPV suppresses activation of the NF-kappaB and MAP kinase inflammatory signaling cascades, reducing downstream transcription of pro-inflammatory cytokines including TNF-alpha, IL-6 and IL-8.
Receptor-independence is supported genetically: KPV retained anti-inflammatory efficacy in MC1R-deficient mice, indicating the effect is at least partially independent of MC1R signaling. The dependence on PepT1 rather than a G-protein-coupled receptor was demonstrated causally by Viennois and colleagues, in which KPV suppressed colitis-associated tumorigenesis in wild-type mice but had no effect in PepT1-knockout mice. Tissue context appears to matter: in human bronchial epithelial cells an MC3R-dependent component to KPV's suppression of NF-kappaB-driven signaling has been reported, so the mechanism should not be assumed uniform across cell types.
Separately, alpha-MSH-derived peptides including this C-terminal sequence show direct antimicrobial activity against Staphylococcus aureus and Candida albicans, a property distinct from cytokine modulation. KPV does not reproduce the melanogenic activity of full-length alpha-MSH.
Research highlights
What published peer-reviewed research and preclinical studies have established about KPV:
- 01Nanomolar concentrations of KPV inhibited NF-kappaB and MAP kinase activation in intestinal epithelial and immune cell lines, and orally administered KPV reduced disease severity in two murine colitis models (Dalmasso 2008).
- 02KPV retained anti-inflammatory activity in MC1R-deficient mice, indicating the effect is at least partially independent of MC1R signaling (Kannengiesser 2008).
- 03KPV prevented tumor formation in a colitis-associated cancer model in wild-type mice but produced no benefit in PepT1-knockout mice, establishing PepT1 as required for the effect (Viennois 2016).
- 04Hyaluronic-acid-functionalized nanoparticles carrying KPV produced greater mucosal protection and TNF-alpha suppression than non-targeted delivery in murine colitis, indicating that free peptide delivery is a limiting factor (Xiao 2017).
- 05Alpha-MSH-derived peptides inhibited S. aureus colony formation and reduced C. albicans viability in vitro, a direct antimicrobial action distinct from cytokine signaling modulation (Cutuli 2000).
- 06No human clinical trial of KPV is registered on ClinicalTrials.gov and no published human interventional study was identified — the efficacy evidence base is entirely in vitro and rodent.
Frequently asked questions about KPV
What is KPV?+
KPV is a synthetic tripeptide with the sequence lysine-proline-valine, corresponding to residues 11-13 of alpha-melanocyte-stimulating hormone. It is used as a research reagent in studies of melanocortin-derived anti-inflammatory signaling and intestinal peptide transport, and is supplied for laboratory research use only.
How does KPV differ mechanistically from full-length alpha-MSH?+
Alpha-MSH acts as an agonist at melanocortin receptors and produces pigmentary effects. The KPV tripeptide, in intestinal models, is instead taken up intracellularly by the PepT1 oligopeptide transporter and inhibits NF-kappaB and MAPK signaling; its activity is retained in MC1R-deficient mice and abolished in PepT1-knockout mice. It does not reproduce the melanogenic activity of the parent hormone.
How does KPV relate to KdPT?+
KdPT (Lys-D-Pro-Thr) is a structurally related synthetic analog studied alongside KPV in the melanocortin literature. It is a different compound with a D-proline and a threonine substitution and should not be treated as interchangeable with KPV in experimental design or in citation of published results.
Is KPV stable in the gastrointestinal tract?+
Free KPV is a short peptide subject to luminal and brush-border peptidase activity, and published work has focused on formulation strategies to improve delivery. Nanoparticle and hydrogel delivery systems have produced substantially greater effects than free peptide in rodent colitis models, which is itself evidence that unformulated delivery is a limiting variable in study design.
What is the state of human evidence for KPV?+
There is none identified. No interventional human trial of KPV is registered on ClinicalTrials.gov and no published human study was located. All efficacy findings in the literature derive from cell culture and rodent models, and extrapolation beyond those models is unsupported.
References & sources
Every citation below was resolved against its primary source before publication — each PMID against the PubMed record and each DOI through doi.org. Follow any link to read the paper at the publisher rather than taking our summary on trust.
- [1]Dalmasso G, Charrier-Hisamuddin L, Nguyen HTT, Yan Y, Sitaraman S, Merlin D. PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation. Gastroenterology. 2008. PMID: 18061177 DOI: 10.1053/j.gastro.2007.10.026
- [2]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. PMID: 18092346 DOI: 10.1002/ibd.20334
- [3]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. PMID: 27458604 DOI: 10.1016/j.jcmgh.2016.01.006
- [4]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. PMID: 28143741 DOI: 10.1016/j.ymthe.2016.11.020
- [5]Brzoska T, Luger TA, Maaser C, Abels C, Böhm M. Alpha-melanocyte-stimulating hormone and related tripeptides: biochemistry, antiinflammatory and protective effects in vitro and in vivo, and future perspectives. Endocrine Reviews. 2008. PMID: 18612139 DOI: 10.1210/er.2007-0027
- [6]Cutuli M, Cristiani S, Lipton JM, Catania A. Antimicrobial effects of alpha-MSH peptides. Journal of Leukocyte Biology. 2000. PMID: 10670585 DOI: 10.1002/jlb.67.2.233
Where this data comes from
- —Citations & trial data: PubMed (NCBI, U.S. National Library of Medicine), Crossref and ClinicalTrials.gov.
- —Chemical identity: PubChem and UniProt. Where sources conflicted, the disputed value is omitted rather than guessed.
- —Regulatory status: U.S. FDA publications and, where applicable, the WADA Prohibited List. Compounding status changes frequently — verify against FDA directly before relying on it.
- —Purity, form and storage are handling and supplier conventions, not literature-derived values. Confirm against the lot-specific certificate of analysis.
Content last reviewed 2026-07-28. Compiled by Veridian Research from the primary literature. This page is an educational reference for laboratory researchers — it is not medical advice, and it describes no human use.
Regulatory status
KPV is not approved by the FDA, EMA, or any comparable regulatory authority for any indication in humans or animals. It has no marketing authorization and no human clinical trial data exist. Compounding status under the FDA 503A bulk drug substances framework has been subject to ongoing review and change; verify against FDA's currently published list rather than any secondary source. Supplied strictly as a research chemical for in vitro and non-clinical laboratory investigation — not for human consumption, therapeutic use, veterinary use, or administration to any living subject.
Research-Use-Only Material
Specifications and certificate of analysis
KPV is stocked as a research reagent. Analytical documentation — identity, purity and the lot-specific certificate of analysis — is published on the product record.
View specifications & COA →