KPV 5 MG

Description

KPV (ACTH(11-13), alpha-MSH)

KPV is a short peptide consisting of the amino acids lysine-proline-valine and represents the C-terminal fragment of alpha-melanocyte stimulating hormone (α-MSH). It is one of several α-MSH derivatives studied to evaluate whether they retain properties such as photoprotection, effects on ischemia, modulation of sexual function, or influence on feeding behavior and energy balance. Among these, KPV has shown notable anti-inflammatory effects. Current research is exploring its therapeutic potential, particularly in inflammatory bowel disease. Studies indicate that KPV may exert anti-inflammatory activity across multiple systems, including the central nervous system, gastrointestinal tract, lungs, vascular tissues, and joints. Due to its small size, KPV can be delivered through various routes, including oral, intravenous, and transdermal administration.

KPV Peptide Structure

Amino Acid Sequence: Lys-Pro-Val
Molecular Formula: C₁₆H₃₀N₄O₄
Molecular Weight: 342.43 g/mol
PubChem CID: 125672
CAS Number: 67727-97-3
Synonyms: MSH (11-13), ACTH(11-13), alpha-MSH(11-13)

Source: PubChem

KPV Peptide Research

One of the most significant findings from research on KPV is its ability to reduce intestinal inflammation. In mouse models of inflammatory bowel disease (IBD), KPV has been shown to decrease inflammatory cell infiltration, myeloperoxidase (MPO) activity, and overall histological signs of inflammation. Treated mice demonstrated faster recovery and greater weight gain compared to those receiving placebo [2].

Advances in delivery methods have involved loading KPV onto nanoparticles functionalized with hyaluronic acid, which helps target the peptide’s anti-inflammatory effects more precisely within the intestine. This targeted approach promotes faster mucosal healing and reduces inflammation by strongly downregulating TNF-alpha in these models [3]. This strategy allows KPV to effectively reduce inflammation in IBD while minimizing effects on TNF-alpha in other parts of the body.

Modifying KPV for improved oral bioavailability does not increase its intrinsic efficacy but enhances its potency, thereby reducing the total dose required to achieve therapeutic effects.

Source: PubChem

Research suggests that TNF-alpha is not the only inflammatory mediator that KPV has an impact on. The peptide also reduces NF-kappaB and mitogen-activated protein kinase activity. These effects work in tandem with TNF-alpha inhibition to reduce inflammatory changes in the intestine. Mice treated with KPV have substantially less colonic infiltration and normal colon lengths compared to controls[4].

Source: PubChem

Selective Activity of KPV in Inflamed Tissue

Research indicates that KPV primarily exerts its effects during conditions of excessive inflammation and has minimal impact on normal, healthy tissue. This selective action is partly due to KPV entering colonic cells via a transporter that is upregulated during inflammation. Specifically, Professor Didier Merlin’s work has identified PepT1, a protein channel expressed in significant amounts only in the intestine during inflammatory states, as the route for KPV cellular entry. This mechanism explains why KPV is more effective in inflamed tissue and suggests potential for KPV as a preventative or maintenance treatment in inflammatory bowel disease (IBD). Because KPV has little to no effect in quiescent periods, it may be safely taken continuously, remaining inactive until inflammation occurs and then being excreted once no longer needed.

This concept of targeting disease-associated proteins like PepT1, which are altered but not directly pathogenic, opens new possibilities for drug delivery. It could enable localized drug activity in diseased tissues, reducing required dosages and minimizing systemic side effects. Additionally, drugs that are not highly potent individually might still be highly effective when targeted in this manner.

KPV as a General Anti-Inflammatory

Research dating back to 1984 demonstrated that KPV has anti-inflammatory and anti-pyretic (fever-reducing) properties, although it showed lower potency compared to the full alpha-melanocyte stimulating hormone (α-MSH) molecule. This led scientists to investigate modified forms of α-MSH to improve therapeutic effects [5].

