What Is KPV Peptide? The α-MSH Tripeptide Explained

KPV is a tripeptide, Lys-Pro-Val, that forms the C-terminal end (residues 11–13) of alpha-melanocyte-stimulating hormone (α-MSH). Researchers have studied it as the smallest α-MSH fragment that keeps anti-inflammatory activity in experimental models, and as a peptide that cells take up through the intestinal transporter PepT1.

For laboratory research use only. The compounds discussed are not approved for human or veterinary use and are not drugs, foods or cosmetics. This article summarises published research and is not medical advice.

Key points

Sequence Lys-Pro-Val; C₁₆H₃₀N₄O₄, 342.4 g/mol.
Derived from the C-terminus of α-MSH (residues 11–13).
Transported into intestinal and immune cells by PepT1.
Inhibited NF-κB and MAPK signalling in cell models and reduced chemically induced colitis in mice.
Most evidence is preclinical; no approved KPV medicine exists.

Quick facts

Property	Value
Sequence	Lys-Pro-Val (KPV)
Formula / mass	C₁₆H₃₀N₄O₄, 342.4 g/mol (PubChem CID 125672)
Parent peptide	α-MSH (13 residues), C-terminal tripeptide
Charge at neutral pH	Net positive (lysine)
Cell uptake	PepT1 di/tripeptide transporter
Status	Research compound

Lot data for our KPV research peptide (10 mg vials) are published with each batch.

From α-MSH to KPV

α-MSH is a 13-residue melanocortin peptide with well-documented anti-inflammatory effects in experimental systems. A 1998 review described how these effects are mediated, including inhibition of inflammatory mediators, and noted that the C-terminal tripeptide KPV retained activity in several models (Lipton et al., 1998). That observation prompted later work on KPV as a minimal fragment.

How KPV has been studied

Model	Finding	Study
Human intestinal epithelial cells (Caco2-BBE, HT29-Cl.19A) and T cells (Jurkat)	Nanomolar KPV inhibited NF-κB and MAP kinase activation and reduced pro-inflammatory cytokine secretion; the effect depended on PepT1	Dalmasso et al., 2008
Mouse DSS- and TNBS-induced colitis	KPV in drinking water reduced colitis incidence and pro-inflammatory cytokine expression	Dalmasso et al., 2008
Mouse colitis, nanoparticle delivery	Hyaluronic-acid-functionalised nanoparticles were used to target KPV to the inflamed colon	Xiao et al., 2017
Human keratinocytes and MC1R-transfected cells	No cyclic AMP rise in keratinocytes; KPV raised intracellular calcium in MC1R-expressing cells	Elliott et al., 2004

PepT1: why transport matters

PepT1 is a proton-coupled transporter for di- and tripeptides. It is normally expressed in the small intestine and is induced in the colon during inflammatory bowel disease. Dalmasso and colleagues showed that KPV competes for PepT1, that radiolabelled KPV is taken up with defined kinetics, and that KPV’s anti-inflammatory effect in their cell models required the transporter (Dalmasso et al., 2008). This suggests KPV may act inside cells, which differs from how α-MSH acts through melanocortin receptors on the cell surface.

Receptor question

Whether KPV acts through melanocortin receptors is not settled. Elliott and colleagues found no cyclic AMP increase in keratinocytes exposed to α-MSH, KPV or ACTH peptides, but did see rapid calcium signals under certain conditions, and KPV elevated calcium in cells transfected with MC1R (Elliott et al., 2004). Together with the PepT1 data, this suggests that more than one mechanism may operate depending on cell type.

KPV in blends

KPV is one of four components of the KLOW blend (with GHK-Cu, TB-500 and BPC-157). Its small mass (342 Da) and positive charge distinguish it from the other components by MS and HPLC. See what is the KLOW blend?

Handling in the lab

Store lyophilized powder at −20 °C, sealed and dark.
Readily water-soluble; reconstitute with bacteriostatic or sterile water (method).
Keep solutions at 2–8 °C; avoid repeated freeze–thaw (storage guide).
Calculate concentrations with the peptide reconstitution calculator.

Open questions

What is KPV’s intracellular target after PepT1 uptake? The signalling effects are documented, but the binding partner is not.
How stable is KPV in plasma and tissue? We did not find a formal pharmacokinetic study of the free tripeptide.
Do the colitis findings in mice translate to other models of inflammation? Most published data come from gut and skin systems, and independent replication remains limited.

Related research

Frequently asked questions

What is KPV peptide?

KPV is a tripeptide, Lys-Pro-Val, corresponding to amino acids 11–13 at the C-terminus of alpha-melanocyte-stimulating hormone (α-MSH). It is studied as the smallest fragment of α-MSH that retains anti-inflammatory activity in experimental models.

What does KPV do in research models?

In human intestinal epithelial and immune cells, nanomolar KPV inhibited NF-κB and MAP kinase signalling and reduced pro-inflammatory cytokine secretion. In mice, oral KPV reduced the incidence of chemically induced colitis.

How does KPV enter cells?

Via PepT1, a di- and tripeptide transporter expressed in the small intestine and induced in the colon during inflammation. KPV uptake and its anti-inflammatory effect in cell models depended on PepT1.

Does KPV act on melanocortin receptors?

Evidence is mixed. In one study, KPV raised intracellular calcium in cells transfected with the melanocortin-1 receptor, but did not raise cyclic AMP in keratinocytes. Its effects in gut cells have been attributed to intracellular action after PepT1 uptake.

What is KPV's molecular weight?

About 342.4 g/mol (C16H30N4O4) for the free tripeptide.

References

Dalmasso G, et al. PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation. Gastroenterology. 2008. PMID: 18061177 https://pubmed.ncbi.nlm.nih.gov/18061177/
Elliott RJ, et al. alpha-Melanocyte-stimulating hormone, MSH 11-13 KPV and adrenocorticotropic hormone signalling in human keratinocyte cells. J Invest Dermatol. 2004. PMID: 15102092 https://pubmed.ncbi.nlm.nih.gov/15102092/
Lipton JM, et al. Mechanisms of antiinflammatory action of the neuroimmunomodulatory peptide alpha-MSH. Ann N Y Acad Sci. 1998. PMID: 9629264 https://pubmed.ncbi.nlm.nih.gov/9629264/
Xiao B, et al. Orally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis. Mol Ther. 2017. PMID: 28143741 https://pubmed.ncbi.nlm.nih.gov/28143741/
PubChem Compound Summary for CID 125672, Lys-Pro-Val. National Center for Biotechnology Information. https://pubchem.ncbi.nlm.nih.gov/compound/125672