Educational reference, not medical advice. This page summarizes information from published research and regulatory filings for educational purposes. It is not a recommendation to use any compound and should not replace guidance from a licensed healthcare provider. Most peptides discussed here are not approved for the uses described.
What it is
KPV is the C-terminal tripeptide (lysine-proline-valine, residues 11-13) of α-melanocyte-stimulating hormone (α-MSH). It carries much of the anti-inflammatory activity of the full α-MSH hormone but lacks the melanocortin receptor 1 binding affinity that would cause skin pigmentation. It is sometimes referred to as α-MSH(11-13).
History
The anti-inflammatory effects of α-MSH were characterized through the 1990s in models of sepsis, brain inflammation, and inflammatory bowel disease. Investigators in Milan and New Mexico subsequently dissected the molecule and identified KPV as the minimal active fragment retaining anti-inflammatory potency. Most published work since 2000 has focused on KPV in inflammatory bowel disease, including a Gastroenterology paper in 2008 demonstrating reduced colitis severity in mice given oral KPV — an effect attributed to active uptake by the intestinal PepT1 transporter.
Regulatory status
KPV has not been approved for any therapeutic use in any country. The most advanced clinical development has been in inflammatory bowel disease as an oral formulation, but no registered Phase III trial exists. It is available through research peptide suppliers and through some compounding pharmacies that prepare it for oral or topical use; injectable preparations are less common and more legally constrained.
Mechanism
The published mechanism papers describe several distinct anti-inflammatory and antimicrobial effects:
- NF-κB suppression in macrophages and intestinal epithelial cells, reducing transcription of TNF-α, IL-6, and IL-8.
- MC1R-independent effects — KPV does not bind melanocortin receptors with appreciable affinity, but it appears to act through direct cytosolic targets after PepT1-mediated uptake.
- Antimicrobial activity against gram-positive and gram-negative bacteria and fungi, demonstrated in 2000 by the Cutuli group with potencies in the micromolar range.
- Mast cell stabilization, suggesting a possible role in atopic skin and gut conditions.
Half-life and dosing intervals
KPV is a very small tripeptide and is rapidly cleared from circulation — published estimates put the half-life at roughly 20–30 minutes after subcutaneous injection. Its oral activity is dependent on the PepT1 transporter, which is present at high density in the small intestine.
Oral KPV doses described in animal colitis studies range from 1 to 10 µg/kg per day. Observational protocols in research peptide channels typically describe 500 µg to 1 mg per day, oral or subcutaneous, often for short cycles. None of these regimens are derived from controlled human dose-finding studies.
Reconstitution example
KPV is typically supplied in 5 mg or 10 mg lyophilized vials. A 5 mg vial reconstituted with 2 mL of bacteriostatic water yields 2.5 mg/mL. On a 1 mL U-100 insulin syringe, 4 units (0.04 mL) delivers 100 mcg. Oral formulations require enteric protection to survive gastric pH; capsule formats are produced by compounding pharmacies for this purpose.
What to know
- Limited human data. No registered late-phase human trial exists. Most evidence comes from rodent colitis models and in vitro mechanism work.
- Antimicrobial activity is documented in vitro but should not be interpreted as a treatment for any infection.
- Storage. Refrigerate lyophilized vials. Reconstituted KPV is refrigerator-stable for up to 4 weeks per common stability data.
- Reported side effects in available data are minimal at studied doses; the compound is generally well-tolerated in animal models.
Sources
- 1.Catania A et al. (2004). Targeting melanocortin receptors as a novel strategy to control inflammation. Pharmacological Reviews.
- 2.Bettenworth D et al. (2011). Anti-inflammatory effect of the α-MSH tripeptide KPV in experimental colitis. Inflammatory Bowel Diseases.
- 3.Cutuli M et al. (2000). Antimicrobial effects of α-MSH peptides. Journal of Leukocyte Biology.
- 4.Dalmasso G et al. (2008). PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation. Gastroenterology.