KPV

preclinical

Also known as: Lysine-Proline-Valine, α-MSH (11-13)

**Mechanism of Action** KPV (Lysine-Proline-Valine), the C-terminal tripeptide of α-melanocyte-stimulating hormone (α-MSH 11-13), exerts anti-inflammatory effects primarily through PepT1-mediated cellular uptake. Once internalized, it inhibits nuclear factor-κB (NF-κB) activation, reducing pro-inflammatory cytokine production (e.g., TNF-α, IL-1β, IL-6). This pathway is particularly relevant in intestinal epithelial cells and immune cells, where KPV modulates oxidative stress and apoptosis. **Key Research Findings** Preclinical studies in inflammatory bowel disease (IBD) models (e.g., DSS-induced colitis in mice) demonstrate that KPV reduces colonic inflammation, mucosal damage, and neutrophil infiltration. It also enhances tight junction protein expression (e.g., occludin, ZO-1), improving intestinal barrier integrity. In vitro, KPV suppresses LPS-induced NF-κB signaling in Caco-2 cells and macrophages. Notably, its effects are dose-dependent and require PepT1 expression, as PepT1 knockout models show diminished efficacy. **Clinical Relevance** KPV remains in preclinical development, with no human trials reported. Its potential lies in targeted therapy for IBD, particularly ulcerative colitis and Crohn’s disease, where PepT1 is upregulated in inflamed tissue. However, challenges include rapid enzymatic degradation and limited oral bioavailability. Future research may focus on formulation strategies (e.g., nanoparticle encapsulation) to enhance stability and delivery. For research purposes only — not medical advice.

Key data

Category
Healing & Recovery
Molecular weight
192.21 g/mol
Molecular formula
C11H12O3
CAS number
88768-11-0
Administration
oral, subcutaneous, topical
Research status
preclinical
References
89
Tags
anti-inflammatory, gut-health, melanocortin

Research & studies

A new era of doping? Use of peptide and peptide-analog drugs in recreational and professional sport and bodybuilding: a critical review
The Journal of sports medicine and physical fitness · 2026 · PubMed

Peptides like growth hormone secretagogues and analogues are marketed for muscle growth and recovery but lack clinical evidence for supraphysiological use.; Potential risks include cardiovascular strain, insulin resistance, dyslipidemia, and psychiatric instability.; Unregulated supply chains lead to mislabeled or contaminated products, exacerbating health dangers.; Prevalence data on recreational use, especially among younger individuals, is critically lacking.

Lysine-proline-valine peptide attenuates hepatic lipid accumulation through ROS-dependent regulation of the PPARγ pathway in HepG2 cells
Cytotechnology · 2026 · PubMed
NLRP3 autophagic degradation disruption in melanocytes contributes to vitiligo development
Cell death and differentiation · 2026 · PubMed

NLRP3 expression is significantly increased in melanocytes of vitiligo patients and melanoma-Treg-induced vitiligo mice.; Knockout of NLRP3 effectively alleviates vitiligo progression in the mouse model.; Downregulation of β-TrCP1 reduces K27-linked ubiquitination of NLRP3, weakening its interaction with autophagy receptor NDP52 and impairing selective autophagic degradation.; Melanocyte-specific knockdown of NLRP3 using KPV-Lipos with Nlrp3 shRNA significantly alleviates vitiligo development.

Inflammation-triggered self-immolative conjugates enable oral peptide delivery by overcoming gastrointestinal barriers
Science advances · 2026 · PubMed

SIPPC platform integrates PEG, ROS-responsive self-immolative module, and hydrolyzable scaffold to form nanoparticles with GI stability and mucus penetration.; proKPV achieved 3.8-fold higher colonic accumulation than free KPV in colitis mice, with efficacy at a 20-fold lower dose.; Oral proKPV accumulated in inflamed lungs and showed potent anti-inflammatory efficacy in acute lung injury mice.; Ac-QAW and IRW-based conjugates showed comparable benefits, supporting SIPPC as a general platform for oral peptide delivery.

Host defense peptides as a new drug lead to a strategy for inflammatory bowel disease
Drug discovery today · 2025 · PubMed
Exploring the Role of Tripeptides in Wound Healing and Skin Regeneration: A Comprehensive Review
International journal of medical sciences · 2025 · PubMed
Lysine-Proline-Valine peptide mitigates fine dust-induced keratinocyte apoptosis and inflammation by regulating oxidative stress and modulating the MAPK/NF-κB pathway
Tissue & cell · 2025 · PubMed

PM10 exposure suppressed HaCaT cell proliferation and induced IL-1 secretion.; KPV (50 μg/mL) restored cell viability and reduced IL-1 secretion in PM10-treated cells.; KPV inhibited ROS production and suppressed MAPK (ERK, p38) activation and NF-κB signaling.; KPV decreased apoptosis-related proteins (Bax, Bcl-2, cleaved caspase-3) and blocked ROS-mediated caspase-1 activation, reducing IL-1 secretion.

Multicompartmental Hydrogel Microspheres with a Concentric Thin Oil Layer: Protecting and Targeting Therapeutic Agents for Inflammatory Bowel Disease
ACS applied bio materials · 2025 · PubMed

The oil layer protects encapsulated materials from the acidic stomach environment during digestion.; Hydrogel cores provide high stability under high osmolarity conditions in the stomach.; Fine-tuning the shell composition enables selective release in response to gut pH conditions.; The system preserves anti-inflammatory activities of 5-ASA and KPV and their effects on colonic epithelial cell migration and proliferation.

Frequently asked questions

What is KPV?

**Mechanism of Action** KPV (Lysine-Proline-Valine), the C-terminal tripeptide of α-melanocyte-stimulating hormone (α-MSH 11-13), exerts anti-inflammatory effects primarily through PepT1-mediated cellular uptake. Once internalized, it inhibits nuclear factor-κB (NF-κB) activation, reducing pro-inflammatory cytokine pro

How does KPV work?

C-terminal tripeptide of α-MSH with anti-inflammatory action via PepT1 uptake and NF-κB inhibition, studied in IBD models.

What is the research status of KPV?

KPV is currently classified as preclinical, with 89 research references on record. This is for research purposes only and is not medical advice.

What is the molecular weight of KPV?

KPV has a molecular weight of approximately 192.21 g/mol (formula C11H12O3).

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