KPV is a three-amino-acid peptide, lysine-proline-valine, that matches the last three residues of α-melanocyte-stimulating hormone (α-MSH). It is small enough to be carried into cells by peptide transporters, and it lacks the receptor-activating core of the parent hormone, which makes it a useful probe for anti-inflammatory signaling that does not depend on classic melanocortin pharmacology.
Most published KPV work concerns intestinal inflammation in mouse models and cultured epithelial cells, with newer studies on drug-delivery carriers. Below is an outline of where the peptide comes from, the uptake and signaling findings, the main experimental models, and the gaps that remain.
At a glance
- Class: Tripeptide; C-terminal fragment of α-MSH (residues 11–13)
- Origin: Identified through structure-activity studies of α-MSH’s anti-inflammatory activity, reviewed by Brzoska and colleagues (Brzoska et al., 2008)
- Structure: Lys-Pro-Val; C16H30N4O4; 342.43 g/mol; CAS 67727-97-3
- Main research areas: intestinal epithelial biology, mouse colitis models, NF-κB signaling, oral and mucosal delivery systems
- Regulatory status: Not FDA approved for any use
Structure and origin
α-MSH is a 13-residue peptide cleaved from pro-opiomelanocortin (POMC). Its central His-Phe-Arg-Trp segment is the pharmacophore that activates melanocortin receptors and drives the hormone’s pigment-related effects. Researchers studying α-MSH’s anti-inflammatory actions noticed that the C-terminal end, Lys-Pro-Val at positions 11–13, retained anti-inflammatory activity in several assays despite lacking that core, a line of work summarized in two reviews (Brzoska et al., 2008; Brzoska et al., 2010).
In α-MSH, the terminal valine is amidated. The identifiers listed above (C16H30N4O4, 342.43 g/mol) correspond to the free-acid tripeptide, and readers comparing papers should check which form a given study used. Lysine provides a positively charged side chain, proline introduces a fixed kink, and valine adds a small hydrophobic end. At about 342 g/mol, KPV is in the size range recognized by di- and tripeptide transporters, a property central to the gut research.
Mechanism: what the research shows
The key mechanistic study came from Dalmasso and colleagues in 2008. Working with intestinal epithelial cell lines, they showed that KPV is taken up through PepT1, the proton-coupled di/tripeptide transporter expressed on intestinal epithelium. Once inside, KPV was associated with reduced activation of NF-κB and MAP kinase pathways and lower secretion of pro-inflammatory cytokines in response to inflammatory stimuli. In their experiments, these effects depended on PepT1-mediated transport (Dalmasso et al., 2008).
A second question was whether KPV acts through melanocortin receptors at all. Kannengiesser and colleagues tested KPV in mice carrying a nonfunctional melanocortin-1 receptor and still observed activity in colitis models, suggesting that at least part of the effect is independent of MC1R (Kannengiesser et al., 2008). Together, these studies support a model in which KPV works intracellularly after transporter uptake rather than by binding a surface receptor, although the exact intracellular target has not been defined.
Key areas of study
Intestinal epithelial cells
Cultured colonic epithelial cell lines are the basic in-vitro system. Readouts include PepT1-dependent uptake, NF-κB nuclear translocation, MAP kinase phosphorylation and cytokine release (Dalmasso et al., 2008).
Mouse colitis models
Dextran sulfate sodium (DSS) colitis, a chemically induced model of epithelial injury, is the most common in-vivo system. KPV has also been studied in T-cell transfer colitis, an immune-driven model in which naive T cells are transferred into immunodeficient mice. Endpoints in these studies included weight change, histological inflammation scores and tissue inflammatory markers (Kannengiesser et al., 2008; Dalmasso et al., 2008).
Targeted delivery systems
Because KPV is small and rapidly cleared, several groups have built carriers to keep it at inflamed tissue. Xiao and colleagues loaded KPV into hyaluronic acid-functionalized nanoparticles, which target CD44 on colonic epithelial cells and macrophages, and delivered them orally in a hydrogel to mice with DSS colitis (Xiao et al., 2017). This work is as much about formulation science as about the peptide itself.
Melanocortin fragment pharmacology
KPV is also used alongside related tripeptides, such as KdPT (Lys-D-Pro-Thr), to compare anti-inflammatory activity across α-MSH fragments in skin and immune-cell models (Brzoska et al., 2008).
What the evidence does not show
- The literature is preclinical: cell lines and mouse models. There are no published controlled trials of KPV in humans.
- The core mechanistic findings rest on a relatively small number of laboratories, and the intracellular target remains unidentified.
- Colitis models capture parts of intestinal inflammation but not the full complexity of human disease.
- Studies differ in peptide form (free acid or amide), route and formulation, which complicates direct comparison.
- KPV is not an approved drug for any indication.
Regulatory status
KPV is not approved by the FDA for any use. Rogue Compounds sells it as a research reagent only.
Handling and storage in the lab
Lyophilized KPV should be kept sealed and refrigerated at 2–8°C (36–46°F), protected from light.
Sourcing and documentation
Rogue Compounds has KPV made in small batches. Every vial carries a batch number and a QR code that opens the independent U.S. testing lab’s own report for that batch, and the same batch COA is on the product page and in the COA Library.
References
- Dalmasso G, et al. PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation. Gastroenterology. 2008;134(1):166-178. PMID 18061177
- Kannengiesser K, et al. Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease. Inflamm Bowel Dis. 2008;14(3):324-331. PMID 18092346
- Brzoska T, 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. Endocr Rev. 2008;29(5):581-602. PMID 18612139
- Brzoska T, et al. Terminal signal: anti-inflammatory effects of α-melanocyte-stimulating hormone related peptides beyond the pharmacophore. Adv Exp Med Biol. 2010;681:107-116. PMID 21222263
- Xiao B, et al. Orally targeted delivery of tripeptide KPV via hyaluronic acid-functionalized nanoparticles efficiently alleviates ulcerative colitis. Mol Ther. 2017;25(7):1628-1640. PMID 28143741
Research use only. Rogue Compounds products are sold strictly for laboratory research. They are not for human or veterinary use, and nothing in this article is medical advice. The studies cited here describe published research, not this product or any use of it.