KPV (Lysine-Proline-Valine) [Nasal Spray]

Description

What is KPV Nasal Spray?

KPV is a synthetic tripeptide corresponding to positions 11-13 of alpha-melanocyte-stimulating hormone (alpha-MSH), the 13-amino acid neuropeptide produced by post-translational processing of proopiomelanocortin (POMC) in the pituitary gland and peripheral tissues. Alpha-MSH has the primary sequence Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val, with KPV occupying the C-terminal three residues at positions 11, 12, and 13. The tripeptide is joined by standard alpha-peptide bonds in the sequence Lys(11)-Pro(12)-Val(13) and is supplied as the free acid form (C-terminal carboxyl group unmodified). KPV was identified as the minimal structural unit of alpha-MSH responsible for the parent peptide’s anti-inflammatory and antipyretic activities, a finding that has been established across multiple independent research groups and model systems since the early 1990s. Because KPV lacks the melanotropic pharmacophore (the His-Phe-Arg-Trp core sequence at positions 6-9 of alpha-MSH required for melanocortin receptor binding and pigmentation effects), it does not produce the pigmentation or melanotropic effects associated with the full-length alpha-MSH sequence, while retaining the anti-inflammatory activity of the parent peptide [Luger & Brzoska, 2007; PMID 17934097].

KPV is distinct from full-length alpha-MSH (13 AA; MW approximately 1665 g/mol; CAS 581-05-5) in molecular weight, structural complexity, receptor binding profile, and pharmacological activity range. KPV is also distinct from a structurally related derivative, KdPT (also written K(D)PT; lysine-D-proline-threonine), which has been proposed to correspond to residues 193-195 of interleukin-1 beta (IL-1beta) and has been characterized as capable of interacting with the IL-1 receptor type I in addition to melanocortin receptors. KPV and KdPT are researched as complementary anti-inflammatory tripeptides with overlapping but mechanistically distinct activity profiles. The research-grade KPV nasal spray supplied by RCDbio supplies H-Lys-Pro-Val-OH only and is not equivalent to KdPT or to any alpha-MSH analog with additional modifications.

KPV has not been approved by the Food and Drug Administration for any human therapeutic indication via the intranasal route or any other route. KPV was classified as a 503A Category 2 bulk drug substance in late 2023, placing it under the most restrictive FDA compounding classification, which prohibits its compounding under Section 503A under any circumstances. KPV was removed from Category 2 effective April 15, 2026. It is scheduled for Pharmacy Compounding Advisory Committee (PCAC) evaluation on July 23, 2026, under Docket No. FDA-2026-N-2979. Removal from Category 2 does not authorize compounding; KPV remains unavailable for legitimate compounding until after the PCAC review and any subsequent FDA rulemaking. The research-grade nasal spray formulation supplied by RCDbio is not a pharmaceutical product and is not equivalent to any compounded or pharmaceutical formulation.

The nasal spray formulation is investigated as a delivery route in preclinical research contexts, based on evidence of olfactory bulb-mediated CNS transport for peptide compounds administered intranasally in rodent models. The nasal mucosa’s proximity to the central nervous system via the olfactory nerve makes it a research-relevant delivery route for CNS-active anti-inflammatory research compounds. Alpha-MSH is endogenously produced in the brain and modulates CNS inflammatory responses via melanocortin receptors expressed on central neurons and glial cells; intranasal delivery of the KPV fragment is investigated as an approach to access these CNS anti-inflammatory targets [Wong et al., 2024; PMID 38441832].

DISCLAIMER: KPV (Lysine-Proline-Valine) Nasal Spray as supplied by RCDbio is not a dietary supplement and has not been approved by the Food and Drug Administration for human use, veterinary use, consumption, or any therapeutic application. This product is not intended for human consumption or therapeutic self-administration. It is supplied exclusively for in vitro and preclinical laboratory research purposes. All RCDbio research compounds are for laboratory and research purposes only.

