KPV (Lys-Pro-Val) — alpha-MSH C-Terminal Tripeptide
Also Known AsLys-Pro-Val · alpha-MSH(11-13) · KPV tripeptide · C-terminal alpha-MSH fragment
C-terminal tripeptide fragment (residues 11-13) of alpha-melanocyte-stimulating hormone (alpha-MSH). Research by James Lipton and Anna Catania demonstrated that the anti-inflammatory activity of alpha-MSH resides primarily in this C-terminal KPV sequence, which retains potent anti-inflammatory effects without melanocortin receptor binding or melanogenic activity.
Lys-Pro-ValHow KPV Works
NF-kB Signaling Inhibition
KPV inhibits NF-kB activation by preventing IkB-alpha phosphorylation and degradation, thereby blocking nuclear translocation of NF-kB p50/p65 dimers. This reduces transcription of pro-inflammatory cytokines (TNF-alpha, IL-1beta, IL-6, IL-8), chemokines, adhesion molecules, and inducible enzymes (iNOS, COX-2). The mechanism is independent of melanocortin receptors.
MAPK Pathway Modulation
KPV modulates mitogen-activated protein kinase (MAPK) signaling, reducing phosphorylation of JNK and p38 MAPK in inflammatory cell models. This attenuates AP-1 transcription factor activation and downstream inflammatory gene expression, representing a second anti-inflammatory axis independent of NF-kB.
Direct Intracellular Entry
KPV enters cells via the peptide transporter PepT1 (SLC15A1), which is expressed on intestinal epithelial cells and immune cells. Once intracellular, KPV directly modulates inflammatory signaling cascades. This PepT1-mediated uptake is particularly relevant for GI applications where PepT1 expression is high on the apical surface of enterocytes.
Published Research
Inflammatory Bowel Disease Models
ModerateKPV demonstrates efficacy in DSS-induced colitis, TNBS colitis, and Citrobacter rodentium infection models. Oral and rectal administration reduce colonic inflammation scores, neutrophil infiltration (MPO activity), and pro-inflammatory cytokine levels. PepT1-mediated uptake by colonocytes provides a mechanistic basis for oral/rectal efficacy in GI inflammation.
Cutaneous Inflammation
ModerateKPV reduces inflammatory responses in skin models including contact hypersensitivity, UV-induced inflammation, and irritant dermatitis. Effects include reduced edema, leukocyte infiltration, and pro-inflammatory cytokine production. The anti-inflammatory mechanism (NF-kB/MAPK inhibition) applies across tissue types.
Immune Cell Modulation
ModerateIn vitro studies with macrophages, dendritic cells, and T-lymphocytes demonstrate that KPV reduces LPS-stimulated TNF-alpha and IL-6 secretion, inhibits dendritic cell maturation, and promotes an anti-inflammatory macrophage phenotype. Effects are melanocortin receptor-independent.
Wound Healing
PreclinicalThe anti-inflammatory and tissue-protective properties of KPV support wound healing in inflammatory environments. Studies show reduced wound inflammation and improved re-epithelialization in models where excessive inflammation delays healing.
Safety Profile
KPV is a naturally occurring endogenous tripeptide fragment of alpha-MSH. Preclinical studies demonstrate no toxicity at effective doses. Unlike full-length alpha-MSH or synthetic melanocortin agonists (e.g., melanotan), KPV does not bind melanocortin receptors and therefore does not produce melanogenic, cardiovascular, or sexual arousal effects. No human clinical trials have been conducted, but the endogenous origin and minimal peptide size contribute to a favorable theoretical safety profile.
Handling & Storage
KPV is a small, stable tripeptide with good aqueous solubility. Reconstitute with bacteriostatic water. Store lyophilized powder at -20°C. Reconstituted solution at 2-8°C, use within 28 days. The small size (342 Da) confers stability advantages over larger peptides.
Peer-Reviewed Literature
- 1
Alpha-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
Brzoska T, Luger TA, Maaser C, et al.
- 2
PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation
Dalmasso G, Charrier-Hisamuddin L, Nguyen HTT, et al.
- 3
Targeting melanocortin receptors as a novel strategy to control inflammation
Catania A, Gatti S, Colombo G, Lipton JM.
- 4
alpha-MSH related peptides: a new class of anti-inflammatory and immunomodulating drugs
Luger TA, Brzoska T.
KPV FAQ
What is KPV?
KPV (Lys-Pro-Val) is the C-terminal tripeptide fragment (residues 11-13) of alpha-melanocyte-stimulating hormone (alpha-MSH). It retains the anti-inflammatory activity of the parent hormone — inhibiting NF-kB and MAPK signaling — without binding melanocortin receptors or producing melanogenic effects.
How does KPV differ from alpha-MSH?
Alpha-MSH is a 13-amino-acid peptide that activates melanocortin receptors (MC1R-MC5R), producing anti-inflammatory, melanogenic, and neuroendocrine effects. KPV contains only the last 3 amino acids and works through a melanocortin receptor-independent mechanism (direct intracellular NF-kB inhibition via PepT1 uptake). This means anti-inflammatory activity without skin darkening or other melanocortin effects.
Can KPV be taken orally?
KPV is a research compound. Preclinically, oral administration showed efficacy in colitis models, with PepT1-mediated uptake in intestinal epithelium providing a mechanistic basis for GI bioavailability. The small tripeptide size (342 Da) may confer better GI stability than larger peptides, though systematic oral bioavailability data is limited.
Does KPV cause skin darkening?
No. Unlike alpha-MSH, melanotan I, or melanotan II, KPV does not bind melanocortin receptors (particularly MC1R) and therefore does not stimulate melanogenesis. Its anti-inflammatory effects operate through a melanocortin receptor-independent intracellular mechanism.
How should KPV be stored?
Store lyophilized KPV at -20°C. Reconstitute with bacteriostatic water. The small tripeptide is relatively stable — refrigerate reconstituted solution at 2-8°C and use within 28 days.
KPV Products
All compounds 99%+ purity, verified by Janoshik Analytical. GMP-manufactured lyophilized powder.
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Disclaimer: This monograph is provided for educational and research purposes only. G26x Peptides products are sold exclusively as research chemicals. They are not intended for human consumption, therapeutic use, or as dietary supplements. All research should be conducted in compliance with applicable laws and institutional review board protocols. Information presented here is sourced from published peer-reviewed literature and does not constitute medical advice.