Abstract
KPV (Lys-Pro-Val; also described as α-MSH(11–13)) is a melanocortin-derived tripeptide with reproducible anti-inflammatory and tissue-protective effects in vitro and in vivo. Importantly for gastrointestinal applications, KPV can be transported across intestinal epithelia via the proton-coupled oligopeptide transporter PepT1, enabling oral administration to reduce inflammation in models of colitis. Recent work has focused on improving oral stability and targeted colonic delivery using nanoparticle and polymer carriers. This paper summarizes chemical identity, mechanisms of action, evidence for oral efficacy, formulation strategies, safety/handling, and relevant literature. PMC+1
Chemical identity & catalog information
- Common name: KPV (Lys-Pro-Val) — also listed as α-MSH(11–13) or ACTH(11–13) in some supplies.
- Sequence: L-Lysyl-L-prolyl-L-valine (Lys-Pro-Val).
- CAS number (commonly cited): 67727-97-3. PARTICLE, s. r. o.+1
- Molecular formula / mass (typical listing): C₁₆H₃₀N₄O₄; ≈342.43 g·mol⁻¹ (salt forms vary). PARTICLE, s. r. o.
- Form: white powder (free base or acetate salt) in research catalogs (purity specifications vary by vendor). PARTICLE, s. r. o.
Biological background & rationale for oral use
KPV is the C-terminal tripeptide of α-melanocyte-stimulating hormone (α-MSH) and retains anti-inflammatory and pro-healing activity in multiple models. Because KPV is a di/tripeptide compatible with intestinal oligopeptide transport systems (notably PepT1), it can be taken up across the gut epithelium and exert local (and potentially systemic) effects following oral administration. This transporter-mediated uptake partly explains the peptide’s activity in oral dosing studies for intestinal inflammation. PMC+1
Load-bearing evidence: PepT1-dependent intestinal uptake of KPV reduced disease activity in murine colitis models (DSS and TNBS), and PepT1 expression modulates KPV’s protective effects. PMC+1
Mechanisms of action (research overview)
- Melanocortin-related signaling and anti-inflammatory action: KPV modulates inflammatory signaling (including NF-κB pathways) and can reduce pro-inflammatory cytokines in cellular and animal models; some actions are independent of classical melanocortin receptor signaling, indicating multiple mechanisms may be involved. PMC+1
- PepT1-mediated uptake for oral bioavailability: PepT1 (SLC15A1) — a proton-coupled oligopeptide transporter expressed in small intestinal epithelia and induced in inflamed colon — transports KPV into target cells, enabling therapeutic concentrations at the mucosa after oral dosing. PMC+1
- Direct tissue protective effects: KPV has been reported to accelerate mucosal healing, reduce leukocyte infiltration, and support epithelial barrier integrity in gut inflammation models. PubMed+1
Key preclinical and translational evidence (selected studies)
- Dalmasso et al., 2007 — PepT1-Mediated Uptake & Colitis Models. Demonstrated that orally administered KPV reduces severity of DSS- and TNBS-induced colitis in mice and that PepT1 mediates uptake into epithelial cells. This is a cornerstone paper for oral KPV research. PMC+1
- Kannengiesser et al., 2008 — Murine Colitis Models. Reported significant anti-inflammatory effects of KPV in two murine colitis models, supporting the peptide’s therapeutic potential in gastrointestinal inflammation. PubMed
- Xiao et al., 2017 — Oral targeting with HA-KPV nanoparticles. Developed hyaluronic-acid–based nanoparticles for oral delivery of KPV, demonstrating targeted colonic delivery, mucosal healing, and reduced inflammation in ulcerative-colitis models — illustrating advanced formulation strategies to improve oral performance. PMC
- Viennois et al., 2016 — PepT1, KPV and colitis-associated carcinogenesis. Explored PepT1’s role in colitis-associated tumorigenesis and showed KPV’s protective effects were PepT1-dependent in certain models. PMC+1
Oral delivery challenges & formulation strategies
Oral peptides face enzymatic degradation, low mucosal residence, and variable uptake. For KPV, several strategies have been investigated:
- Exploitation of PepT1: KPV’s native size and sequence are compatible with PepT1 transport; inflammation upregulates PepT1 in colon, which can increase local uptake. PMC
- Nanoparticle / polymer carriers: Hyaluronic-acid nanoparticles (HA-KPV NPs) and other mucoadhesive carriers protect KPV from proteolysis, increase mucosal residence, and target delivery to inflamed colon segments. These carriers demonstrated enhanced efficacy in animal ulcerative colitis models. PMC
- Enteric coatings and pro-drugs: Enteric capsules, pH-sensitive polymers, or pro-peptide designs can help bypass gastric degradation and release KPV in the small intestine/colon. (Formulation work is ongoing and application-specific.) PMC+1
Safety, limitations, and regulatory status
- Preclinical safety: Published animal studies and nanoparticle formulations generally report favorable tolerability at experimentally used doses with no major acute toxicities described; however, systematic toxicology packages for oral KPV in humans are limited. PMC+1
- Human data: Robust human clinical trials for oral KPV are lacking. Most evidence is preclinical (cell lines, rodents) or from ex-vivo tissues. Translation to human therapy requires controlled clinical studies and regulatory review. PMC+1
- Research use only: KPV is sold by research suppliers for laboratory use (CAS 67727-97-3) and should not be used in humans outside approved clinical trials. Always follow institutional and regulatory guidelines. PARTICLE, s. r. o.