Chemical Properties of KPV

Property	Details
Product Type	Synthetic Melanocortin-Derived Tripeptide / C-Terminal alpha-MSH Fragment (Positions 11-13) / NF-kB Inhibitor / Anti-Inflammatory Research Peptide / Melanocortin Pathway Modulator
Product Name	KPV (Lysine-Proline-Valine) Nasal Spray
Application	Scientific / Research Use Only
CAS Number	67727-97-3 (H-Lys-Pro-Val-OH; KPV free acid)
Molar Mass	342.44 g/mol
Chemical Formula	C16H30N4O4
IUPAC Name	(2S)-2-[[(2S)-1-[(2S)-2,6-diaminohexanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoic acid (PubChem CID 125672)
Synonyms	KPV; Lys-Pro-Val; H-Lys-Pro-Val-OH; alpha-MSH(11-13); alpha-MSH C-terminal tripeptide; ACTH(11-13); MSH 11-13; Lysine-Proline-Valine; KPV free acid. Note: KPV is distinct from KdPT (K(D)PT; Lys-D-Pro-Thr)
Physical Form	Lyophilized white to off-white powder (compound); supplied as aqueous nasal spray solution
Solubility	Freely soluble in water at >=1 mg/mL; soluble in sterile saline. KPV is highly hydrophilic due to the lysine epsilon-amino group and the valine carboxylate terminus
Storage (Lyophilized)	-20°C; sealed container; protected from light and moisture
Storage (Reconstituted / Nasal Spray)	2-8°C; use within 28 days of first actuation; DO NOT FREEZE; protect from light; keep upright
PubChem CID	125672 (H-Lys-Pro-Val-OH; KPV free acid
Purity	>=98% (HPLC verified, independent third-party laboratory analysis; COA available per batch)
WADA Status	KPV is not explicitly named on the 2026 WADA Prohibited List. As a melanocortin-derived anti-inflammatory tripeptide, not a growth factor, peptide hormone, or performance-enhancing substance within currently named prohibited categories,  it does not fall within explicitly prohibited substance classes at this time. Researchers operating within WADA Code contexts should verify current status at GlobalDRO.com prior to any use. RCDbio products are for laboratory research purposes only.

How Does KPV Work?

KPV exerts its anti-inflammatory activity through two mechanistically distinct but complementary pathways: (1) receptor-mediated signaling at melanocortin receptors (MCRs), primarily MC1R and MC3R; and (2) receptor-independent intracellular mechanisms, most notably direct inhibition of NF-kB nuclear translocation. The second pathway is of particular research significance because it operates independently of MCR binding — KPV produces anti-inflammatory effects in MC1R-nonfunctional (MC1Re/e) mice, demonstrating that melanocortin receptor engagement is not required for its full anti-inflammatory activity [Kannengiesser et al., 2008; PMID 18092346]. The following mechanistic observations are from in vitro and preclinical data only.

NF-kB Inhibition — The Primary Anti-Inflammatory Mechanism

The principal intracellular anti-inflammatory mechanism of KPV is inhibition of NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells) activation. NF-kB is the master transcription factor regulating the expression of pro-inflammatory cytokines (TNF-alpha, IL-1beta, IL-6, IL-8), adhesion molecules (ICAM-1, VCAM-1), chemokine receptors, and other inflammatory mediators. Under normal conditions, NF-kB is retained in the cytoplasm by binding to its inhibitory protein IkB-alpha. Pro-inflammatory stimuli (LPS, TNF-alpha, IL-1beta) activate IKK, which phosphorylates IkB-alpha, targeting it for proteasomal degradation and releasing NF-kB to translocate to the nucleus. KPV and the parent alpha-MSH peptide inhibit NF-kB activation through preservation of IkB-alpha — preventing its phosphorylation and proteasomal degradation, thereby blocking NF-kB nuclear import and downstream pro-inflammatory gene transcription [Ichiyama et al., 2000; PMID 11268347]. This mechanism operates in peripheral immune cells, intestinal epithelial cells, and central nervous system glia, giving KPV a broad anti-inflammatory research profile across tissue compartments.

