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immune-inflammation

KPV

Not FDA approved Lys-Pro-Val · α-MSH C-terminal tripeptide

Not FDA approved. Promising preclinical research in inflammatory bowel disease. No Phase 3 clinical trials.

What is KPV?

KPV is the C-terminal tripeptide of alpha-melanocyte-stimulating hormone (α-MSH): the amino acids Lys-Pro-Val (lysine-proline-valine) forming positions 11-13 of the molecule. This fragment retains the anti-inflammatory activity of α-MSH without activating the melanocortin receptors that produce tanning or sexual effects.

KPV research is particularly relevant for inflammatory bowel diseases (IBD) such as Crohn’s disease and Ulcerative Colitis, where preclinical models show notably promising results.

Anti-inflammatory mechanism

KPV exerts its anti-inflammatory effects through several pathways:

NF-κB inhibition:

  • NF-κB is the master transcription factor that regulates production of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-8).
  • KPV directly inhibits NF-κB activation in macrophages and intestinal epithelial cells.

Direct action on immune cells:

  • Reduces TNF-α and IL-6 production in activated macrophages.
  • Acts through intracellular receptors, not only surface receptors, allowing it to penetrate cells without requiring a specific membrane receptor.

Epithelial barrier protection:

  • In intestinal permeability models, KPV helps maintain the integrity of tight junctions in the intestinal epithelium.

Preclinical models of colitis

The strongest studies are in mice with DNBS- or DSS-induced colitis (standard IBD models):

  • Intragastric administration of KPV reduced the histological inflammation score by ~60% compared to controls.
  • Improvement in clinical parameters: weight loss, stool consistency, blood in stool.
  • No systemic toxicity observed.

An active area of research is oral delivery via nanoparticles (especially collagen or chitosan) that protect the peptide from degradation in the gastrointestinal tract and release it in the colon — where inflammation occurs in Ulcerative Colitis.

Clinical potential

Inflammatory bowel diseases affect more than 3 million people in the United States. Current treatments (mesalazine, corticosteroids, anti-TNF biologics) are effective but have limitations: cost, systemic adverse effects, loss of response.

KPV, if preclinical results replicate in humans, could represent an intestinal anti-inflammatory with an excellent safety profile and a different mechanism from current agents.

Research status

As of 2025, KPV has not entered Phase 1 clinical trials for IBD. Research is focused on optimizing oral delivery systems (nanoparticles). Injectable use in humans has no clinical evidence base.

Preclinical only for IBD. For research use only. Data are promising but exclusively from animal models. Do not use without specialized medical supervision in gastroenterology.

Reported protocol (research reference)

Vial sizes 10 mg
Reported dose Animal models of colitis: 100 mcg–1 mg/kg. No approved protocol in humans. Reported research use: 1–2 mg subcutaneous or intragastric.
Half-life Very short in plasma; rapidly degraded. Oral/intraluminal formulations are of greater interest.
FDA status Not FDA approved
Sources: J Immunology — KPV anti-inflammatory colitis ·Inflammatory Bowel Disease — KPV oral nanoparticles
This information is for educational and research reference only. It is not medical advice. We do not sell, prescribe, or recommend any treatment. Dosages cited come from research literature and are not an indication for human use. Always consult a licensed healthcare provider.