KPV

Overview

KPV is a synthetic tripeptide corresponding to amino acids 11-13 of α-melanocyte-stimulating hormone (α-MSH). It is the smallest fragment of α-MSH to which consistent anti-inflammatory activity has been attributed. Its compactness (only three amino acids) makes it scientifically interesting as a minimal biologically active unit of a larger hormone.

α-MSH is an evolutionarily ancient neuropeptide with a role in regulating inflammatory responses. KPV shares part of the anti-inflammatory properties of the parent molecule, but acts via a mechanism that is partly independent of the classical melanocortin receptors. Where intact α-MSH signals via the MC-1 receptor and cAMP, KPV inhibits NF-κB translocation via a cAMP-independent pathway, a distinction relevant to understanding melanocortin signalling.

The most studied effect of KPV is inhibition of NF-κB, a central transcription factor driving inflammatory responses. Across several cell models (macrophages, keratinocytes, and alveolar epithelium), KPV (or closely related analogues) showed dose-dependent inhibition of NF-κB activation and reduction of pro-inflammatory markers such as NO, TNF-α, and IL-1β.

In vitro, KPV also showed antimicrobial properties against Staphylococcus aureus and Candida albicans, and neuroprotective effects after traumatic brain injury in an animal model. The evidence base is predominantly in vitro and early preclinical. Controlled human studies are entirely absent.

Mechanism of action

KPV inhibits NF-κB translocation via a cAMP-independent mechanism, reduces pro-inflammatory cytokine and NO production, and shows direct antimicrobial activity in vitro.

NF-κB inhibition

• Dose-dependently inhibits nuclear translocation of the NF-κB subunits p50, p65, and p75
• Acts via a cAMP-independent pathway, distinct from intact α-MSH
• Stabilises IκB-α in the cytosol, restraining NF-κB migration to the nucleus
• In alveolar epithelium this was shown with the analogue KP-D-Val (KPDV), partly via IL-1 receptor antagonism

Reduction of pro-inflammatory markers

• Reduces NO production in macrophages after LPS/IFN-γ stimulation (mouse macrophage cell line RAW 264.7)
• Comparable order of potency to intact α-MSH in NO inhibition
• Associated with reduced TNF-α and IL-1β expression

Antimicrobial activity (in vitro)

• Inhibits colony formation of Staphylococcus aureus
• Reduces viability and germ-tube formation of Candida albicans
• Increases cellular cAMP in pathogens, a proposed mechanism for the antimicrobial effect

Research findings

• KPV inhibits NF-κB translocation in macrophages with comparable maximal potency to intact α-MSH, but via a cAMP-independent mechanism (RAW 264.7 cells)
• In human keratinocytes, KPV did not raise cAMP; an acute intracellular calcium signal occurred, but only in the presence of the adenosine agonist PIA. MC-1 receptor binding of the KPV peptides was demonstrated in transfected CHO cells
• In vitro, KPV showed antimicrobial activity against both S. aureus and C. albicans
• Single administration of KPV after traumatic brain injury reduced secondary lesion size, microglial activation, and neuronal apoptosis in a mouse model
• In alveolar epithelium, the analogue KP-D-Val (KPDV) blocked LPS-induced NF-κB activation, partly via IL-1 receptor antagonism

In vitro findings

• Inhibition of NF-κB translocation in macrophages, keratinocytes, and alveolar epithelium (partly with the KPDV analogue)
• Reduction of NO, TNF-α, and IL-1β production after LPS stimulation
• Antimicrobial activity against S. aureus and C. albicans
• Signalling in human keratinocytes: KPV did not raise cAMP; an acute calcium signal occurred only in the presence of the adenosine agonist PIA. MC-1 receptor binding was demonstrated in transfected CHO cells

Animal model findings

• Reduced secondary injury size after traumatic brain injury in mice following single administration
• Reduced microglial activation and neuronal apoptosis after brain trauma
• Neuroprotective effect via modulation of inflammatory and apoptotic pathways

Human data

• There are no controlled human intervention studies
• In-vitro data in human cell lines (keratinocytes, alveolar epithelium) are available
• Clinical translation is unknown

Research context

KPV is scientifically interesting as a minimal biologically active unit of α-MSH. The fact that three amino acids suffice for anti-inflammatory activity of the same order as the full hormone offers insight into the structure-activity relationship of melanocortin signalling. This also makes KPV a useful pharmacological probe for research into NF-κB modulation.