Melanocortin Receptor Modulation (MC1R and MC3R)

Alpha-MSH exerts anti-inflammatory effects via melanocortin receptors expressed on immune cells (MC1R on macrophages, dendritic cells, T cells), intestinal epithelial cells (MC3R), and CNS neurons and astrocytes (MC3R, MC4R). KPV, as the C-terminal tripeptide of alpha-MSH, retains partial MCR modulatory activity — binding capacity studies indicate it can interact with MC1R and MC3R, though with lower affinity than full-length alpha-MSH. Crucially, studies in MC1R-nonfunctional mice (MC1Re/e) demonstrate that KPV retains significant anti-inflammatory activity even when MC1R signaling is abolished, confirming that NF-kB inhibition and other receptor-independent pathways account for a substantial component of KPV’s activity [Kannengiesser et al., 2008; PMID 18092346]. MC3R is expressed on intestinal epithelial cells and airway epithelium; KPV-mediated activation of MC3R is proposed as a mechanism for its anti-inflammatory effects in gut and airway epithelial model preparations.

Pro-inflammatory Cytokine Suppression

KPV suppresses the production and action of multiple pro-inflammatory cytokines through its NF-kB inhibitory and MCR modulatory mechanisms. Documented cytokine effects in preclinical model systems include inhibition of IL-1beta production and signaling (a primary proposed target for KPV’s anti-inflammatory activity), suppression of TNF-alpha, IL-6, and IL-8 production in macrophage and dendritic cell preparations, and inhibition of adhesion molecule expression (ICAM-1, VCAM-1) that reduces inflammatory cell recruitment to inflamed tissue sites [Luger & Brzoska, 2007; PMID 17934097]. These cytokine suppression effects are documented in cell and animal model systems and have not been established in human clinical trials.

Anti-inflammatory Activity Independent of Melanotropic Effects

A pharmacologically significant property of KPV relative to full-length alpha-MSH is its lack of melanotropic activity. The melanotropic pharmacophore of alpha-MSH — the His-Phe-Arg-Trp sequence at positions 6-9 — is required for melanocortin receptor-mediated pigmentation (melanogenesis stimulation). KPV lacks this pharmacophore entirely. As a result, KPV does not stimulate melanin production in melanocyte preparations and does not produce the pigmentation-related effects of full-length alpha-MSH or synthetic melanocortin receptor agonists such as Melanotan-I or Melanotan-II. This selective absence of melanotropic activity while retaining anti-inflammatory activity makes KPV a pharmacologically cleaner research tool for investigating melanocortin-pathway anti-inflammatory signaling without melanogenesis confounds.

Preclinical Intestinal Anti-inflammatory Activity

In two independent murine colitis model preparations, DSS (dextran sodium sulfate)-induced colitis and CD45RBhi T-cell transfer colitis, KPV treatment produced significantly stronger body weight recovery, histologically confirmed reduction of inflammatory infiltrates in colonic tissue, and significant reduction of myeloperoxidase (MPO) activity in colonic tissue compared to vehicle controls. In the DSS model, KPV treatment rescued all animals in the MC1Re/e treatment group from death during colitis induction, demonstrating anti-inflammatory activity via MC1R-independent pathways [Kannengiesser et al., 2008; PMID 18092346]. These are preclinical mouse model data; they do not constitute evidence of efficacy for the research-grade nasal spray formulation in any organism.

Intranasal Delivery & Pharmacokinetics

Olfactory Bulb-Mediated CNS Transport

When administered intranasally in preclinical rodent model systems, peptide compounds can access the central nervous system through the olfactory nerve (cranial nerve I) pathway. Compounds deposited on the olfactory mucosa are transported along olfactory axons through the cribriform plate to the olfactory bulb, from which access to deeper CNS structures,  including the hypothalamus, brainstem, and cortex, where melanocortin receptors are expressed, has been characterized in rodent preparations. The olfactory and trigeminal nerve pathways for nose-to-brain peptide transport have been investigated in preclinical studies of peptide delivery [Wong et al., 2024; PMID 38441832]. Alpha-MSH is endogenously produced in the hypothalamus and acts on CNS melanocortin receptors to modulate neuroinflammation and descending anti-inflammatory neural pathways; intranasal delivery of the KPV fragment is a research-relevant approach to accessing these targets. No compound-specific intranasal pharmacokinetic or CNS delivery data has been published for KPV as of June 2026.

