KPV (Lys-Pro-Val)
α-MSH–derived tripeptide studied for NF-κB suppression at barrier tissues (gut, skin, cornea). Non-pigmenting melanocortin fragment with PepT1-mediated epithelial uptake.
⚡ Executive Summary
KPV (Lys-Pro-Val) is the C-terminal tripeptide of α-MSH studied for its ability to reduce NF-κB–mediated inflammation at epithelial barriers. Mechanistically, it acts independently of classical melanocortin receptors and is transported by PepT1 in gut epithelium. Animal and cell studies show reduced cytokine signaling (TNF-α, IL-6, IL-8) and tissue injury. ✓ Non-Pigmenting
Jump to section
Overview
🔥 What is KPV?
KPV (Lys-Pro-Val) is the C-terminal tripeptide of α-melanocyte-stimulating hormone (α-MSH), also known as α-MSH(11-13).
It preserves α-MSH’s anti-inflammatory signal without the melanogenic (pigmenting) effect — a major reason it’s studied as a targeted anti-inflammatory tripeptide.
🎯 Target Tissues
-
🫁
Gut epithelium — colitis models, PepT1 transport
-
🧴
Skin/keratinocytes — non-pigmenting
-
👁️
Ocular surface — corneal wound healing
Key insight: Think of KPV as a “precision tripeptide” that rides epithelial transport (PepT1) to quieten the local transcriptional noise (NF-κB) that keeps barrier tissues inflamed — without the pigment changes that complicate α-MSH.
Research only: Human randomized trials are limited. Most data are from cell and animal models. Does not establish clinical efficacy or safety for therapeutic use.
Entity Properties
| Aliases | KPV, α-MSH(11-13), ACTH(11-13) |
|---|---|
| Sequence | H-Lys-Pro-Val-OH (K-P-V) |
| Length | 3 amino acids (tripeptide) |
| Molecular Weight | ~342.43 Da (free acid) |
| CAS Number | 67727-97-3 |
| Family | Melanocortin-derived tripeptide; NF-κB pathway modulator |
| Transport | PepT1 (SLC15A1) in gut epithelium |
| Diluent(s) | Sterile water, 0.9% saline, or bacteriostatic water |
| Research Conc. | 10 nM (cells), 1-10 μM (cornea), 100 μM (oral mice) |
| Storage (dry) | −20°C, dry, dark; stable long-term |
| Storage (solution) | 2–8°C short-term, −20°C longer-term; avoid freeze-thaw |
Mechanism of Action
🧠 How does KPV work?
KPV reduces NF-κB signaling in epithelial and immune cells. In gut models, this depends on PepT1 uptake rather than classical melanocortin receptor signaling.
In Caco-2/HT29 intestinal cells, KPV (10 nM) decreased NF-κB–luciferase activity and IκB-α degradation. In mice, KPV in drinking water (100 μM) reduced DSS/TNBS colitis severity and cytokine expression.
🔒 NF-κB Suppression
Reduces NF-κB activation and downstream cytokines (TNF-α, IL-6, IL-8) at barrier tissues
🚪 PepT1 Transport
Epithelial uptake via PepT1 di/tripeptide transporter in gut — distinct from receptor agonism
✓ MCR-Independent
Anti-inflammatory effect doesn’t require melanocortin receptor-cAMP signaling in epithelium
Independence from melanocortin receptors: While α-MSH activates cAMP via MC1R/MC3R/MC5R, KPV’s anti-inflammatory effect in epithelium did NOT mirror α-MSH’s cAMP profile — supporting a receptor-independent or transporter-facilitated mechanism.
Why this matters: Because NF-κB orchestrates many inflammatory genes at barrier tissues, small decreases in NF-κB activation yield measurable improvements in tissue integrity, wound closure, and cytokine profiles.
Research Evidence
🔬 Evidence by System
Gut & Intestinal Barrier
Oral KPV (100 μM) reduced colitis severity in DSS/TNBS models with lower cytokines and histologic inflammation. PepT1 expression required for effect.
Skin & Keratinocytes
KPV inhibits TNF-α–stimulated NF-κB in keratinocytes while avoiding pigmentation — central for dermatology research.
Ocular Surface
Topical KPV (1-10 μM) accelerated corneal epithelial wound closure in rabbits. NO signaling contributory (diminished by L-NAME).
CNS Injury (Exploratory)
Single α-MSH(11-13) administration decreased tissue damage after controlled cortical impact in mice (TBI model).
Unifying outcome: Across all systems, the result is less NF-κB–driven inflammation at barrier tissues with minimal pigmentary change — valuable for research on epithelial integrity, wound repair, and cytokine normalization.
Delivery Considerations
KPV’s delivery route should match the target tissue. The peptide’s hydrophilicity affects skin permeation but enables PepT1-mediated gut uptake.
Oral (Gut)
100 μM in drinking water reduced colitis in mice. PepT1 enables enterocyte uptake in small intestine (inducible in inflamed colon).
Topical (Skin)
Microneedles + iontophoresis significantly increased KPV permeation across human skin — device-assisted delivery viable.
Ocular (Drops)
1-10 μM topical improved corneal re-epithelialization. Multiple daily instillations may enhance outcomes.
Lab handling: Short peptides are commonly reconstituted in sterile aqueous solutions (SWFI, PBS, or bac water) and aliquoted to minimize freeze-thaw cycles. Follow institutional SOPs and CoA guidance.
Define Tissue & Endpoint
Specify barrier tissue (gut, skin, cornea) and primary readout (NF-κB, cytokines, wound closure).
Match Delivery Route
Oral for gut; microneedles ± iontophoresis for skin; topical drops for cornea.
Anchor Concentrations
~10 nM (cells), 1-10 μM (cornea), ~100 μM (oral mice). Adjust based on pilot data.
Instrument Outputs
NF-κB reporters, IκB-α westerns, qPCR/ELISA for IL-8, TNF-α, IL-6.
Control for MCR Pathways
Include α-MSH (positive control) and receptor antagonists to clarify MCR-independent activity.
Confirm PepT1 Dependence
Use PepT1 inhibitors or knockdown in gut models to verify transporter-mediated mechanism.
Comparison
KPV excels when NF-κB–dominant epithelial inflammation and non-pigmenting action are priorities. BPC-157 and TB-500 show broader pro-healing/angiogenic signals.
KPV
PepT1-facilitated epithelial uptake. MCR-independent in gut. Colitis ↓, keratinocyte NF-κB ↓, corneal healing ↑. Limited human trials.
BPC-157
Broad cytoprotection. NO modulation; GI tract, skin, tendon, nerve (preclinical breadth). Large preclinical body; limited human clinical.
TB-500
Actin-binding, angiogenesis. Robust dermal & corneal data. Selected clinical explorations in eye/wounds. Not melanotropic.
Best choice? If your primary endpoint is NF-κB–driven epithelial inflammation with a cosmetic constraint (non-pigmenting), KPV is the targeted pick. For broad wound angiogenesis/vascular stability, BPC-157 or TB-500 often make more sense.
FAQ
Bottom line: KPV is a transporter-savvy, non-pigmenting tripeptide that quiets epithelial NF-κB signaling — making it a precise tool for gut, skin, and corneal inflammation research. Its PepT1-mediated uptake and MCR-independent action distinguish it from full-length α-MSH. The combination of route + target + cosmetic neutrality is its distinctive research value.