KPV — Anti-inflammatory tripeptide — C-terminal fragment of alpha-MSH / melanocortin receptor ligand

KPV is the C-terminal tripeptide (Lys-Pro-Val) of alpha-MSH (alpha-melanocyte-stimulating hormone). Alpha-MSH's full-length anti-inflammatory activity is concentrated in its C-terminal KPV sequence, allowing oral or topical delivery without melanotropic (tanning) effects of the full peptide. Mechanisms: (1) MC1R and MC3R agonism — activates melanocortin receptors expressed on macrophages, monocytes, and dendritic cells, suppressing NF-κB signaling and reducing TNF-α, IL-1β, IL-6, and IL-8; (2) Intestinal epithelial NF-κB inhibition — maintains tight junction integrity and reduces intestinal permeability; (3) Crosses intestinal epithelium intact via oral route (intact tripeptide absorption confirmed in animal studies); (4) Activates anti-apoptotic pathways in enterocytes. CRITICAL LIMITATION: all human-relevant mechanistic data is from rodent colitis models (DSS-colitis, TNBS-colitis). No published human clinical trials as of 2024.

Overview

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Compound Class

Anti-inflammatory tripeptide — C-terminal fragment of alpha-MSH / melanocortin receptor ligand

Mechanism of Action

KPV is the C-terminal tripeptide (Lys-Pro-Val) of alpha-MSH (alpha-melanocyte-stimulating hormone). Alpha-MSH's full-length anti-inflammatory activity is concentrated in its C-terminal KPV sequence, allowing oral or topical delivery without melanotropic (tanning) effects of the full peptide. Mechanisms: (1) MC1R and MC3R agonism — activates melanocortin receptors expressed on macrophages, monocytes, and dendritic cells, suppressing NF-κB signaling and reducing TNF-α, IL-1β, IL-6, and IL-8; (2) Intestinal epithelial NF-κB inhibition — maintains tight junction integrity and reduces intestinal permeability; (3) Crosses intestinal epithelium intact via oral route (intact tripeptide absorption confirmed in animal studies); (4) Activates anti-apoptotic pathways in enterocytes. CRITICAL LIMITATION: all human-relevant mechanistic data is from rodent colitis models (DSS-colitis, TNBS-colitis). No published human clinical trials as of 2024.

Regulatory Status

NOT FDA approved. No IND application on file. Research chemical only. Do not use in clinical practice without IRB-approved protocol.

Evidence Level

D — PRECLINICAL ONLY. All evidence from DSS-colitis and TNBS-colitis mouse/rat models. No published Phase 1 human safety trial as of 2024. Cannot be applied clinically without human data.