Nasal Mucosal Stability

KPV (H-Lys-Pro-Val-OH) is a small tripeptide (MW 342.44 g/mol; approximately 0.34 kDa) with no N-terminal acetylation. The nasal mucosa expresses aminopeptidases that cleave free N-terminal amino groups; KPV’s free N-terminal lysine is therefore susceptible to aminopeptidase-mediated degradation at the nasal mucosa, unlike the N-terminally acetylated TB-500 (Ac-LKKTETQ) in this range. Proline at position 2 (Pro-12 of alpha-MSH) provides partial resistance to sequential aminopeptidase activity because the imino nitrogen of proline creates a steric barrier to certain aminopeptidases; this partial resistance is a known structural feature of proline-containing tripeptides. No formal nasal mucosal stability data for KPV has been published.

Nasal Mucosal Absorption

At 342.44 g/mol (~0.34 kDa), KPV is among the smallest molecular weight compounds in the RCDbio nasal spray research range. This small size is favorable for paracellular absorption across the nasal mucosa. However, KPV is highly hydrophilic due to the lysine epsilon-amino group (positively charged at physiological pH) and the free C-terminal carboxylate, which together limit passive transcellular diffusion across lipid bilayers. Paracellular and transporter-mediated mechanisms are the expected primary absorption pathways. No specific nasal mucosal permeability data for KPV has been published.

Compound-Specific Pharmacokinetics

No formal intranasal pharmacokinetic parameters (Tmax, Cmax, CNS bioavailability) have been published for KPV as of June 2026. KPV is susceptible to protease degradation in biological fluids, with the proline at position 2 providing partial aminopeptidase resistance. Published pharmacokinetic data for alpha-MSH administered via other routes cannot be directly extrapolated to the KPV tripeptide via intranasal delivery. Researchers should account for the absence of published intranasal pharmacokinetic data when designing laboratory protocols.

Key Research Findings

The Neuroimmunomodulatory Peptide alpha-MSH — NF-kB Inhibition and KPV Anti-inflammatory Activity (Review, Ann N Y Acad Sci, 2000): Alpha-MSH modulates the production and action of pro-inflammatory cytokines in inflammatory cells, peripheral tissues, and the central nervous system via endogenous melanocortin receptors; the key to the anti-inflammatory influence is inhibition of NF-kB through preservation of IkB-alpha, preventing NF-kB nuclear migration; alpha-MSH and its C-terminal fragment KPV modulate inflammation via direct peripheral actions, CNS anti-inflammatory pathway modulation, and descending neural anti-inflammatory pathways controlling peripheral inflammation [Ichiyama et al., 2000; PMID 11268347]

alpha-MSH Related Peptides as Anti-inflammatory and Immunomodulating Drugs (Review, Ann Rheum Dis, 2007): alpha-MSH has potent anti-inflammatory effects mediated by direct effects on immune system cells and indirect effects on resident non-immune cells; alpha-MSH affects NF-kB activation, adhesion molecule expression, chemokine receptor expression, pro-inflammatory cytokine production, and inflammatory cell migration; most anti-inflammatory activities of alpha-MSH can be attributed to its C-terminal tripeptide KPV; KPV and the related tripeptide KdPT have favorable physicochemical properties for development as anti-inflammatory agents for skin, eye, bowel, and airway inflammatory disease [Luger & Brzoska, 2007; PMID 17934097]

