KPV

KPV is the last three amino acids of alpha-MSH, the same hormone that melanotan compounds mimic. Researchers found that this tiny fragment keeps the anti-inflammatory activity of the parent hormone but loses the pigment-darkening effect, because it no longer binds the pigment receptor. In animal models of colitis and skin inflammation it reduces inflammatory signalling. No controlled human trials have been published.

KPV is the tripeptide Lys-Pro-Val, corresponding to residues 11-13 of alpha-melanocyte stimulating hormone. Unlike the parent hormone it shows negligible melanocortin receptor binding, and its anti-inflammatory activity appears to be receptor-independent and intracellular. Reported mechanisms include direct inhibition of NF-κB nuclear translocation and DNA binding, suppression of IL-1β-induced NF-κB and MAPK signalling, and reduced production of TNF-α, IL-6 and IL-8 in stimulated cells. Intestinal uptake in colonic epithelium is reported to occur through the oligopeptide transporters PepT1 and HPT1, which are upregulated during inflammation — a mechanism that would preferentially concentrate the peptide at inflamed mucosa and is the basis for its investigation in inflammatory bowel disease models.