KPV (Lysine-Proline-Valine) [Peptide]

Description

What is KPV?

KPV (Lysine-Proline-Valine; Lys-Pro-Val) is a synthetic tripeptide corresponding to positions 11–13 of alpha-melanocyte-stimulating hormone (α-MSH) specifically the C-terminal three amino acid sequence of this 13-residue melanocortin neuropeptide. α-MSH (sequence Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2) is a cleavage product of pro-opiomelanocortin (POMC) with well-characterised anti-inflammatory, antipyretic, and immunomodulatory activity. KPV is the C-terminal pharmacophore responsible for the anti-inflammatory activity of the parent α-MSH: despite representing only the final three residues of a 13-amino acid peptide, KPV has been shown in preclinical preparations to exert anti-inflammatory activity comparable to or exceeding that of the full-length α-MSH molecule.

KPV was first characterised as an anti-inflammatory active fragment by Hiltz and Lipton in the late 1980s and early 1990s. Subsequent systematic research established that: KPV is the minimum active sequence required for α-MSH anti-inflammatory activity; it acts through intracellular NF-κB pathway inhibition and proinflammatory cytokine suppression; it is transported across intestinal epithelial cell membranes by the di/tripeptide transporter PepT1 — a mechanism that is notably upregulated in inflamed colonic epithelium in inflammatory bowel disease, providing a disease-specific intracellular delivery mechanism; and it reduces lesion severity in two well-validated murine colitis models (DSS and TNBS) in preclinical studies [Kannengiesser et al., 2008].

The commercial research supply of KPV includes both the free tripeptide form (H-Lys-Pro-Val-OH; CAS 67727-97-3; MW 342.440 g/mol) and the terminally modified form (Ac-Lys-Pro-Val-NH2; CAS 112965-21-6; MW 384.48 g/mol). The free tripeptide is the form characterised in the foundational published literature and indexed at PubChem CID 125672. The acetylated/amidated form provides enhanced metabolic stability through dual-terminus exopeptidase protection. Researchers should verify which form is supplied from the product’s analytical documentation. KPV is not approved by the Food and Drug Administration for human or veterinary use. It is not a dietary supplement and is not intended for human consumption or therapeutic self-administration. All RCDbio research compounds are supplied strictly for laboratory and research purposes only.

Chemical Properties

Property	Detail
Product Type	Synthetic Tripeptide / Alpha-MSH C-Terminal Fragment (Melanocortin Anti-Inflammatory Pharmacophore)
Product Name	KPV (Lysine-Proline-Valine)
Application	Scientific / Research Use Only
CAS Number (Free Tripeptide)	67727-97-3 (H-Lys-Pro-Val-OH; free N-terminus, free C-terminus)
CAS Number (Ac-KPV-NH2)	112965-21-6 (Ac-Lys-Pro-Val-NH2; N-acetylated, C-amidated; MW 384.48 g/mol; C17H32N6O4)
Molar Mass	342.440 g/mol (free tripeptide form); 384.48 g/mol (Ac-KPV-NH2 form)
Chemical Formula	C16H30N4O4 (free tripeptide); C17H32N6O4 (Ac-KPV-NH2)
PubChem CID	125672 (free tripeptide H-Lys-Pro-Val-OH)
IUPAC Name	(2S)-2-[[(2S)-1-[(2S)-2,6-diaminohexanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoic acid
Amino Acid Sequence	Lys-Pro-Val; 3 amino acids; corresponds to α-MSH residues 11–13
Parent Compound	α-MSH (Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2; 13 AA; POMC cleavage product)
Synonyms	KPV; Lys-Pro-Val; α-MSH(11-13); MSH(11-13); ACTH(11-13); Melanocortin tripeptide C-terminal
PepT1 Transport	Substrate for human PepT1 (hPepT1; SLC15A1) di/tripeptide transporter; this mechanism is upregulated in IBD colonic epithelium, providing disease-specific intracellular delivery in experimental IBD model systems
Physical Form	Lyophilized white to off-white powder
Solubility	Freely soluble in water; soluble in PBS and standard aqueous buffers
Storage (Lyophilized)	−20°C; sealed container; protected from light and moisture
Storage (Reconstituted)	4°C; use within 48–72 hours; avoid repeated freeze-thaw cycles
Purity	≥98% (HPLC verified, independent third-party laboratory analysis)
WADA Status	KPV is not explicitly named on the 2026 WADA Prohibited List. As a non-approved synthetic melanocortin-derived tripeptide, S0 (Non-Approved Substances) provisions may apply in sport-adjacent research contexts. Verify at GlobalDRO.com before use.

How Does KPV Work?

KPV’s anti-inflammatory activity is mediated through intracellular NF-κB pathway inhibition following cellular entry via PepT1-mediated transport, with additional contributions from direct melanocortin receptor interactions at the cell surface. The intracellular mechanism distinguishes KPV from many conventional anti-inflammatory peptides that act at surface receptors.

