KPV
Melanocortin-Derived Tripeptide & NF-κB Suppression
KPV — α-MSH(11–13) Anti-Inflammatory Tripeptide (Lys-Pro-Val)
Last reviewed: September 2026
KPV is the last three amino acids of α-MSH, a hormone best known for tanning. Those three amino acids keep the hormone's anti-inflammatory power but not its pigment effect. In mice, KPV taken by mouth reduced colitis; the peptide is small enough to be carried into gut cells by the gut's own peptide transporter.
Inside cells, KPV switches off NF-κB, the master inflammatory transcription factor, reducing inflammatory cytokines such as TNF-α and IL-6. It has been studied mainly in inflammatory bowel disease models and in skin cells.
A small, orally active anti-inflammatory peptide with a defined uptake route is an attractive research tool for gut inflammation. An FDA advisory panel's 2026 vote to recommend KPV for compounding has raised its profile.
All efficacy evidence is in mice and cells. There are no controlled human trials. The FDA panel vote is a regulatory step about compounding eligibility, not proof it works in people. Research-only.
What is KPV?
KPV is the C-terminal tripeptide of α-melanocyte-stimulating hormone (α-MSH residues 11–13). It retains the anti-inflammatory activity of the parent hormone while lacking the pigmentary (MC1R-driven melanogenic) effects, which is why it was isolated as a research tool in the 1990s. The best-characterised work is in intestinal inflammation: KPV is transported into intestinal epithelial and immune cells by the oligopeptide transporter PepT1, where it suppresses NF-κB activation and pro-inflammatory cytokine output, and oral KPV reduced colitis severity in DSS and TNBS mouse models.
Interest in KPV rose in 2026 when an FDA advisory panel voted to recommend it for the 503A bulk-substances list for compounding — a regulatory signal, not a proof of efficacy. All efficacy data remain preclinical; there are no controlled human trials of KPV as a therapeutic.
- KPV (Lys-Pro-Val, 342.4 Da) is the C-terminal tripeptide of α-MSH; it keeps the anti-inflammatory activity and drops the pigmentary effect.
- Mechanism: PepT1 transporter uptake into intestinal epithelial and immune cells → NF-κB inhibition → reduced TNF-α, IL-6, IL-8, IL-1β.
- Oral KPV reduced DSS and TNBS colitis in mice (Dalmasso 2008; Kannengiesser 2008); nanoparticle delivery cut the effective dose ~12,000-fold (Xiao 2017).
- No controlled human trials exist. The July 2026 FDA advisory-panel vote (8–6) concerned 503A compounding eligibility, not efficacy or approval.
- Purgo Labs sells KPV as a 10mg vial ($39.99, read 10 Sep 2026) and includes 10mg of KPV in its KLOW blend.
Molecular Composition
KPV is a linear tripeptide, Lys-Pro-Val (342.4 Da, C16H30N4O4), identical to residues 11–13 of α-MSH. The sequence is small enough to be a substrate of PepT1 (SLC15A1), the di/tripeptide transporter expressed on intestinal epithelium and, under inflammatory conditions, on immune cells — the property that gives KPV oral bioavailability into the gut wall that larger peptides lack. Supplied as a lyophilized powder for reconstitution.
How Does It Work?
KPV is taken up by the PepT1 transporter into gut and immune cells, where it blocks NF-κB and cuts TNF-α, IL-6 and IL-1β output — reducing inflammation in mouse colitis models without α-MSH's pigment effects.
KPV exerts anti-inflammatory effects through at least two routes. First, unlike full-length α-MSH it does not require melanocortin receptor signalling for much of its effect: after PepT1-mediated uptake into epithelial and immune cells, KPV inhibits NF-κB nuclear translocation and downstream transcription of TNF-α, IL-6, IL-8 and IL-1β. Second, KPV can interact directly with the IL-1β signalling axis, which was the basis of the original antipyretic and anti-inflammatory patents.
In colitis models, oral KPV reduced weight loss, colonic shortening, histological damage and MPO activity, and lowered pro-inflammatory cytokine expression; the effect was lost in PepT1-deficient conditions, tying the mechanism to transporter-mediated uptake. KPV also reduced inflammatory signalling in keratinocytes and models of dermal inflammation, consistent with the broad anti-inflammatory profile of the melanocortin C-terminus.