Practical lab handling & storage (research context)
- Typical storage: lyophilized powder stored at −20 °C (desiccated) is common; aqueous solutions are usually prepared fresh or stored frozen per vendor SDS. Check the supplier’s certificate of analysis (CoA) for exact recommendations. PARTICLE, s. r. o.+1
- Solubility: water, buffered saline, or bacteriostatic water; salt form (acetate) affects solubility.
- Safety: use PPE, avoid ingestion or unapproved human exposure, and comply with institutional biosafety and chemical handling policies.
Representative references / PubMed / PMC links
(Selected, high-relevance publications — click to open)
- Dalmasso G, et al. PepT1-Mediated Tripeptide KPV Uptake Reduces Intestinal Inflammation. Gastroenterology / PMC version. 2007–2008. PMC+1
- Xiao B, et al. Orally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Based Nanoparticles. Sci Rep. 2017. PMC. PMC
- Kannengiesser K, et al. Melanocortin-derived tripeptide KPV has anti-inflammatory effects in murine colitis models. PubMed. 2008. PubMed
- Viennois E, et al. Critical role of PepT1 in promoting colitis-associated carcinogenesis and KPV modulatory studies. PubMed / SciDirect. 2016. PMC+1
- Review — α-MSH and related peptides: anti-inflammatory and protective properties (relevant background). PubMed+1
10 Frequently Asked Questions (FAQ)
1) What is “oral KPV”?
Oral KPV refers to administration of the tripeptide Lys-Pro-Val by mouth, relying on intestinal uptake (notably via PepT1) and/or protective formulations to reach the gut mucosa and exert anti-inflammatory actions. PMC+1
2) What is the CAS number for KPV?
The commonly cited CAS number for KPV (α-MSH 11–13; Lys-Pro-Val) is 67727-97-3. PARTICLE, s. r. o.+1
3) Is there evidence that orally administered KPV works?
Yes — multiple preclinical studies show that orally delivered KPV reduces inflammation and improves mucosal healing in rodent colitis models; PepT1-dependent uptake is a key mechanism. However, human clinical data are currently very limited. PMC+1
4) How is oral KPV protected from digestion?
Researchers use strategies like nanoparticle encapsulation (e.g., hyaluronic-acid nanoparticles), enteric coatings, mucoadhesive polymers, or pro-drug approaches to protect KPV from proteolysis and enhance delivery to the small intestine/colon. PMC
5) Why is PepT1 important for oral KPV?
PepT1 (SLC15A1) transports di- and tripeptides across intestinal epithelial cells. KPV is a substrate for PepT1, which facilitates cellular uptake and local mucosal concentrations after oral dosing. PepT1 expression is often upregulated in inflamed colon, enhancing uptake in disease states. PMC+1
6) Are there human clinical trials?
As of the cited literature, robust, large-scale human clinical trials for oral KPV are lacking. Most evidence derives from animal models and in-vitro/ex-vivo work or formulation studies. Clinical translation is an active area for future research. PMC+1
7) What are the main therapeutic indications studied preclinically?
Ulcerative colitis and other inflammatory bowel disease (IBD) models, mucosal healing and anti-inflammatory applications, and investigations into prevention of colitis-associated tumorigenesis in rodent models. PMC+1
8) How is KPV supplied for research and how should it be stored?
Vendors supply KPV as lyophilized powder (free acid or salt). Typical storage is −20 °C, protected from moisture; check vendor SDS/CoA for specifics. PARTICLE, s. r. o.+1
9) Is KPV safe?
Preclinical tolerability in published studies is generally acceptable at experimental doses, but systematic human safety and toxicology data for oral KPV are limited. Do not use in humans outside approved protocols. PMC+1
10) What are promising formulation approaches for oral delivery?
Hyaluronic-acid nanoparticles, mucoadhesive or enteric polymer systems, and PepT1-exploiting delivery strategies have shown promise in preclinical studies to improve stability, targeting, and efficacy. PMC+1
Conclusions & research gaps
KPV is a small, biologically active peptide with strong preclinical evidence for anti-inflammatory and mucosal-healing effects. The peptide’s compatibility with intestinal peptide transporters (PepT1) makes oral delivery feasible, and nanoparticle/targeted formulations further improve local efficacy in animal models. Key gaps remain in systematic toxicology, scaleable GMP production standards for oral formulations, and — crucially — human clinical trial data. Future work should prioritize well-designed translational studies to evaluate safety, dosing, and efficacy in humans. PMC+1
Disclaimer
This document is for research and informational purposes only. KPV and related formulations are for laboratory research use only unless evaluated and approved through appropriate regulatory/clinical pathways. Do not use research peptides for human or veterinary treatment outside of approved clinical trials.