KPV Shows Anti-inflammatory Potential in Murine Models of Inflammatory Bowel Disease (Preclinical, Inflamm Bowel Dis, 2008): In DSS-colitis mouse model, KPV treatment produced earlier recovery and significantly stronger body weight regain versus vehicle; histological inflammatory infiltrates significantly reduced; myeloperoxidase activity significantly reduced in colonic tissue; in CD45RBhi transfer colitis model, KPV treatment produced recovery, body weight regain, and reduced histological inflammatory changes; in MC1R-nonfunctional mice (MC1Re/e), KPV treatment rescued all animals in the treatment group from death during DSS colitis, demonstrating anti-inflammatory activity at least partially independent of MC1R signaling [Kannengiesser et al., 2008; PMID 18092346]

Row 1 characterizes the NF-kB inhibitory mechanism of alpha-MSH and its KPV fragment, establishing the mechanistic basis for KPV’s anti-inflammatory research activity in peripheral and CNS model systems. Row 2 is a class-level review establishing KPV as the principal anti-inflammatory pharmacophore of alpha-MSH and summarizing preclinical evidence across multiple inflammatory disease models. Row 3 is the primary KPV-specific preclinical study, providing direct evidence of anti-inflammatory activity in two independent IBD mouse model preparations and establishing partial MC1R independence. No human clinical trials for KPV administered via any route have been published as of June 2026. No published peer-reviewed study has characterized intranasal delivery of KPV specifically. These observations do not constitute evidence of efficacy or safety for the research-grade nasal spray formulation in any organism.

What are the Potential Research Applications?

In controlled laboratory environments, KPV nasal spray has been investigated for the following research applications. These are observed in preclinical and in vitro contexts only and do not constitute claims of efficacy or safety in any organism.

NF-kB Signaling and Anti-Inflammatory Pathway Research

KPV is a research tool for investigating NF-kB-dependent anti-inflammatory signaling at defined concentrations without the melanotropic confounds of full-length alpha-MSH. Research applications include IkB-alpha phosphorylation and degradation assays in LPS-stimulated macrophage and dendritic cell preparations, NF-kB p65 nuclear translocation inhibition studies, pro-inflammatory cytokine (TNF-alpha, IL-1beta, IL-6) suppression assays, ICAM-1 and VCAM-1 adhesion molecule expression studies in endothelial cell preparations, and comparative NF-kB inhibition studies contrasting KPV versus full-length alpha-MSH versus KdPT in matched cell preparations.

Melanocortin Receptor Pharmacology Research

KPV retains partial MCR binding activity while lacking the melanotropic pharmacophore, making it a research tool for isolating anti-inflammatory MCR signaling from melanogenic effects. Research applications include MC1R and MC3R binding studies comparing KPV versus alpha-MSH and synthetic MCR agonists, cAMP pathway activation assays downstream of MCR engagement, comparison of KPV anti-inflammatory activity in MC1R-expressing versus MC1R-deficient cell preparations, and MC3R-mediated anti-inflammatory pathway characterization in intestinal epithelial cell model systems.

Intestinal Inflammation and IBD Model Research

The published preclinical IBD mouse model data [Kannengiesser et al., 2008; PMID 18092346] support the investigation of KPV in intestinal inflammation research contexts. Research applications include cytokine profile characterization in intestinal epithelial cell preparations under LPS or cytokine stimulation and KPV treatment, myeloperoxidase activity assays in colonic tissue preparations, barrier integrity studies in intestinal epithelial cell monolayer preparations, and comparison of KPV delivery strategies (including intranasal) for colon-targeted anti-inflammatory research.

CNS Neuroinflammation Research

Alpha-MSH modulates CNS inflammatory responses via melanocortin receptors on neurons and glia; intranasal KPV is investigated as an approach to access these CNS targets. Research applications include NF-kB inhibition assays in microglial and astrocyte cell preparations, neuroinflammation model preparations investigating KPV anti-inflammatory activity in CNS cell systems, cytokine production assays in LPS-stimulated brain cell preparations, and comparative nose-to-brain delivery characterization of KPV in rodent olfactory model preparations.