PepT1-Mediated Intracellular Transport

PepT1 (hPepT1; SLC15A1) is a proton-coupled di/tripeptide transporter normally expressed in small intestinal enterocytes and upregulated in colonic epithelial cells during intestinal inflammation — a pattern directly relevant to KPV’s research applications in IBD models. KPV is a substrate for PepT1 at physiological concentrations, enabling its transport from the intestinal lumen or extracellular compartment into the cytoplasm of epithelial and immune cells in preclinical preparations. This transport mechanism provides a disease-conditional intracellular delivery pathway: PepT1 upregulation in inflamed colonic epithelium means that more KPV enters inflamed cells than healthy cells, creating a degree of disease-selective intracellular accumulation [Dalmasso et al., 2008]. The intracellular delivery is critical because KPV’s primary mechanism — NF-κB inhibition — requires cytoplasmic access.

NF-κB Pathway Inhibition

Once inside the cell via PepT1 transport, KPV inhibits nuclear factor-kappa B (NF-κB) signalling — the master transcriptional regulator of proinflammatory cytokine expression. In human intestinal epithelial cell preparations (Caco2-BBE, HT29-Cl. 19A) stimulated with proinflammatory cytokines, KPV exposure was associated with reduced NF-κB nuclear translocation, decreased IκBα phosphorylation and degradation, and suppressed downstream proinflammatory gene expression including TNF-α, IL-8, and ICAM-1 [Dalmasso et al., 2008]. This mechanism operates downstream of TNF-α and IL-1β receptor activation, placing KPV at the convergence point of multiple proinflammatory signalling cascades.

Proinflammatory Cytokine Suppression

In macrophage, T cell, and epithelial cell preparations, KPV reduces production of proinflammatory cytokines, including TNF-α, IL-6, IL-8, and nitric oxide under LPS and cytokine stimulation conditions. In T cell preparations, KPV inhibits T cell activation and cytokine production through mechanisms consistent with melanocortin receptor interactions at MC1R and MC3R expressed on immune cells. These surface receptor interactions may complement the intracellular NF-κB inhibition mechanism, though the relative contributions of each pathway have not been fully delineated [Brzoska et al., 2008].

Anti-Inflammatory Activity Relative to Parent α-MSH

Comparative studies in preclinical preparations have established that KPV exerts anti-inflammatory activity comparable to or in some experimental systems exceeding that of full-length α-MSH. This is attributed to KPV’s smaller molecular size, enabling more efficient PepT1-mediated intracellular transport and potentially more favourable pharmacokinetic profiles in biological matrices compared to the 13-residue parent peptide. KPV thus represents the minimum pharmacophore required for α-MSH anti-inflammatory activity — a finding with implications for both basic melanocortin system research and anti-inflammatory peptide design [Brzoska et al., 2008].

Key Research Findings

In preclinical and in vitro research contexts, KPV has been associated with the following observations:

• IBD mouse model activity: KPV reduced lesion severity in both DSS-induced and TNBS-induced colitis murine models; effects observed via reduced macroscopic and histological inflammation scores [Kannengiesser et al., 2008].
• PepT1-mediated intracellular delivery: KPV is confirmed as a PepT1 substrate; intracellular delivery and NF-κB inhibition in Caco2-BBE and HT29-Cl. 19A cells characterised; transport upregulated in IBD epithelium, creating disease-selective delivery [Dalmasso et al., 2008].
• Stronger than parent α-MSH: KPV exerts anti-inflammatory activity comparable to or exceeding full-length α-MSH in matched preclinical cell and model preparations — the minimum active fragment exhibiting the full anti-inflammatory pharmacophore [Brzoska et al., 2008].
• NF-κB inhibition: Reduced IκBα phosphorylation, NF-κB nuclear translocation, and downstream proinflammatory gene expression in human intestinal epithelial and immune cell preparations following KPV exposure.
• Broader melanocortin anti-inflammatory context: KPV is one of a family of melanocortin-derived tripeptides with anti-inflammatory activity; structurally related compound KdPT (Lys-D-Pro-Thr; corresponding to IL-1β residues 193–195) shows similar IBD model efficacy; both are investigated alongside KPV in comparative melanocortin fragment pharmacology [Brzoska et al., 2010].

All findings listed above are derived from preclinical in vitro and in vivo data. No regulatory-grade human clinical trial data have been established for KPV. These observations do not constitute evidence of efficacy or safety in any human condition or organism.

What are the Potential Research Applications of KPV?

In controlled laboratory environments, KPV has been investigated for the following research applications. These do not constitute claims of efficacy or safety in any organism.

