KPV (Lys-Pro-Val) is the C-terminal tripeptide of alpha-MSH. A research guide to how it enters cells through PepT1, how it blocks NF-κB nuclear import, what the colitis and inflammation models showed, the unresolved melanocortin-receptor question, and practical notes for the lab.
KPV (Lys-Pro-Val) is the C-terminal tripeptide of alpha-melanocyte-stimulating hormone (α-MSH), residues 11 to 13 of that 13-amino-acid hormone. Reviews of the α-MSH literature attribute most of the hormone's anti-inflammatory activity to this short fragment [1], and note that KPV keeps that activity without α-MSH's effect on pigmentation [3]. That combination has made KPV a useful tool for studying inflammation apart from melanocortin biology. This guide covers where KPV comes from, the mechanisms that have been worked out, what the animal models showed, and how researchers study it.
α-MSH is a tridecapeptide cut from the precursor proopiomelanocortin, with the sequence SYSMEHFRWGKPV [1][6]. It has well-documented anti-inflammatory effects in animal models of dermatitis, vasculitis, fibrosis, ocular, gastrointestinal, brain and airway inflammation, and arthritis, many of which are mediated through melanocortin receptors [3]. The central His-Phe-Arg-Trp sequence is the core melanocortin motif [7]. KPV lies outside that core.
The idea that the C-terminal fragment might carry activity of its own came from fever research. Hiltz and Lipton noted that the tripeptide was believed to carry α-MSH's antipyretic message, and in 1989 they tested α-MSH(11-13) in a mouse model of picryl chloride-induced ear swelling, a contact hypersensitivity reaction [5]. The tripeptide inhibited swelling in a graded fashion, and the comparison arms included saline and a corticosteroid. That paper is the starting point for KPV as an anti-inflammatory research tool.
This is the first question most researchers ask, and the evidence mostly says no. Getting and colleagues compared KPV with α-MSH, the core HFRW peptide, the MC3/MC4 agonist MTII, and a selective MC1 agonist in a mouse model of crystal-induced peritonitis [7]. KPV reduced neutrophil accumulation, and the MC3/MC4 antagonist SHU9119 did not block that effect. In vitro, KPV neither inhibited macrophage release of KC and IL-1β nor raised cAMP, whereas α-MSH and MTII inhibited that release and MTII raised cAMP. KPV remained active in IL-1β-induced peritonitis and in mice with a nonfunctional MC1 receptor. The authors concluded that KPV is unlikely to act through melanocortin receptors and more likely interferes with IL-1β functions. In colitis, Kannengiesser and colleagues likewise found KPV effective in MC1R-deficient mice and described its effects as at least partly independent of MC1R [4].
If KPV does not signal through a surface receptor, how does it act? Dalmasso and colleagues found that it is carried into cells by PepT1, the intestinal di- and tripeptide transporter [2]. PepT1 is normally expressed in the small intestine and is induced in the colon during inflammatory bowel disease. In human intestinal epithelial cell lines (Caco2-BBE and HT29-Cl.19A) and in Jurkat T cells stimulated with pro-inflammatory cytokines, nanomolar KPV inhibited NF-κB and MAP kinase signaling and reduced pro-inflammatory cytokine secretion. Uptake studies with tritium-labeled KPV and competition against a radiolabeled PepT1 substrate supported transport through PepT1.
A 2016 mouse study made the transporter dependence clear in vivo [10]. In a model of colitis-associated cancer, KPV prevented tumor development in wild-type mice but had none of that effect in PepT1-knockout mice.
Once inside the cell, KPV appears to act at the step where NF-κB enters the nucleus. In immortalized human bronchial epithelial cells stimulated with TNF-α or respiratory syncytial virus, Land found that KPV inhibited NF-κB reporter activity, MMP-9 activity and secretion of the chemokines IL-8 and eotaxin in a concentration-dependent way [8]. KPV itself was imported into the nucleus, stabilized IκBα, and reduced nuclear translocation of a YFP-tagged p65 (RelA) subunit. Competition experiments pointed to an interaction at the site where importin-α3 binds p65. In the same cells, γ-MSH also suppressed NF-κB, but only through the melanocortin receptor MC3R, which makes a useful contrast with KPV's receptor-independent route.