Intranasal Anti-Inflammatory Peptide Delivery Research

KPV’s small molecular weight (~0.34 kDa), high water solubility, and absence of melanotropic effects make it a useful research tool for intranasal anti-inflammatory peptide delivery investigation. Research applications include nose-to-brain transport characterization for small hydrophilic tripeptides in rodent olfactory preparations, comparative nasal mucosal stability studies between KPV (free N-terminus) and acetylated anti-inflammatory peptides, and intranasal pharmacokinetic profiling of KPV in rodent model systems.

What are the Potential Side Effects?

Researchers in preclinical and in vitro settings have noted the following observations. Long-term safety and toxicity profiles remain incompletely characterized for the research-grade nasal spray formulation.

• No completed human clinical trials for KPV (any route): No published human clinical trials for KPV administered via any route,  intranasal, oral, topical, or parenteral, have been completed as of June 2026; all efficacy and safety context is derived from in vitro cell preparations and preclinical murine model studies
• Favorable preclinical safety profile in murine models: KPV treatment in DSS-colitis and CD45RBhi transfer colitis mouse model preparations did not produce notable adverse observations; body weight recovery was improved in KPV-treated animals versus vehicle controls [Kannengiesser et al., 2008; PMID 18092346]; this preclinical data does not constitute human safety evidence
• No melanotropic effects — confirmed advantage of KPV over full-length alpha-MSH: KPV lacks the melanotropic pharmacophore at positions 6-9 of alpha-MSH; it does not stimulate melanogenesis in melanocyte preparations; this is a pharmacological advantage for research use relative to alpha-MSH analogs with MCR agonist activity
• Nasal mucosal irritation (local administration context): As a small hydrophilic tripeptide administered to the nasal mucosa, KPV may produce mild mucosal irritation at high concentrations; this has not been characterized in published peer-reviewed nasal administration studies
• Absence of intranasal-specific safety data: No safety or tolerability data specific to the intranasal route of administration for KPV has been published in the peer-reviewed literature as of June 2026
• Anti-inflammatory activity at high concentrations — relevant to cell preparation design: KPV suppresses NF-kB activation and pro-inflammatory cytokine production at research concentrations; cell preparations with NF-kB-dependent readouts, cytokine assay systems, or immune cell functional assays will be pharmacologically influenced by KPV’s mechanism of action; researchers should design appropriate vehicle controls

No human safety or tolerability data has been established for KPV nasal spray via the intranasal route. These observations are derived from in vitro and preclinical murine model systems and should not be extrapolated to human or animal outcomes.

Risk & Handling

Handling Precautions

Standard laboratory PPE is required: nitrile gloves, a laboratory coat, and eye protection. The following nasal spray-specific precautions apply:

1. Do not direct the nasal spray actuator toward the face, eyes, or mucous membranes during handling, testing, or transfer. KPV is an anti-inflammatory tripeptide that inhibits NF-kB and modulates melanocortin receptor signaling; inadvertent intranasal self-exposure at research concentrations may produce NF-kB suppression at the nasal mucosa for which no human safety data has been established.
2. Handle the nasal spray solution in a clean laboratory environment. For aliquoting or analytical sampling, use a laminar flow cabinet.
3. The nasal spray solution is an aqueous formulation susceptible to microbial contamination. Handle under aseptic conditions. Discard if the solution appears cloudy, discolored, or shows particulate matter.

4. Avoid aerosol generation during any manipulation of the nasal spray solution.

Exposure Risks

Risk Tier: LOW

KPV has a favorable preclinical safety profile in murine model preparations. It lacks the melanotropic activity of full-length alpha-MSH, reducing risks associated with inadvertent pigmentation-pathway activation. No human safety data exists for any route of KPV administration. The anti-inflammatory mechanism (NF-kB inhibition, cytokine suppression) is biologically active at research concentrations and relevant to cell preparation design. Researchers should treat KPV with standard precautions appropriate to a biologically active anti-inflammatory research peptide.

