KPV — Research Dossier
Evidence grading
Sequence
Lys-Pro-Val
α-MSH C-terminal tripeptide (positions 11–13); CAS 67727-97-3
Mechanism
NF-κB inhibition
Via PepT1 transporter; receptor-independent intracellular action
Tanning/appetite effects
None
Lacks the melanocortin receptor binding of parent α-MSH
Human efficacy trials
0
Consistent preclinical data; no completed human efficacy studies
KPV is the minimal anti-inflammatory sequence of alpha-MSH — mechanistically clean, receptor-independent, well-defined in animal models — with no human efficacy trials behind it yet.
KPV (Lys-Pro-Val) is the C-terminal tripeptide of α-MSH (positions 11–13), a 13-amino-acid neuropeptide that acts as an endogenous counter-regulatory anti-inflammatory signal. KPV retains α-MSH's anti-inflammatory activity while lacking the parent hormone's pigmentation and appetite effects — a clean separation that makes it a useful research tool for studying NF-κB-mediated inflammation without melanocortin-receptor confounds.
Its defining mechanistic feature is receptor independence: unlike α-MSH, KPV does not bind melanocortin receptors. Instead it is taken up into cells via the PepT1 transporter — notably in intestinal epithelium — and inhibits NF-κB signalling intracellularly. This mechanism is relevant for understanding its consistent activity in gut and dermal inflammation models.
“KPV reduces NF-κB nuclear translocation by up to approximately 80% in some models, acting through the PepT1 transporter rather than melanocortin receptors — a receptor-independent intracellular mechanism that explains its activity in intestinal inflammation without the pigmentation effects of parent α-MSH.”
— Dalmasso G et al., Gastroenterology 2008
Mechanism
KPV's defining feature is that it acts independently of melanocortin receptors. It is taken up into cells via the PepT1 transporter (notably in intestinal epithelium) and inhibits NF-κB signalling — a master regulator of inflammatory gene expression — by interfering with IκB kinase, reducing NF-κB nuclear translocation (reported up to approximately 80% in some models). This receptor-independent, intracellular mechanism explains its activity across diverse inflammatory contexts and its suitability for oral or local delivery strategies.
By acting downstream of the melanocortin receptor, KPV avoids the pigmentation effects and appetite signalling of α-MSH while preserving the anti-inflammatory activity encoded in the C-terminal sequence.
Evidence base
The preclinical evidence is consistent across several independent research groups:
- IBD models: Kannengiesser et al. (2008, Inflamm Bowel Dis) showed KPV reduced colonic damage and inflammatory cytokines in two distinct murine IBD models.
- PepT1-mediated uptake: Dalmasso et al. (2008, Gastroenterology) confirmed PepT1-dependent intestinal uptake and anti-inflammatory activity.
- Colitis-associated cancer: A 2016 study (Cell Mol Gastroenterol Hepatol) found KPV reduced colonic tumorigenesis in mice; the effect was abolished in PepT1-knockout animals, confirming the PepT1-dependence of the mechanism.
- Targeted delivery: Xiao et al. (2017, Biomaterials) developed hyaluronic-acid-functionalised nanoparticles for targeted KPV delivery to inflamed colon.
- Activity also reported in contact dermatitis and bronchial-inflammation models.
There are no completed human efficacy trials for KPV.
Regulatory status
Not approved by the FDA, MHRA, or EMA for any indication. Material supplied for laboratory work is research-use-only. Evidence grade: preclinical — a well-characterised, receptor-independent anti-inflammatory mechanism with coherent animal data across colitis, colitis-associated cancer, and dermatitis models, but no human efficacy evidence.
Nexyra Lab Catalogue
This dossier covers published clinical research on KPV. Nexyra Lab supplies research-grade KPV for in vitro laboratory use.
View KPV in the Nexyra catalogue (research use only) →See also
References
- 1
Kannengiesser K, et al. Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease Inflamm Bowel Dis 2008.
- 2
Dalmasso G, et al. PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation Gastroenterology 2008.
- 3
Xiao B, et al. Hyaluronic-acid-functionalised nanoparticles for targeted KPV delivery to inflamed colon Biomaterials 2017.
- 4
Laroui H, et al. Reduced colonic tumorigenesis by KPV in a PepT1-dependent manner (colitis-associated cancer model) Cell Mol Gastroenterol Hepatol 2016.
Research & Laboratory Use Only
This dossier is compiled for research planning and educational purposes only. It summarises published scientific literature and does not constitute medical advice, dosing guidance, or a therapeutic claim. All Nexyra Lab products are for research purposes only and are not for human or veterinary use. Nothing in this document should be interpreted as recommending, endorsing, or facilitating the self-administration of any compound.
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