Cutuli and colleagues reported that α-MSH and KPV inhibited colony formation by Staphylococcus aureus and reduced the viability and germ tube formation of Candida albicans, over a wide range of concentrations reaching down to the picomolar [6]. They proposed a mechanism involving increased cAMP in the microbe, partly reversed by an adenylyl cyclase inhibitor, rather than membrane disruption. The peptides did not impair killing of these organisms by human neutrophils; if anything they enhanced it. These data cover two organisms in one study, so the antimicrobial activity is best regarded as a lead rather than a settled property.
Intestinal inflammation is where KPV has been studied most. Kannengiesser and colleagues tested it in two established mouse models, dextran sodium sulfate (DSS) colitis and CD45RBhi T-cell transfer colitis [4]. In DSS colitis, KPV-exposed mice recovered earlier and regained more body weight, with fewer inflammatory infiltrates on histology and lower myeloperoxidase activity in colonic tissue. Transfer colitis gave similar results. In MC1R-deficient mice given DSS, all KPV-exposed animals survived. Dalmasso's group, which added KPV to the drinking water as part of its study design, reported reduced DSS- and TNBS-induced colitis and lower pro-inflammatory cytokine expression [2].
Later work examined targeted delivery. Xiao and colleagues loaded KPV into hyaluronic acid-functionalized polymer nanoparticles of about 272 nm, which delivered the peptide to colonic epithelial cells and macrophages [9]. Given orally to mice in a chitosan/alginate hydrogel, these particles gave stronger protection against mucosal damage and greater TNF-α reduction in a colitis model than the same system without hyaluronic acid targeting.
Two related molecules are often confused with KPV. α-MSH itself acts largely through melanocortin receptors and affects pigmentation [3], so results with the full hormone do not carry over directly to the tripeptide. KdPT, a tripeptide derived from residues 193 to 195 of IL-1β and containing a D-amino acid, is a separate anti-inflammatory peptide discussed in the same reviews [1][3]. When reading the literature, check which of the three a study actually used.
In cells, standard readouts include NF-κB luciferase reporters, Western blotting of signaling proteins, qRT-PCR and ELISA for cytokines [2], and live imaging of fluorescently tagged p65 with IκBα stability measurements [8]. Uptake is studied with labeled KPV and competition against known PepT1 substrates [2]. In vivo, DSS, TNBS and T-cell transfer colitis are scored by body weight, histology and myeloperoxidase activity [2][4]. Peritonitis models use neutrophil counts [7], and contact hypersensitivity models use ear swelling [5]. Useful mechanistic controls include MC1R-deficient mice and melanocortin receptor antagonists such as SHU9119 [4][7], and PepT1-knockout mice [10]. Antimicrobial activity is assessed by colony formation and, for Candida, germ tube formation [6].
KPV is a small, hydrophilic tripeptide (342.43 Da) supplied as a white lyophilized powder. Store it at -20°C, sealed and dry. Let the vial reach room temperature before opening, dissolve it in sterile water or buffer, and keep working solutions in single-use aliquots. Because KPV uptake depends on PepT1 [2], other di- and tripeptides in a culture medium could in principle compete for transport. Keep media consistent between experimental arms.
Confirm identity by mass spectrometry and purity by HPLC. Northbridge Research Labs sends every batch for independent third-party testing, and published certificates are on our COA page. For example, KPV 10mg lot KPV001, tested in August 2026, showed an HPLC purity of 99.16%.
Note: KPV is sold strictly for laboratory research use only. It is not for human or veterinary use.
Studied compound
KPV (Lysine-Proline-Valine)
The same material this research covers — 99%+ purity, independently tested, with the certificate for each batch published online.
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