Storage

In-use nasal spray: Store at 2-8°C. Use within 28 days of first actuation. Protect from light. Keep upright.

DO NOT FREEZE the ready-to-use nasal spray formulation. Freezing alters pH, buffer stability, and spray actuation properties.

Lyophilized bulk stock (if applicable): Store at -20°C in sealed, desiccated, light-protected containers. Avoid repeated freeze-thaw cycles.

Discard any solution that appears cloudy, discolored, or shows visible particulate matter.

FAQs

Q: How does intranasal KPV access anti-inflammatory research targets in preclinical models?

A: KPV (~0.34 kDa) has a small molecular weight favorable for nasal mucosal absorption via paracellular pathways, though its high hydrophilicity limits passive lipid-bilayer diffusion. The intranasal route bypasses hepatic first-pass metabolism and, via olfactory and trigeminal nerve transport [Wong et al., 2024; PMID 38441832], accesses CNS melanocortin receptors and NF-kB-dependent anti-inflammatory pathways in the brain. Peripheral anti-inflammatory targets are accessible via systemic absorption. No compound-specific intranasal pharmacokinetic data exists for KPV. The free N-terminal lysine in KPV is susceptible to aminopeptidase-mediated degradation at the nasal mucosa, which researchers should account for in delivery protocol design.

Q: What is the recommended storage and in-use shelf life for KPV nasal spray?

A: Sealed product should be stored at 2-8°C, protected from light. Once first actuated, in-use shelf life is 28 days at 2-8°C. DO NOT FREEZE the ready-to-use solution. Lyophilized bulk stock should be stored at -20°C in sealed, desiccated, light-protected conditions. Discard if the solution shows cloudiness, discoloration, or particulate matter.

Q: Is the KPV nasal spray formulation suitable for cell culture or in vitro assay systems?

A: The formulation is prepared in isotonic saline (0.9% NaCl, pH 6.5-7.4) without preservatives, compatible with standard cell culture pH ranges. Dilution into culture medium before application is recommended to normalize osmolarity. Researchers designing NF-kB-dependent assay systems, cytokine production assays, or immune cell functional studies should account for KPV’s mechanism of action and include appropriate vehicle controls. Researchers are responsible for confirming compatibility with their specific assay system.

Q: How does KPV differ from full-length alpha-MSH and from KdPT?

A: KPV (CAS 67727-97-3; MW 342.44 g/mol; H-Lys-Pro-Val-OH) is the C-terminal tripeptide of alpha-MSH at positions 11-13. It retains the anti-inflammatory activity of the parent peptide but lacks the melanotropic pharmacophore (positions 6-9) — meaning KPV does not stimulate melanogenesis. Full-length alpha-MSH (13 AA; MW approximately 1665 g/mol) has a broader activity profile including melanotropic effects and stronger MCR binding affinity. KdPT (Lys-D-Pro-Thr) is a structurally related anti-inflammatory tripeptide corresponding to residues 193-195 of IL-1beta, with overlapping but mechanistically distinct activity including IL-1 receptor type I interaction. KPV and KdPT are researched as complementary anti-inflammatory tripeptides, not as equivalents.

Q: What is the WADA status of KPV?

A: KPV is not explicitly named on the 2026 WADA Prohibited List. As a melanocortin-derived anti-inflammatory tripeptide, it does not fall within growth factor, peptide hormone, or other currently named prohibited substance categories. Researchers operating within WADA Code contexts should verify current status at GlobalDRO.com. RCDbio products are supplied for laboratory research purposes only.

Q: What is the FDA regulatory status of KPV?

A: KPV has no FDA-approved therapeutic indication for any formulation or route. It was classified as a 503A Category 2 bulk drug substance in late 2023, removed from Category 2 effective April 15, 2026, and is scheduled for PCAC evaluation on July 23, 2026 under Docket No. FDA-2026-N-2979. Removal from Category 2 does not authorize compounding; KPV remains unavailable for legitimate compounding until after the PCAC review and subsequent FDA rulemaking. The research-grade nasal spray is for laboratory research use only.