Key Research Pathways
PepT1-Mediated Cellular Uptake
KPV is a substrate of the intestinal di/tripeptide transporter PepT1, giving it access to epithelial and infiltrating immune cells — and oral activity in gut models.
NF-κB Inhibition
Intracellular KPV blocks NF-κB nuclear translocation, reducing transcription of TNF-α, IL-6, IL-8 and IL-1β.
IL-1β Axis Antagonism
KPV's original antipyretic activity was attributed to interference with IL-1β signalling, independent of melanocortin receptors.
Melanocortin-Receptor-Independent Action
Much of KPV's effect persists without MC1R engagement, which separates its anti-inflammatory activity from α-MSH's pigmentary effects.
Key Findings from the Literature
- Oral KPV reduced DSS- and TNBS-induced colitis in mice, with lower pro-inflammatory cytokine expression; uptake occurred via PepT1 on intestinal epithelial and immune cells (Dalmasso et al., Gastroenterology 2008; PMID 18061177)
- KPV ameliorated disease in murine IBD models and inhibited NF-κB activation in intestinal epithelial cells and T cells (Kannengiesser et al., Inflamm Bowel Dis 2008; PMID 18092346)
- KPV retains α-MSH's anti-inflammatory and antipyretic activity without melanogenic (pigmentary) effects — the reason the tripeptide was isolated (Brzoska et al., Endocrine Reviews 2008)
- Hyaluronic-acid-functionalised nanoparticles loaded with KPV alleviated ulcerative colitis in mice at ~12,000-fold lower dose than free KPV in drinking water (Xiao et al., Molecular Therapy 2017)
- On 23–24 July 2026 an FDA advisory panel voted 8–6 to recommend KPV for the 503A bulk-substances list for compounding — a regulatory step, not a demonstration of clinical efficacy
Important Research Context
Research References
Peer-reviewed literature supporting the research profile of KPV
The following peer-reviewed studies form the primary evidence base for KPV's research profile. All references are sourced from PubMed, NCBI, and peer-reviewed scientific journals. Published research is available through PubMed, NCBI, and peer-reviewed biomedical journals.
- 1.
Dalmasso G, et al. PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation. Gastroenterology. 2008.PMID: 18061177
KPV entered intestinal epithelial and immune cells via PepT1 and oral KPV reduced DSS and TNBS colitis with lower pro-inflammatory cytokine expression.
- 2.
Kannengiesser K, et al. Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease. Inflammatory Bowel Diseases. 2008.PMID: 18092346
KPV ameliorated murine colitis and inhibited NF-κB activation in epithelial cells and T cells.
- 3.
Brzoska T, et al. α-Melanocyte-stimulating hormone and related tripeptides: biochemistry, antiinflammatory and protective effects in vitro and in vivo, and future perspectives for the treatment of immune-mediated inflammatory diseases. Endocrine Reviews. 2008.PMID: 18612139
Review establishing KPV as the minimal anti-inflammatory motif of α-MSH, active without melanogenic effects.
- 4.
Xiao B, et al. Orally targeted delivery of tripeptide KPV via hyaluronic acid-functionalized nanoparticles efficiently alleviates ulcerative colitis. Molecular Therapy. 2017.PMID: 28143741
HA-functionalised KPV nanoparticles alleviated UC in mice at ~12,000-fold lower dose than free KPV.
KPV
Immune Research
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Technical Specifications
| Peptide Class | Melanocortin C-terminal tripeptide (α-MSH 11–13) |
| Sequence | Lys-Pro-Val |
| Molecular Weight | 342.4 Da |
| Primary Uptake Route | PepT1 (SLC15A1) di/tripeptide transporter |
| Key Pathway | NF-κB inhibition; TNF-α / IL-6 / IL-1β suppression |
| Available Size | 10mg vial (3 mL) |
| Form | Lyophilized powder |
| Purity | ≥99% (third-party COA) |
Source KPV at Purgo Labs
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Other Compounds in This Guide
Supporting Research
KPV has consistent preclinical evidence for reducing intestinal inflammation via PepT1 uptake and NF-κB inhibition, and in-vitro anti-inflammatory activity in skin and immune cells. No controlled human trials exist.
References
Research Databases
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