NF-κB Anti-Inflammatory Pathway Research KPV is employed as a melanocortin-derived NF-κB inhibitor reference compound in studies characterising IκBα/NF-κB signalling cascade inhibition, proinflammatory cytokine suppression, and downstream gene expression changes in intestinal epithelial cells, macrophages, T cells, and dendritic cells. Research examines the intracellular pathway through which KPV inhibits NF-κB activation downstream of multiple proinflammatory receptor systems.

PepT1 Di/Tripeptide Transporter Biology KPV is employed as a model PepT1 substrate in studies characterising hPepT1 transport kinetics, substrate specificity, and disease-conditioned expression changes in intestinal epithelial cell systems. Research examines how PepT1 upregulation in inflamed colonic epithelium creates preferential intracellular delivery of KPV in inflammatory versus healthy tissue models.

Inflammatory Bowel Disease Preclinical Research In DSS-induced and TNBS-induced colitis rodent models, KPV is investigated for effects on macroscopic disease activity indices, histological inflammation scores, cytokine profiles, and epithelial barrier integrity. Research examines whether PepT1-mediated intracellular delivery enables disease-selective anti-inflammatory activity in matched inflamed versus healthy colon tissue preparations.

Melanocortin System and α-MSH Fragment Pharmacology KPV is employed as the primary anti-inflammatory pharmacophore reference compound in comparative melanocortin fragment studies alongside full-length α-MSH, KdPT, and other melanocortin-derived tripeptides. Research characterises structure-activity relationships within the melanocortin tripeptide series, examining how conservative amino acid substitutions (Lys→D-Lys, Pro→D-Pro, Val→Thr) alter anti-inflammatory potency, receptor selectivity, and transport properties.

Nanoparticle Drug Delivery and Targeted Intestinal Research KPV has been employed as the active cargo in functionalized nanoparticle (NP) delivery systems — including hyaluronic acid-functionalized NPs — for targeted delivery to colonic epithelial cells and macrophages in experimental UC model systems. Research characterises NP-KPV formulation characteristics, cellular uptake mechanisms, and comparative anti-inflammatory efficacy versus free KPV in matched systems.

What are the Potential Side Effects of KPV?

The following observations are from preclinical research.

• Generally well-tolerated profile in in vitro and in vivo preclinical systems at research-relevant concentrations; no significant acute toxicity reported in published murine colitis model studies at effective doses
• KPV lacks the melanin-stimulating activity of full-length α-MSH (which contains the His-Phe-Arg-Trp pharmacophore for MC1R pigmentation signalling at positions 6–9); no pigmentation-related effects expected in preclinical model systems
• As a substrate for PepT1, KPV may compete with endogenous di/tripeptides and physiological PepT1 substrates at enterocyte transporters in high-concentration in vitro assay systems — a relevant experimental design consideration
• No human safety or tolerability data have been established for KPV. These observations are derived from preclinical experimental systems and should not be extrapolated to human or animal outcomes.

Risk & Handling

Handling Precautions

KPV should only be handled by trained laboratory personnel. Appropriate PPE is required: nitrile gloves, a laboratory coat, and eye protection. When working with lyophilized powder, use within a laminar flow cabinet. Avoid aerosol generation during reconstitution.

Exposure Risks

Risk Tier: LOW

KPV has demonstrated a well-tolerated profile in published preclinical cell culture and rodent in vivo studies. As a small, water-soluble tripeptide, KPV is expected to be rapidly cleared from systemic circulation in the event of accidental exposure. Its anti-inflammatory, NF-κB-inhibitory pharmacological activity means that systemic exposure may produce anti-inflammatory effects in tissues expressing PepT1 and MC receptors. No human safety or tolerability data have been established for KPV.

Storage

• Lyophilized form: Store at −20°C in original sealed, light-protected container with desiccant
• Reconstituted form: Store at 4°C; use within 48–72 hours of reconstitution
• Do not subject to repeated freeze-thaw cycles; tripeptide integrity may be compromised
• Protect from prolonged light exposure and moisture

Frequently Asked Questions

Q: What is KPV, and what is it investigated for in research? A: KPV (Lys-Pro-Val; CAS 67727-97-3) is a synthetic tripeptide corresponding to the C-terminal residues 11–13 of alpha-MSH. It is the minimum active fragment responsible for α-MSH’s anti-inflammatory activity and is investigated in preclinical research contexts for NF-κB pathway inhibition, PepT1-mediated intracellular transport biology, murine IBD model anti-inflammatory effects, and comparative melanocortin fragment pharmacology. It is not approved by the FDA and is intended strictly for laboratory research purposes.