Studies have shown that α-MSH and its analogues reduce inflammation across a wide range of conditions, including fever, allergic contact dermatitis, vasculitis, fibrosis, arthritis, and inflammation in the eyes, brain, lungs, and gastrointestinal tract. While α-MSH is generally the most effective anti-inflammatory, it causes skin pigmentation as a side effect. KPV, in contrast, does not cause pigmentation, making it a safer alternative. Although KPV is slightly less potent, its favorable side effect profile means it can be administered at higher doses to achieve therapeutic effects [6].

Most of α-MSH’s anti-inflammatory activity is attributed to the KPV fragment. However, the full α-MSH molecule appears to be better at suppressing late-stage inflammatory responses. For example, in allergic contact dermatitis, α-MSH more effectively reduces swelling two weeks after exposure compared to KPV, suggesting that α-MSH may influence immune modulation mechanisms beyond the immediate inflammatory response [7]. Further research is ongoing to clarify these processes.

The accompanying graph illustrates ear swelling due to contact dermatitis at 24 hours and two weeks post-exposure. At 24 hours, co-administration of KPV with the irritant nearly matches the effectiveness of α-MSH. However, at two weeks, α-MSH demonstrates significantly greater reduction in swelling than KPV.

Source: PubChem

Wound Healing

Wound healing is a complex physiological process consisting of three general phases: inflammatory, proliferative, and remodeling. Each phase involves different cell populations and cytokine levels, creating distinct environments for potential therapeutic intervention. Research has shown that most skin cell types involved in these phases express melanocortin 1 receptor (MC1R), which binds alpha-melanocyte-stimulating hormone (α-MSH). These cells also bind α-MSH analogues such as KPV and KdPT [6].

Alpha-MSH derivatives like KPV retain some of the parent molecule’s properties while lacking others, offering specific benefits in wound healing. For example, KPV maintains α-MSH’s anti-inflammatory effects but does not cause skin pigmentation, making it a suitable candidate for improving wound healing without the pigment changes often linked to natural scar formation, which disproportionately affects individuals with darker skin.

KPV’s anti-inflammatory effects partly result from its role in the innate immune response against common skin pathogens. It has been shown to inhibit the growth of Staphylococcus aureus and Candida albicans at physiological concentrations, suggesting potential to prevent infections in serious wounds such as burns. This combination of anti-inflammatory and antimicrobial activity distinguishes KPV from other anti-inflammatory drugs, which may suppress the body’s infection-fighting ability [8].

Recent research has used KPV as a structural model to develop new therapeutics aiming to replicate its antifungal effects. The three-dimensional structure of KPV appears to be critical to its antifungal properties, and mimicking this structure may allow the creation of compounds with similar activity but different biological effects [9].

Scar Formation

Building on its anti-inflammatory role in the initial phase of wound healing, KPV has also been studied for its effects during the proliferative and remodeling phases. Evidence suggests that KPV can reduce chronic inflammation that contributes to hypertrophic scar formation, such as keloids. These scars are characterized by macrophage infiltration, TNF immunoreactivity, and neutrophil abundance. Administration of α-MSH in such cases results in smaller scars and a reduced inflammatory response [10]. Similar anti-scarring effects have been observed in other tissues, including the lungs and heart, raising the possibility that KPV could help prevent scarring caused by certain chemotherapy agents [11]–[13]. This could reduce side effects from cancer treatments and potentially allow for higher therapeutic doses, improving treatment outcomes.

According to Dr. Didier Merlin, part of KPV’s scar-reducing benefit stems from its ability to modulate collagen metabolism. Both α-MSH and its analogues suppress IL-8 secretion, which in turn inhibits collagen type I production. This mechanism is particularly relevant during the remodeling phase of wound healing. It has also been noted that individuals prone to keloid or hypertrophic scars exhibit lower MC1R mRNA expression in dermal fibroblasts [14].