The consistency of the NF-κB inhibition data across several cell types (macrophages, keratinocytes, alveolar epithelium) is a positive signal for the reproducibility of the mechanism. One nuance accompanies this: part of this work was carried out with closely related analogues (such as KP-D-Val) and in cell lines of varied origin, including mouse and hamster cells.

The translational step to humans is entirely unmade. There are no human pharmacokinetic data, no in-vivo toxicological studies, and no clinical trials. The evidence base is mechanistically interesting but lies entirely in the early research phase.

Open questions

KPV has a scientifically interesting mechanistic profile that is consistent across several cell models. The distance to clinical applicability in humans is, however, large. All essential translational steps are still missing.

• There are no in-vivo pharmacokinetic data; biodistribution, half-life, and metabolism in humans are unknown
• There are no human intervention studies of any kind
• The optimal route of administration for systemic versus local effects has not been studied
• The long-term safety profile is unknown
• The relevance of the in-vitro NF-κB inhibition data to in-vivo inflammation models has not been demonstrated
• Part of the mechanistic evidence rests on analogues (KPDV); the extent to which this applies one-to-one to pure KPV has not been fully established
• The interaction with the endogenous α-MSH system under chronic use is unknown

Research outlook

In-vivo studies in inflammation models are the logical next step after the in-vitro basis

Intestinal inflammation (colitis) and skin inflammation are the most studied indication areas in the related α-MSH literature

Nanoparticle and controlled-release formulations are being explored for local administration

Comparative work between pure KPV and its analogues (such as KPDV) could sharpen the mechanism

Scientific interest

NF-κB modulation via melanocortin signalling

Minimal biologically active fragments of neuropeptides

Antimicrobial peptides and innate immunity

Neuroprotection in neuroinflammation

Specifications

References

1. Antimicrobial effects of alpha-MSH peptides. · Cutuli M, Cristiani S, Lipton JM, Catania A. · Journal of Leukocyte Biology · 2000
2. The neuroimmunomodulatory peptide alpha-MSH. · Ichiyama T, Sato S, Okada K, Catania A, Lipton JM. · Annals of the New York Academy of Sciences · 2000
3. Alpha-melanocyte-related tripeptide, Lys-d-Pro-Val, ameliorates endotoxin-induced nuclear factor kappaB translocation and activation. · Haddad JJ, Lauterbach R, Saadé NE, et al. · Biochemical Journal · 2001
4. Effects of melanocortin peptides on lipopolysaccharide/interferon-gamma-induced NF-kappaB DNA binding and nitric oxide production in macrophage-like RAW 264.7 cells. · Mandrika I, Muceniece R, Wikberg JE. · Biochemical Pharmacology · 2001
5. alpha-Melanocyte-stimulating hormone, MSH 11-13 KPV and adrenocorticotropic hormone signalling in human keratinocyte cells. · Elliott RJ, Szabo M, Wagner MJ, et al. · Journal of Investigative Dermatology · 2004
6. Single administration of tripeptide alpha-MSH(11-13) attenuates brain damage by reduced inflammation and apoptosis after experimental traumatic brain injury in mice. · Schaible EV, Steinsträsser A, Jahn-Eimermacher A, et al. · PLoS One · 2013

Availability

In stock · Batch PEP-KPV-2026-01 · HPLC 99.13 % · released 21 Jun 2026

• KPV 5 mg · product page with price and batch CoA