Q: How is KPV different from full-length α-MSH? A: Alpha-MSH (13 AA) contains the His-Phe-Arg-Trp pharmacophore at positions 6–9 responsible for its melanin-stimulating (MC1R) and additional melanocortin receptor activities, alongside the Lys-Pro-Val C-terminal anti-inflammatory pharmacophore. KPV (3 AA) retains only the anti-inflammatory pharmacophore, lacking the melanin-stimulating activity entirely. In comparative preclinical preparations, KPV exerts anti-inflammatory activity comparable to or exceeding full-length α-MSH — suggesting the C-terminal tripeptide is both necessary and sufficient for α-MSH’s anti-inflammatory effects without the confounding melanocortin receptor signalling from the rest of the sequence.

Q: What is the free tripeptide (CAS 67727-97-3) versus the Ac-KPV-NH2 form (CAS 112965-21-6)? A: The free tripeptide (H-Lys-Pro-Val-OH; CAS 67727-97-3; MW 342.440 g/mol) is the form indexed in PubChem CID 125672 and used in the foundational published literature. The Ac-KPV-NH2 form (CAS 112965-21-6; MW 384.48 g/mol) carries N-terminal acetylation and C-terminal amidation for enhanced metabolic stability. Both forms retain the Lys-Pro-Val core sequence. Researchers should verify from the product COA which form is supplied and account for terminal modification differences when comparing with published literature data.

Q: What is the role of PepT1 in KPV research? A: PepT1 is a proton-coupled di/tripeptide transporter (SLC15A1) normally expressed in small intestinal epithelium and upregulated in colonic epithelium during inflammation. KPV is a PepT1 substrate, enabling its active transport into intestinal epithelial cells and immune cells. The upregulation of colonic PepT1 in IBD creates preferential intracellular accumulation of KPV in inflamed versus healthy tissue, providing a disease-conditional delivery mechanism. Once inside the cell, KPV inhibits NF-κB signalling — its primary anti-inflammatory mechanism requires intracellular access, making PepT1-mediated transport central to understanding KPV’s mechanism in IBD research models [Dalmasso et al., 2008].

Q: How should KPV be stored? A: Lyophilized KPV should be stored at −20°C in a sealed, light-protected container with desiccant. Once reconstituted, store at 4°C and use within 48–72 hours. Repeated freeze-thaw cycles are not recommended.

Q: What toxicity observations have been reported for KPV in preclinical studies? A: KPV has demonstrated a well-tolerated profile in published in vitro cell culture and murine colitis model studies at effective anti-inflammatory doses. No significant acute toxicity has been reported in published preclinical literature at research-relevant concentrations. No human safety or tolerability data have been established. These observations should not be extrapolated to human or animal outcomes.

Related Research Compounds

Researchers investigating KPV may also be interested in the following compounds currently available for laboratory research at RCDbio:

• Selank — A synthetic tuftsin-derived heptapeptide investigated for immune pathway modulation and GABAergic research; shares the neuropeptide-derived immunomodulatory research context with KPV’s melanocortin anti-inflammatory pathway studies.
• VIP (Vasoactive Intestinal Peptide) — A 28-amino acid neuropeptide investigated for VPAC1/VPAC2-mediated immunomodulation and anti-inflammatory pathway research; shares the neuropeptide immunomodulation context with KPV’s α-MSH-derived anti-inflammatory mechanism studies.

All products listed are for laboratory and research purposes only.

References

1. Kannengiesser, K., Maaser, C., Heidemann, J., Luegering, A., Ross, M., Brzoska, T., Bohm, M., Luger, T. A., Domschke, W., & Kucharzik, T. (2008). Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease. Inflammatory Bowel Diseases, 14(3), 324–331. https://pubmed.ncbi.nlm.nih.gov/18092346/

2. Dalmasso, G., Charrier-Hisamuddin, L., Nguyen, H. T. T., Yan, Y., Sitaraman, S., & Merlin, D. (2008). PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation. Gastroenterology, 134(1), 166–178. https://pubmed.ncbi.nlm.nih.gov/18061177/

3. Brzoska, T., Luger, T. A., Maaser, C., Abels, C., & Böhm, M. (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. https://pubmed.ncbi.nlm.nih.gov/18612139/

4. Brzoska, T., Böhm, M., Lügering, A., Loser, K., & Luger, T. A. (2010). Terminal signal: anti-inflammatory effects of α-melanocyte-stimulating hormone-related peptides beyond the pharmacophore. Advances in Experimental Medicine and Biology, 681, 107–116. https://pubmed.ncbi.nlm.nih.gov/21222263/ 

Disclaimer

KPV (Lysine-Proline-Valine) is exclusively for laboratory research purposes. RCDbio products are not intended to diagnose, prevent, treat, or cure any disease or medical condition.

The Food and Drug Administration has not evaluated the statements on our website. This product is not approved for human or veterinary use. Researchers must comply with all applicable local, state, and federal laws and regulations governing the purchase and use of research compounds. By purchasing, you agree to our Terms and Conditions. RCDbio reserves the right to refuse sales to unauthorized individuals.

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