Source: Wiley Online Library

KPV versus Alpha-MSH

While alpha-MSH is the more potent molecule of the two, it has one serious disadvantage when compared to KPV – it causes skin pigmentation. This side effect alone has been enough to discourage further research into intact alpha-MSH as a potential anti-inflammatory. KPV is favored because it retains most of the anti-inflammatory properties of alpha-MSH yet has none of the side effects. KPV is also exceptionally easy to manufacture and thus has benefit from a cost and logistics standpoint as well[15]. Dr. Thomas Luger, a renowned dermatologist and expert in inflammatory diseases of the skin, has published on KPV extensively. His work demonstrates that the peptide has potent anti-inflammatory properties with few adverse effects.

It is also important to note that the anti-inflammatory effects of KPV appear to be mediated through a different mechanism than those of alpha-MSH. Whereas alpha-MSH binds to specific melanocortin receptors, KPV does not. Evidence of this comes from mouse studies in which blocking MC3/4 receptors, which mediate the anti-inflammatory effects of alpha-MSH, has no impact on the anti-inflammatory effects of KPV. Specifically, blocking these receptors does not block the leukocyte migration effects induced by KPV[16].

Another appealing aspect of KPV is the ease with which the peptide can be administered. Research in animal models has shown that KPV can be administered both orally, subcutaneously and via injection (peripherally or centrally) without serious side effects. Recently, similar research showed that KPV could be administered trans-dermally with success[17]. The ability to administer the drug via multiple routes is not just a matter of convenience either. Different routes of administration affect the way the peptide works and where its anti-inflammatory effects are targeted. The ability to alter the method of delivery makes it possible for scientists to target different areas within the body for treatment.

KPV Summary

KPV is a potent anti-inflammatory peptide that has shown promise in a number of disease conditions. The most active research is in the treatment of inflammatory bowel disease where the peptide has showed substantial promise. KPV has been shown in animal studies to be safe and effective when administered orally, intravenously, subcutaneously and through the skin. Research in wound healing also reveals that KPV and other alpha-MSH derivatives may offer a host of benefits that speed wound healing, reduce infection, fight inflammation, and lead to better cosmetic results. KPV and similar peptides could become mainstays not just in wound healing, but in scar reduction following surgery.

KPV exhibits minimal side effects, low oral and excellent subcutaneous bioavailability in mice. Per kg dosage in mice does not scale to humans. KPV for sale at Peptide Sciences is limited to educational and scientific research only, not for human consumption. Only buy KPV if you are a licensed researcher.

Frequently Asked Questions

Article Author

This literature was researched, edited, and organized by Dr. E. Logan, M.D., who holds a doctorate from Case Western Reserve University School of Medicine and a B.S. in molecular biology.

Scientific Journal Author

Didier Merlin, Ph.D., is a professor at Georgia State University and a research career scientist at the Veterans Affairs Medical Center in Decatur, GA. His work focuses on intestinal epithelia and inflammatory bowel disease. He is a leading researcher on KPV’s development and mechanisms.

Disclaimer: Dr. Merlin does not endorse or advocate the use or sale of KPV products. The citation serves to credit his extensive research.

