KPV is a tripeptide (Lys-Pro-Val) that corresponds to the last three amino acids of α-melanocyte-stimulating hormone (α-MSH). It has drawn research interest because it keeps much of the anti-inflammatory activity of the parent hormone without its pigmentary effects. Most published work focuses on epithelial cells of the gut and airway, where KPV inhibits the NF-κB inflammatory pathway. This guide summarizes how KPV gets into cells, what it does once there, the main experimental models, and how it fits into the KLOW research blend.
KPV is supplied by BioSim for laboratory research only. It is not for human or veterinary use, and nothing here is guidance on administration to people or animals.
From α-MSH to KPV
α-MSH is a 13-amino-acid peptide derived from proopiomelanocortin (POMC). Besides its role in pigmentation, it has potent anti-inflammatory and protective effects. These act through melanocortin receptors in the brain and on immune and non-immune cells, and involve pathways including NF-κB activation, adhesion molecule expression, pro-inflammatory cytokine production, IL-10 synthesis and T cell activity (Brzoska et al., 2008).
The pigmentary effect of α-MSH is an obstacle for research focused on inflammation. Its C-terminal tripeptide, KPV (α-MSH 11-13), retains anti-inflammatory activity but lacks the pigmentary action, and has been studied as an alternative for that reason (Brzoska et al., 2008).
How KPV Enters Cells: PepT1
KPV is small enough to be carried by peptide transporters. In human intestinal epithelial cell lines (Caco2-BBE and HT29-Cl.19A) and human T cells (Jurkat), uptake experiments showed that KPV is transported by PepT1, the proton-coupled di- and tripeptide transporter expressed in intestinal epithelium and some immune cells (Dalmasso et al., 2008). This uptake route is part of what makes KPV interesting: it can act inside the cell rather than only at a surface receptor.
Mechanism: Inhibiting NF-κB
NF-κB is a family of transcription factors that controls many pro-inflammatory genes. In resting cells it is held in the cytoplasm by the inhibitor IκBα. Inflammatory signals trigger IκBα degradation, freeing the p65 (RelA) subunit to enter the nucleus and switch on cytokine and chemokine genes.
Two studies define how KPV acts on this pathway:
- Intestinal and immune cells. Nanomolar concentrations of KPV inhibited NF-κB and MAP kinase inflammatory signaling and reduced pro-inflammatory cytokine secretion in cells stimulated with pro-inflammatory cytokines (Dalmasso et al., 2008).
- Airway epithelium. In immortalized human bronchial epithelial cells (16HBE14o-), KPV produced a concentration-dependent inhibition of TNFα- and virus-evoked NF-κB signaling, matrix metalloproteinase-9 activity, and IL-8 and eotaxin secretion. The effect was associated with nuclear import of KPV, stabilization of IκBα and reduced nuclear translocation of p65. Competition assays pointed to an interaction between KPV and the importin-α3 binding site on p65 (Land, 2012).
The same airway study compared KPV with γ-MSH, whose anti-inflammatory effect required the melanocortin 3 receptor. KPV’s effect, by contrast, was linked to its intracellular action on p65 nuclear import (Land, 2012).
Animal Models: Experimental Colitis
KPV has been tested mainly in mouse colitis models:
- DSS and TNBS colitis. KPV given in drinking water reduced the incidence of DSS- and TNBS-induced colitis, with lower pro-inflammatory cytokine expression (Dalmasso et al., 2008).
- DSS and transfer colitis, with MC1R-deficient mice. In DSS colitis, KPV led to earlier recovery and reduced inflammatory infiltrates and myeloperoxidase activity in colonic tissue. Similar effects were seen in CD45RBhi transfer colitis. In mice with a nonfunctional melanocortin 1 receptor, KPV rescued all animals in the group from death during DSS colitis, suggesting its effects are at least partly independent of MC1R signaling (Kannengiesser et al., 2008).
