KPV
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Alpha-MSH C-terminal tripeptide (Lys-Pro-Val); potent anti-inflammatory via NF-kB inhibition and PepT1-mediated self-targeting to inflamed intestinal epithelium.
Quick Facts
| Property | Value |
|---|---|
| Also Known As | KPV, Alpha-MSH(11-13), alpha-MSH C-terminal tripeptide |
| Category | Immune / Anti-Inflammatory / Gut Health |
| Sequence | Lys-Pro-Val (3 amino acids) |
| Molecular Weight | ~344 Da |
| Molecular Formula | C16H30N4O4 |
| PubChem CID | 11083 |
| Administration | Oral / SubQ / Topical |
| Typical Dose Range | Oral 200-500 mcg BID; SubQ 200-500 mcg; Topical 0.1-1% |
| Half-Life | Short (minutes); PepT1-mediated uptake extends tissue residence |
| Storage | Lyophilized -20C 1-2 years; reconstituted 2-8C 2-4 weeks |
| FDA Status | Research-only (not approved) |
| WADA Status | Not listed |
Mechanism of Action
KPV is the C-terminal tripeptide fragment of alpha-melanocyte-stimulating hormone (alpha-MSH), retaining the parent hormone's potent anti-inflammatory activity without melanocortin receptor-mediated pigmentation or appetite effects. Its mechanism centers on direct inhibition of NF-kB nuclear translocation, which suppresses the production of pro-inflammatory cytokines including TNF-alpha, IL-6, IL-8, and IL-1beta. This NF-kB inhibition occurs both intracellularly after cellular uptake and via melanocortin receptor signaling (MC1R/MC3R agonism) at the cell surface. PMID 12750433
The most therapeutically significant property of KPV is its self-targeting in inflammatory bowel disease. The PepT1 (SLC15A1) oligopeptide transporter is dramatically upregulated on the apical surface of inflamed colonic epithelium — up to 10-fold in active Crohn's disease and ulcerative colitis. Because KPV is a tripeptide substrate for PepT1, it concentrates precisely at sites of greatest inflammation when administered orally, creating an inherent therapeutic index without requiring targeted delivery systems. PMID 18061177
KPV also stabilizes mast cells, reducing histamine release and providing anti-allergic effects relevant to atopic dermatitis and mast cell activation syndrome. Additionally, it demonstrates direct antimicrobial activity against Candida species through membrane disruption, adding an anti-infective dimension to its therapeutic profile. PMID 11268348
Key Research Areas
- Inflammatory Bowel Disease (IBD): PepT1-mediated self-targeting to inflamed colon reduces colitis severity in murine models comparable to established therapies. PMID 18092346
- NF-kB Signaling Inhibition: Direct blockade of NF-kB nuclear translocation as the core anti-inflammatory mechanism, independent of melanocortin receptor activation.
- Wound Healing: Smart-release KPV films accelerate diabetic wound closure with anti-inflammatory and re-epithelialization effects. PMID 36240893
- Atopic Dermatitis / Psoriasis: Topical application reduces skin inflammation via mast cell stabilization and cytokine suppression.
- Antimicrobial Activity: Direct membrane disruption of Candida species and selected bacteria.
- Neuroimmunomodulation: Alpha-MSH pathway modulation with implications for neuro-inflammatory conditions. PMID 11268347
Evidence Level Summary
| Evidence Type | Count | Notes |
|---|---|---|
| Human RCTs | 0 | No human RCTs to date |
| Human observational | 0 | — |
| Animal in vivo | 3 | IBD models, wound healing, host defense |
| In vitro | 2 | Keratinocyte signaling, NF-kB pathway |
| Systematic reviews | 0 | — |
| Narrative reviews | 3 | Alpha-MSH peptide class reviews |
Clinical Applications
- Gut Health — PepT1-mediated oral delivery to inflamed colon; IBD, Crohn's, UC
- Immune Support — NF-kB inhibition, broad anti-inflammatory
- Wound Healing — Smart-release films, diabetic wound acceleration
- Skin Health — Atopic dermatitis, psoriasis, eczema
- Autoimmune Conditions — Mast cell stabilization, cytokine suppression
Protocols Using This Peptide
Ageless Peps Products
- AP-KPV-Vial — KPV 5mg Vial, $50
- AP-KPV-Capsules — KPV 500mcg Capsules (60ct), $133
- AP-BPC157-KPV-Capsules — BPC-157/KPV Blend Capsules, $284
Dosing Reference
Research Dosing Ranges (from literature)
| Route | Dose Range | Frequency | Duration | Source |
|---|---|---|---|---|
| Oral | 200-500 mcg | BID, empty stomach | 4-8 weeks | Practitioner guides |
| SubQ | 200-500 mcg | 1-2x daily | 4-6 weeks | Practitioner guides |
| Topical | 0.1-1% | 1-2x daily | As needed | PMID 36240893 |
Cycling
Typical protocols: 4-8 weeks on, 2-4 weeks off. Oral route preferred for GI conditions due to PepT1-mediated self-targeting. Effects may be cumulative. No dependency or tolerance reported.
Contraindications & Safety
- Contraindications: No absolute contraindications established; caution in pregnancy/nursing (insufficient data)
- Common side effects: Minimal; well tolerated orally and topically given endogenous origin (alpha-MSH fragment)
- Drug interactions: No known clinically significant interactions; theoretical additive effect with other anti-inflammatory agents
- Pregnancy/nursing: Insufficient data; avoid
- Special populations: No specific adjustments known for renal/hepatic impairment
Synergistic Combinations
- BPC-157 + KPV — Gut healing synergy; BPC-157 angiogenic + KPV anti-inflammatory (available as AP-BPC157-KPV-Capsules)
- LL-37 + KPV — Antimicrobial + anti-inflammatory combination for infections with inflammatory component
- TB-500 + KPV — Anti-inflammatory + tissue repair synergy (available in AP-KLOW-Blend)
Related Research
| PMID | Title | Year | Study Type |
|---|---|---|---|
| 15102092 | alpha-MSH, MSH 11-13 KPV and adrenocorticotropic hormone signalling in human keratinocyte cells | 2004 | In vitro |
| 12750433 | Dissection of the anti-inflammatory effect of the core and C-terminal alpha-MSH peptides | 2003 | In vitro |
| 17934097 | alpha-MSH related peptides: a new class of anti-inflammatory and immunomodulating drugs | 2007 | Review |
| 11268348 | The neuropeptide alpha-MSH in host defense | 2001 | Review |
| 11268347 | The neuroimmunomodulatory peptide alpha-MSH | 2001 | Review |
| 18061177 | KPV PepT1-Mediated Uptake Reduces Intestinal Inflammation | 2008 | Animal in vivo |
| 18092346 | KPV Anti-Inflammatory Potential in Murine IBD | 2008 | Animal in vivo |
| 36240893 | KPV Smart-Release Film for Diabetic Wound Healing | 2022 | Animal in vivo |
References
- PMID 15102092 — Keratinocyte signaling
- PMID 12750433 — Anti-inflammatory dissection
- PMID 17934097 — Alpha-MSH class review
- PMID 11268348 — Host defense
- PMID 11268347 — Neuroimmunomodulation
- PMID 18061177 — PepT1 uptake IBD
- PMID 18092346 — Murine IBD
- PMID 36240893 — Diabetic wound healing
Related
#peptide #immune #gastrointestinal #subq #oral