References

1. M. E. Hiltz and J. M. Lipton, “Antiinflammatory activity of a COOH-terminal fragment of the neuropeptide alpha-MSH,” FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol., vol. 3, no. 11, pp. 2282–2284, Sep. 1989.
2. K. Kannengiesser et al., “Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease,” Inflamm. Bowel Dis., vol. 14, no. 3, pp. 324–331, Mar. 2008, doi: 10.1002/ibd.20334.
3. B. Xiao et al., “Orally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis,” Mol. Ther. J. Am. Soc. Gene Ther., vol. 25, no. 7, pp. 1628–1640, 05 2017, doi: 10.1016/j.ymthe.2016.11.020.
4. G. Dalmasso, L. Charrier-Hisamuddin, H. T. T. Nguyen, Y. Yan, S. Sitaraman, and D. Merlin, “PepT1-Mediated Tripeptide KPV Uptake Reduces Intestinal Inflammation,” Gastroenterology, vol. 134, no. 1, pp. 166–178, Jan. 2008, doi: 10.1053/j.gastro.2007.10.026.
5. D. B. Richards and J. M. Lipton, “Effect of alpha-MSH 11-13 (lysine-proline-valine) on fever in the rabbit,” Peptides, vol. 5, no. 4, pp. 815–817, Aug. 1984, doi: 10.1016/0196-9781(84)90027-5.
6. T. Brzoska, T. A. Luger, C. Maaser, C. Abels, and M. Böhm, “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., vol. 29, no. 5, pp. 581–602, Aug. 2008, doi: 10.1210/er.2007-0027.
7. T. A. Luger and T. Brzoska, “α‐MSH related peptides: a new class of anti‐inflammatory and immunomodulating drugs,” Ann. Rheum. Dis., vol. 66, no. Suppl 3, pp. iii52–iii55, Nov. 2007, doi: 10.1136/ard.2007.079780.
8. M. Cutuli, S. Cristiani, J. M. Lipton, and A. Catania, “Antimicrobial effects of alpha-MSH peptides,” J. Leukoc. Biol., vol. 67, no. 2, pp. 233–239, Feb. 2000, doi: 10.1002/jlb.67.2.233.
9. M. F. Masman et al., “Synthesis and conformational analysis of His-Phe-Arg-Trp-NH2 and analogues with antifungal properties,” Bioorg. Med. Chem., vol. 14, no. 22, pp. 7604–7614, Nov. 2006, doi: 10.1016/j.bmc.2006.07.007.
10. K. S. de Souza et al., “Improved cutaneous wound healing after intraperitoneal injection of alpha-melanocyte-stimulating hormone,” Exp. Dermatol., vol. 24, no. 3, pp. 198–203, Mar. 2015, doi: 10.1111/exd.12609.
11. C. Lonati et al., “Modulatory effects of NDP-MSH in the regenerating liver after partial hepatectomy in rats,” Peptides, vol. 50, pp. 145–152, Dec. 2013, doi: 10.1016/j.peptides.2013.10.014.
12. G. Colombo et al., “Gene expression profiling reveals multiple protective influences of the peptide alpha-melanocyte-stimulating hormone in experimental heart transplantation,” J. Immunol. Baltim. Md 1950, vol. 175, no. 5, pp. 3391–3401, Sep. 2005, doi: 10.4049/jimmunol.175.5.3391.
13. G. Colombo et al., “Production and effects of alpha-melanocyte-stimulating hormone during acute lung injury,” Shock Augusta Ga, vol. 27, no. 3, pp. 326–333, Mar. 2007, doi: 10.1097/01.shk.0000239764.80033.7e.
14. M. Schiller et al., “Human Dermal Fibroblasts Express Prohormone Convertases 1 and 2 and Produce Proopiomelanocortin-Derived Peptides,” J. Invest. Dermatol., vol. 117, no. 2, pp. 227–235, Aug. 2001, doi: 10.1046/j.0022-202x.2001.01412.x.
15. T. Brzoska, M. Böhm, A. Lügering, K. Loser, and T. A. Luger, “Terminal signal: anti-inflammatory effects of α-melanocyte-stimulating hormone related peptides beyond the pharmacophore,” Adv. Exp. Med. Biol., vol. 681, pp. 107–116, 2010, doi: 10.1007/978-1-4419-6354-3_8.
16. S. J. Getting, H. B. Schiöth, and M. Perretti, “Dissection of the anti-inflammatory effect of the core and C-terminal (KPV) alpha-melanocyte-stimulating hormone peptides,” J. Pharmacol. Exp. Ther., vol. 306, no. 2, pp. 631–637, Aug. 2003, doi: 10.1124/jpet.103.051623.
17. K. Pawar, C. S. Kolli, V. K. Rangari, and R. J. Babu, “Transdermal Iontophoretic Delivery of Lysine-Proline-Valine (KPV) Peptide Across Microporated Human Skin,” J. Pharm. Sci., vol. 106, no. 7, pp. 1814–1820, Jul. 2017, doi: 10.1016/j.xphs.2017.03.017.

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