Q: Why is KPV’s anti-inflammatory activity considered at least partially independent of MC1R?

A: The study by Kannengiesser et al. (2008; PMID 18092346) demonstrated that KPV treatment rescued all animals in the MC1R-nonfunctional (MC1Re/e) mouse group from death during DSS colitis, while vehicle-treated MC1Re/e animals died. This indicates KPV produces significant anti-inflammatory effects even when MC1R signaling is completely abolished. The MC1R-independent mechanism is attributed primarily to direct NF-kB inhibition via IkB-alpha preservation, which operates intracellularly without requiring MCR engagement. Interaction with MC3R, which is expressed on intestinal epithelial cells and was not abolished in the MC1Re/e model, may also contribute.

Related Research Compounds

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

BPC-157 Nasal Spray — A stable gastric pentadecapeptide investigated for NO-system modulation, cytoprotective signaling, and mucosal healing in preclinical rodent preparations; shares the gastrointestinal mucosal anti-inflammatory and cytoprotective research context with KPV via non-overlapping mechanisms.

Reduced Glutathione (GSH) Nasal Spray — The primary intracellular antioxidant; complementary to KPV’s anti-inflammatory NF-kB inhibitory mechanism in oxidative stress and inflammatory pathway research.

MOTS-c Nasal Spray — A mitochondrial-derived peptide investigated for AMPK-mediated metabolic homeostasis and antioxidant response element (ARE) gene regulation; complementary cellular anti-inflammatory and stress response research tool.

All products listed are for laboratory and research purposes only.

References

1. Ichiyama, T., Sato, S., Okada, K., Catania, A., & Lipton, J.M. (2000). The neuroimmunomodulatory peptide alpha-MSH. Annals of the New York Academy of Sciences, 917, 221-226.

   https://pubmed.ncbi.nlm.nih.gov/11268347/

   DOI: https://doi.org/10.1111/j.1749-6632.2000.tb05386.x

2. Luger, T.A., & Brzoska, T. (2007). alpha-MSH related peptides: a new class of anti-inflammatory and immunomodulating drugs. Annals of the Rheumatic Diseases, 66(Suppl 3), iii52-iii55.

   https://pubmed.ncbi.nlm.nih.gov/17934097/

   DOI: https://doi.org/10.1136/ard.2007.079780

3. 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/

   DOI: https://doi.org/10.1002/ibd.20334

4. Wong, C.Y.J., Baldelli, A., Hoyos, C.M., et al. (2024). Insulin delivery to the brain via the nasal route: unraveling the potential for Alzheimer’s Disease therapy. Drug Delivery and Translational Research, 14(7), 1776-1793.

   https://pubmed.ncbi.nlm.nih.gov/38441832/

   DOI: https://doi.org/10.1007/s13346-024-01558-1

Research Transparency Note: Reference 1 is a review of alpha-MSH neuroimmunomodulatory activity establishing the NF-kB inhibition mechanism of KPV in peripheral and CNS model systems. Reference 2 is a class-level review establishing KPV as the primary anti-inflammatory pharmacophore of alpha-MSH and summarizing preclinical evidence across inflammatory disease models. Reference 3 is the primary peer-reviewed preclinical study of KPV, specifically, a murine IBD model study demonstrating anti-inflammatory activity in two independent colitis preparations, including MC1R-nonfunctional mice. Reference 4 provides class-level intranasal peptide delivery evidence. No human clinical trials for KPV administered via any route have been published as of June 2026. No published peer-reviewed study has specifically characterized intranasal pharmacokinetics or CNS delivery of KPV.

Disclaimer

KPV (Lysine-Proline-Valine) Nasal Spray 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.

ATTENTION: All RCDbio products are strictly for LABORATORY AND RESEARCH PURPOSES ONLY. They are not intended for human consumption, veterinary use, or any other non-research application. For queries, complaints, or support, contact support@rcdbio.co