What Is KPV?
KPV (Lys-Pro-Val) is a synthetic tripeptide made of three amino acids. It corresponds to residues 11 to 13 at the C-terminus of alpha-melanocyte-stimulating hormone (alpha-MSH), a 13-residue neuropeptide derived from proopiomelanocortin (POMC) with both pigmentary and anti-inflammatory activity. Classic structure-activity work isolated much of alpha-MSH's anti-inflammatory activity to this C-terminal tripeptide, separate from the melanotropic (pigment-stimulating) portion of the molecule.
Because it carries the anti-inflammatory signature of alpha-MSH without the hormone's pigmentary effect, KPV has been studied as a distinct research compound. The largest and most consistent body of published work examines KPV in preclinical models of intestinal inflammation, where its uptake through the peptide transporter PepT1 provides a route into inflamed epithelial tissue. KPV is a research compound and is not an approved drug for any use.
Peptide Profile
Full Name: Lysine-Proline-Valine tripeptide
Sequence: Lys-Pro-Val (K-P-V)
Molecular Formula: C16H30N4O4
Molecular Weight: ~342.4 g/mol
CAS Number: 67727-97-3
Origin: C-terminal fragment (residues 11-13) of alpha-MSH
Mechanism of Action
KPV's most consistently reported activity in the literature is anti-inflammatory signaling that does not require melanocortin-receptor binding. Research has identified several intracellular pathways through which it appears to act.
NF-kB Pathway Modulation
The most consistently reported mechanism is suppression of nuclear factor-kB (NF-kB) signaling. In stimulated intestinal epithelial and immune cells, research indicates KPV reduces NF-kB nuclear translocation and the downstream transcription of pro-inflammatory mediators, lowering output of cytokines such as TNF-alpha, IL-1beta, IL-6, and IL-8 in preclinical models.
Melanocortin-Receptor-Independent Action
A distinguishing feature reported in the primary literature is that KPV's anti-inflammatory action does not require melanocortin-receptor binding or elevation of cAMP. Studies of melanocortin peptides in macrophages describe a receptor-independent, intracellular route of NF-kB inhibition, and for the short KPV fragment this arm predominates, which is why it lacks the pigmentary and hormonal effects of the parent hormone.
PepT1-Mediated Cellular Uptake
KPV is a substrate of the di/tripeptide transporter PepT1 (SLC15A1), which is expressed by intestinal epithelial cells and is upregulated in inflamed intestinal tissue. Research has shown KPV is carried into colonocytes via PepT1, where it acts intracellularly to blunt NF-kB and MAP-kinase signaling, meaning it acts inside the cell rather than only at surface receptors.
Direct Antimicrobial Activity
Independent of the anti-inflammatory pathways, alpha-MSH and its C-terminal fragments including KPV have shown direct antimicrobial activity in vitro against organisms such as Staphylococcus aureus and Candida albicans. This is a distinct, pathogen-directed activity rather than a host-signaling effect.
Research Overview
The KPV literature is focused rather than broad, and is strongest in the intestinal-inflammation domain. The following table summarizes key published research areas.
| Research Area | Key Findings | Study Type |
|---|---|---|
| Inflammatory Bowel / Colitis | Studies observed that oral or luminal KPV reduced chemically-induced colonic inflammation in mice, acting through PepT1-mediated uptake into colonocytes | In vivo (rodent) + in vitro |
| Disease Recovery (IBD) | In murine colitis models, KPV treatment was associated with earlier recovery and stronger body-weight regain versus controls | In vivo (rodent) |
| Targeted Delivery | Orally administered hyaluronic-acid-functionalized nanoparticles loading KPV alleviated ulcerative-colitis features in mice more efficiently than free peptide | In vivo (rodent) |
| Antimicrobial Activity | Alpha-MSH and its C-terminal KPV fragment inhibited growth of S. aureus and C. albicans in culture across a broad concentration range | In vitro |
| NF-kB / Cytokine Modulation | Melanocortin peptides suppressed stimulus-induced NF-kB DNA binding and nitric oxide production in macrophages via a cAMP-independent route | In vitro |
| Non-Pigmentary Anti-Inflammatory Activity | Reviews of alpha-MSH-derived tripeptides document anti-inflammatory and protective effects without pigmentary action, including contact-hypersensitivity models | Review of in vitro / in vivo |
The strongest KPV-specific evidence sits in the intestinal-inflammation and drug-delivery domains. Some effects frequently attributed to KPV on vendor pages, such as broad wound-healing or mast-cell claims, are better supported for the parent hormone alpha-MSH than for the KPV tripeptide itself. The KPV literature is preclinical: no completed human clinical trials establish safety or efficacy.
