KPV

KPV is the tripeptide Lys-Pro-Val. It is the C-terminal fragment of α-MSH, at residues 11 to 13.

It is an anti-inflammatory melanocortin fragment. It has no pigmentary activity. This separates it from Melanotan I and Melanotan II.

The action is largely intracellular and does not depend on a receptor.

KPV inhibits NF-κB. It blocks the degradation of IκBα and the nuclear import of p65. It also inhibits MAPK signaling.

The result is a decrease in TNF-α, IL-1β, and IL-6.

It enters intestinal cells and immune cells through the PepT1 transporter. Inflamed gut tissue increases PepT1.

Evidence tier: preclinical only.

Hiltz and Lipton (1989) established the anti-inflammatory activity.

KPV works across murine DSS and TNBS colitis models.

Xiao et al. (Gastroenterology, 2017) delivered KPV in hyaluronic-acid-functionalized nanoparticles. That formulation worked at a dose about 12,000-fold lower in a mouse model of ulcerative colitis.

PepT1-knockout studies confirm that the effect depends on the transporter.

Evidence limit. No human randomized controlled trial finished.

No high-authority human dosing exists.

Cellular uptake depends on PepT1. No source characterizes human pharmacokinetics.

No documented interaction exists.

Compare with Thymosin Alpha-1 and BPC-157.

Preclinical models showed no significant toxicity. Human safety data are essentially absent.

No validated biomarker exists.

No regulator approves KPV.

At the July 2026 PCAC meeting the FDA proposed not to add KPV to the 503A bulks list. Read the PCAC July 2026 outcome.

WADA does not name it.