Scientific Reference
KPV (Lys-Pro-Val)
Evidence profile: Predominantly preclinical
KPV is the tripeptide lysine–proline–valine, corresponding to the last three residues of alpha-melanocyte-stimulating hormone (α-MSH). It lacks the His-Phe-Arg-Trp core sequence through which α-MSH activates melanocortin receptors, so its pharmacology cannot be assumed to match that of the parent hormone. Interest in it follows reports that C-terminal fragments of α-MSH alter inflammatory signalling in cell and animal models. Published studies are mainly in cultured epithelial and immune cells and in mouse models of chemically induced colitis. The literature is small, and human data are scarce.
Mechanism of Action
How KPV acts has not been settled. Cell studies have reported that it lowers activation of the transcription factor NF-κB and reduces expression of inflammatory cytokines in intestinal epithelial and immune cell lines. In intestinal epithelial cells, uptake through the di- and tripeptide transporter PepT1 has been reported, which would allow it to act inside the cell rather than at a surface receptor. Whether it also signals through melanocortin receptors such as MC1R is disputed, since reports differ and its sequence lacks the usual receptor-binding motif. The mechanistic work is limited and comes largely from cell and rodent models.
Molecular Information
- Type: Tripeptide (alpha-MSH fragment)