Common Areas of Research Interest
Scientific interest in KPV concentrates in a few well-defined domains where the tripeptide-specific literature is strongest.
- Intestinal inflammation and IBD models, the best-developed KPV literature, where PepT1-mediated uptake gives a rationale for oral, gut-targeted delivery
- Targeted oral drug-delivery systems, KPV is a recurring model cargo for PepT1-targeted and nanoparticle delivery aimed at inflamed colonic tissue
- Non-pigmentary anti-inflammatory signaling, interest centers on separating alpha-MSH's anti-inflammatory activity from its melanotropic and hormonal effects
- Cutaneous inflammation, explored preclinically in skin-inflammation and contact-hypersensitivity contexts, reflecting the parent hormone's skin biology
- Antimicrobial peptide research, KPV's direct activity against bacteria and yeast positions it within host-defense-peptide investigation
- Mechanism dissection, used as a tool to probe intracellular, receptor-independent control of NF-kB and MAPK inflammatory signaling
Pharmacokinetics
Formal human pharmacokinetic data for KPV are absent, and the parameters below are inferred from preclinical work and general peptide chemistry rather than measured in humans.
As a very small linear tripeptide, KPV is a defined substrate of the PepT1 transporter, giving it an active route into epithelial and some immune cells that is relevant to oral and gut-local delivery research. Because its anti-inflammatory activity does not depend on melanocortin-receptor occupancy, classic receptor-occupancy PK/PD models do not straightforwardly apply.
No published half-life, Cmax, AUC, oral-bioavailability, or human dosing data exist for KPV. As a small linear peptide it is expected to be susceptible to peptidase degradation, implying a short residence time, which is part of the rationale for the nanoparticle and carrier-based delivery approaches seen in the literature.
Comparison to Similar Peptides
KPV is often discussed alongside its parent hormone and other peptides studied in anti-inflammatory or tissue-repair contexts.
| Feature | KPV | Alpha-MSH | BPC-157 |
|---|---|---|---|
| Origin | C-terminal tripeptide of alpha-MSH | POMC-derived endogenous neuropeptide | Peptide derived from human gastric juice protein |
| Primary Research Focus | Intestinal inflammation, targeted delivery | Pigmentation, energy balance, broad immunomodulation | Preclinical tissue and gastrointestinal repair |
| Amino Acids | 3 (~342 Da) | 13 (~1,665 Da) | 15 (~1,419 Da) |
| Key Mechanism | Receptor-independent NF-kB/MAPK suppression; PepT1 uptake | MC1-MC5 receptor agonism plus receptor-independent arm | Proposed angiogenic and nitric-oxide-pathway effects |
| Research Volume | Modest, focused (colitis, delivery) | Large, decades-deep | Moderate, almost entirely preclinical |
Frequently Asked Questions
Sources & References
- Dalmasso G, Charrier-Hisamuddin L, Nguyen HT, et al. "PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation." Gastroenterology. 2008;134(1):166-78. PubMed
- Kannengiesser K, Maaser C, Heidemann J, et al. "Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease." Inflamm Bowel Dis. 2008;14(3):324-31. PubMed
- Xiao B, Xu Z, Viennois E, et al. "Orally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis." Mol Ther. 2017;25(7):1628-1640. PubMed
- Cutuli M, Cristiani S, Lipton JM, Catania A. "Antimicrobial effects of alpha-MSH peptides." J Leukoc Biol. 2000;67(2):233-9. PubMed
- Brzoska T, Luger TA, Maaser C, et al. "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." Endocr Rev. 2008;29(5):581-602. PubMed
- Mandrika I, Muceniece R, Wikberg JE. "Effects of melanocortin peptides on lipopolysaccharide/interferon-gamma-induced NF-kappaB DNA binding and nitric oxide production in macrophage-like RAW 264.7 cells: evidence for dual mechanisms of action." Biochem Pharmacol. 2001;61(5):613-21. PubMed
- Hiltz ME, Lipton JM. "Antiinflammatory activity of a COOH-terminal fragment of the neuropeptide alpha-MSH." FASEB J. 1989;3(11):2282-4. PubMed
- Catania A, Gatti S, Colombo G, Lipton JM. "Targeting melanocortin receptors as a novel strategy to control inflammation." Pharmacol Rev. 2004;56(1):1-29. PubMed
Explore KPV
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