KPV
Also known as: Lys-Pro-Val, alpha-MSH(11-13), alpha-MSH C-terminal tripeptide
Grey-Market Compound. This compound is not approved by the FDA or any major regulatory authority. No established regimen exists. Products available outside of regulated channels lack standardized manufacturing, quality control, and potency verification. Consult a qualified clinician. Research-only risks apply.
Overview
Clinical Summary
KPV is a tripeptide (Lys-Pro-Val) derived from the C-terminal end of alpha-melanocyte-stimulating hormone (alpha-MSH). It retains the anti-inflammatory properties of the parent hormone without significant melanocortin receptor binding or pigmentation effects. Preclinical studies have demonstrated potent anti-inflammatory activity through direct inhibition of NF-kappaB nuclear translocation in epithelial and immune cells. Interest in KPV centers on gastrointestinal inflammation and dermatologic conditions, but no human clinical trials have been conducted. It is available through grey-market peptide suppliers and compounding pharmacies in some jurisdictions.
Plain Language Summary
KPV is a small fragment of a natural hormone called alpha-MSH that helps control inflammation in the body. Researchers are interested in it because animal studies suggest it can reduce gut inflammation and may help with skin conditions. It has not been tested in human clinical trials, so its safety and effectiveness in people are not established. It is currently available only through unregulated sources.
Mechanism of Action
KPV exerts anti-inflammatory effects primarily through inhibition of NF-kappaB, a master transcription factor that drives inflammatory gene expression. Unlike full-length alpha-MSH, KPV does not require melanocortin receptors (MC1R through MC5R) for its anti-inflammatory activity and appears to act through direct intracellular mechanisms after cellular uptake. KPV enters cells via peptide transport systems and inhibits IKK-beta phosphorylation, preventing NF-kappaB nuclear translocation. This results in reduced production of pro-inflammatory cytokines including TNF-alpha, IL-1beta, and IL-8. In colonic epithelial models, KPV also reduced chemokine-mediated neutrophil recruitment.
Evidence Summary
Evidence for KPV is limited to preclinical studies. Dalmasso et al. (2008) demonstrated that KPV loaded into nanoparticles reduced colonic inflammation in a murine DSS colitis model, with reduced MPO activity and histological damage scores. Kannengiesser et al. (2008) showed KPV reduced IL-8 and TNF-alpha production in human intestinal epithelial cell lines. No randomized controlled trials, pharmacokinetic studies, or dose-finding studies in humans have been published. The translation from preclinical promise to clinical application remains unvalidated.
Safety Profile
No formal human safety data exist for KPV. In preclinical models, no significant toxicity has been reported. As a naturally occurring tripeptide fragment, it is presumed to have low inherent toxicity, but this has not been confirmed through standard toxicology studies. Grey-market products carry risks related to purity, sterility, and accurate dosing. The lack of human pharmacokinetic data means optimal dosing, bioavailability, and duration of effect are unknown.
Contraindications
- Known hypersensitivity to KPV or related melanocortin peptides
- Pregnancy and breastfeeding (no safety data)
- Active malignancy (theoretical concern with immunomodulation)
Adverse Events
- No systematic adverse event data from human studies
- Injection site reactions (reported anecdotally)
- Theoretical risk of immunosuppression with chronic use
Interactions
- No formal drug interaction studies conducted
- Theoretical interaction with immunosuppressive therapies (additive immunomodulation)
- May interact with other NF-kappaB pathway modulators
Regulatory Notes
KPV has no regulatory approval in any jurisdiction. It is not FDA-approved and has not entered formal clinical development. It is available through grey-market peptide suppliers and some compounding pharmacies. Products are not manufactured under validated GMP conditions and lack standardized quality controls. The FDA has not specifically addressed KPV in compounding guidance as of the last review date.
Monitoring Considerations
No evidence-based monitoring guidelines exist. Clinicians using KPV off-label may consider monitoring inflammatory markers (CRP, ESR, fecal calprotectin for GI applications), complete blood count for immunomodulatory effects, and hepatic and renal function panels at baseline and periodically. Skin assessment if used for dermatologic conditions.
These are general considerations for clinical awareness and do not constitute prescriptive monitoring recommendations for any individual patient.
Stability and Handling Notes
KPV is typically supplied as a lyophilized powder. Reconstitution is generally performed with bacteriostatic water. As a small tripeptide, it may be susceptible to degradation in solution. Reconstituted product should be refrigerated (2 to 8 degrees C) and used within a timeframe consistent with peptide stability, though formal stability data are not publicly available. Protect from light and avoid repeated freeze-thaw cycles.
References
- 1preclinical
KPV (alpha-MSH C-terminal Tripeptide) Inhibits NF-kappaB and Protects Against Experimental Colitis
Dalmasso G, Charrier-Hisamuddin L, Nguyen HT, et al. (2008). Journal of Biological Chemistry
Key findings: KPV inhibited NF-kappaB activation in colonic epithelial cells and reduced inflammation in a murine colitis model when administered orally in nanoparticles.
Limitations: Mouse model only. Oral nanoparticle delivery system not yet validated in humans.
View source - 2preclinical
Alpha-MSH and Its Tripeptide Analogue KPV Exert Anti-inflammatory Effects on Intestinal Epithelial Cells
Kannengiesser K, Maaser C, Heidemann J, et al. (2008). Inflammatory Bowel Diseases
Key findings: KPV reduced proinflammatory cytokine production (IL-8, TNF-alpha) in human intestinal epithelial cell lines exposed to inflammatory stimuli.
Limitations: In vitro study. Cell line behavior may not reflect intact tissue responses.
- 3review
Anti-inflammatory Properties of the Melanocortin Peptides and Their Fragments
Brzoska T, Luger TA, Maaser C, et al. (2008). Annals of the New York Academy of Sciences
Key findings: Comprehensive review of alpha-MSH and its C-terminal tripeptide KPV, detailing anti-inflammatory signaling through NF-kappaB inhibition, cytokine modulation, and potential therapeutic applications in inflammatory diseases.
Limitations: Review of predominantly preclinical literature. No human clinical trial data available.
Last reviewed: 2024-12-20 | Version: 1 | Status: Published
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