- Targeted delivery. KPV loaded into hyaluronic acid-functionalized polymeric nanoparticles was delivered to colonic epithelial cells and macrophages. In a mouse colitis model, the nanoparticles in a chitosan/alginate hydrogel reduced mucosal damage and TNF-α more than a non-targeted system (Xiao et al., 2017).
| Model | Main finding | Reference |
|---|---|---|
| Caco2-BBE, HT29, Jurkat cells | PepT1-mediated uptake; nanomolar inhibition of NF-κB and MAPK | Dalmasso et al., 2008 |
| 16HBE14o- bronchial epithelial cells | IκBα stabilization; blocked p65 nuclear import | Land, 2012 |
| DSS and TNBS colitis (mouse) | Reduced colitis incidence and cytokine expression | Dalmasso et al., 2008 |
| DSS and transfer colitis, MC1R-deficient mice | Effects partly independent of MC1R | Kannengiesser et al., 2008 |
| HA-nanoparticle delivery (mouse) | Targeted delivery to colonic cells; reduced TNF-α | Xiao et al., 2017 |
KPV in the KLOW Research Blend
BioSim’s KLOW 80mg blend combines four research compounds in one vial: KPV 10mg, BPC-157 10mg, TB-500 10mg and GHK-Cu 50mg. Labs use blends like this in tissue repair and inflammation models where several pathways are studied together. KPV contributes the NF-κB-focused anti-inflammatory component described above.
When using a blend, interpret results with care. Effects cannot be assigned to any single component unless the design includes arms with each compound alone. A typical approach is to run the blend alongside KPV alone and the other components alone at matched amounts. For background on the other compounds, see our tissue repair research overview, the BPC-157 research guide and the GHK-Cu research guide.
Experimental Design Notes
- Confirm the uptake route. PepT1 expression varies between cell types. Competition with a known PepT1 substrate can test whether uptake depends on it (Dalmasso et al., 2008).
- Measure pathway endpoints. NF-κB reporter assays, IκBα levels, p65 nuclear localization and cytokine secretion all match the proposed mechanism (Land, 2012).
- Test receptor independence. MC1R-deficient models help separate melanocortin receptor effects from intracellular actions (Kannengiesser et al., 2008).
More background is available in our overview of gastrointestinal barrier research and the Healing and Recovery category.
Handling in the Lab
KPV is supplied lyophilized. Reconstitute with a suitable sterile diluent, aliquot the stock, avoid repeated freeze-thaw cycles and store as labeled. See our storage and stability guide.
Frequently Asked Questions
Does KPV act through melanocortin receptors?
Evidence suggests its effects are at least partly independent of MC1R (Kannengiesser et al., 2008), and in epithelial cells it acts intracellularly after PepT1 uptake (Dalmasso et al., 2008; Land, 2012).
Why use KPV instead of α-MSH?
KPV retains anti-inflammatory activity but lacks the pigmentary action of the full hormone (Brzoska et al., 2008).
How do I confirm the identity of my lot?
Every BioSim lot is third-party tested, with identity confirmed by mass spectrometry. Available certificates are published on our COA page.
References
- Brzoska T, Luger TA, Maaser C, et al. (2008). 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. Endocrine reviews, 29(5), 581-602. PMID: 18612139 · DOI: 10.1210/er.2007-0027
- Dalmasso G, Charrier-Hisamuddin L, Nguyen HT, et al. (2008). PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation. Gastroenterology, 134(1), 166-78. PMID: 18061177 · DOI: 10.1053/j.gastro.2007.10.026
- Kannengiesser K, Maaser C, Heidemann J, et al. (2008). Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease. Inflammatory bowel diseases, 14(3), 324-31. PMID: 18092346 · DOI: 10.1002/ibd.20334
- Land SC (2012). Inhibition of cellular and systemic inflammation cues in human bronchial epithelial cells by melanocortin-related peptides: mechanism of KPV action and a role for MC3R agonists. International journal of physiology, pathophysiology and pharmacology, 4(2), 59-73. PMID: 22837805
- Xiao B, Xu Z, Viennois E, et al. (2017). Orally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis. Molecular therapy : the journal of the American Society of Gene Therapy, 25(7), 1628-1640. PMID: 28143741 · DOI: 10.1016/j.ymthe.2016.11.020
Research These Compounds: KPV 10mg, the KLOW 80mg blend and BPC-157 10mg from BioSim Peptides: 99%+ purity, every lot third-party tested with identity confirmed by mass spectrometry, and available certificates published on our COA page. For laboratory research use only. Not for human consumption.
