Peptides · Tissue repair (under FDA review)

KPV

Tripeptide research ingredient with physician-request review.

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KPV molecular structure (Tripeptide (α-MSH fragment))

Why this needs to be personal

Why Personalized KPV

The evidence base for KPV is still preclinical. Published work centers on cell-culture and animal models of mucosal inflammation, skin injury, oral mucositis, and host-defense biology, without large randomized human efficacy trials.

Physicians may submit patient-specific prescription requests for KPV for pharmacy review. Certain preparations may be available now when clinically appropriate, lawfully prescribed, supported by patient-specific documentation, and approved by the dispensing pharmacy. Availability is determined case by case. This is not a consumer access promise; it is a clinical, sourcing, formulation, and regulatory review process. FDA has scheduled KPV-related bulk drug substances for discussion at the 23-24 Jul 2026 Pharmacy Compounding Advisory Committee meeting.

A physician-submitted pharmacy review is the regulated contrast to KPV sold through research-chemical channels, where identity, sterility, potency, clinical rationale, and patient follow-up are not tied to a licensed pharmacist.

In brief

KPV Explained

KPV is a short peptide made of three amino acids, lysine, proline, and valine. It is the tail end of a longer hormone called alpha-melanocyte-stimulating hormone (α-MSH), which the body produces from the same protein precursor as ACTH and beta-endorphin 8. Researchers became interested in KPV after observing that the full α-MSH hormone had anti-inflammatory effects and that the short C-terminal tripeptide retained much of that activity in laboratory studies.

KPV has no FDA approval in the United States. This ingredient is part of an evolving FDA review process. Physicians may submit patient-specific prescription requests for pharmacy review. Availability is determined case by case, and availability may change after FDA review, PCAC discussion, final agency action, or state-board guidance.

At a glance

Quick Facts About KPV

Category
Tripeptide (α-MSH C-terminal fragment, Lys-Pro-Val)
Active ingredient
Lysine-proline-valine, the three C-terminal residues (α-MSH 11, 13) of alpha-melanocyte-stimulating hormone, a 13-residue neuropeptide derived from POMC processing
FDA-approved branded forms
None. KPV is not an FDA-approved drug substance and has no approved branded product.
Evidence posture
Preclinical only, anti-inflammatory and antimicrobial activity in cell culture and rodent models of inflammatory bowel disease, wound healing, oral mucositis, and skin inflammation. No published randomized human efficacy trials.
FDA-approval status
Category 2, evolving FDA review process. Valid patient-specific prescription required; supporting clinical rationale may be requested.
Compounded under
Physicians may submit patient-specific prescription requests for pharmacy review. Availability is determined case by case.

Prescription review

Patient-Specific Prescription Only

Physicians may submit patient-specific prescription requests for KPV for pharmacy review. Certain preparations may be available now when clinically appropriate, lawfully prescribed, and approved by the dispensing pharmacy. Availability is determined case by case.

  • Made to order, not off a shelf. No batch sits in a warehouse waiting for buyers. Your prescription is what triggers the prep.
  • Named-patient label. The bottle carries your name. The batch records carry your prescription.
  • Dose, strength, and route chosen for you. A prescriber who knows your chart decides what gets compounded, not a manufacturer who set the strength for a trial population.
  • Licensed pharmacist on the hook. A real person, with a license that can be pulled, signs off on every prep. State inspectors check the facility.
  • Compounded drugs are not FDA-approved. They should not be evaluated using branded-drug trial data. Availability varies by state and prescribed medication.
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Real medicine, not gray market

How This Differs from a Research-Use-Only Website

A research-use-only website ships a vial from a warehouse. There is no prescription, no pharmacist, no facility inspection, and no way to recall the product if something is wrong with it. If the vial is mislabeled, contaminated, or under-potent, there is nobody whose license is at stake.

A 503A compounding pharmacy is the other thing. Your doctor writes the prescription. A licensed pharmacist, whose name is on the label, prepares the medicine in a facility the state inspects. If something goes wrong, there is a person and a license on the hook, and a documented chain of custody on every lot. That accountability is what makes it safe.

What it is

What is KPV?

KPV is a synthetic tripeptide composed of L-lysine, L-proline, and L-valine, corresponding to residues 11, 13 (the C-terminus) of alpha-melanocyte-stimulating hormone. α-MSH itself is a 13-amino-acid neuropeptide produced by post-translational processing of pro-opiomelanocortin (POMC), the same precursor that yields adrenocorticotropic hormone (ACTH), β-endorphin, and β-lipotropin. The full α-MSH molecule binds melanocortin receptors MC1R through MC5R; its central message sequence (residues 4, 10, HFRWGKP) carries the pigmentation-active pharmacophore 85.

Interest in the KPV C-terminal fragment originated with observations that anti-inflammatory effects of α-MSH could be reproduced by C-terminal fragments lacking the canonical melanocortin-receptor-binding message sequence 510. The Getting et al. 2003 mechanistic dissection demonstrated that the anti-inflammatory effect of α-MSH could be separated from the pigmentation pharmacophore and localized to the C-terminal tripeptide 1. Subsequent work characterized cytokine-suppressive activity in keratinocytes, intestinal epithelial cells, and bronchial epithelium 3411.

KPV is supplied as a synthetic peptide for research use and is not an FDA-approved drug substance. It has no FDA-approved branded product and no human prescribing-information label.

How it works

How KPV Works

Class
Tripeptide (α-MSH fragment)
First studied
1980s α-MSH research
Current status
Category 2, PCAC discussion scheduled 23-24 Jul 2026
Compounding category
Patient-specific 503A on physician request, pending broader FDA review

KPV's reported mechanism of action centers on inhibition of nuclear factor-kappa B (NF-κB) signaling and downstream suppression of proinflammatory cytokine production. In keratinocytes, intestinal epithelial cells, and bronchial epithelial cells, exposure to KPV reduces TNF-α-induced NF-κB nuclear translocation and lowers transcription of IL-1β, IL-6, IL-8, and other NF-κB-driven cytokines 3.

Whether KPV acts primarily through melanocortin receptors (MC1R, MC3R, MC5R) or through receptor-independent intracellular mechanisms has been investigated in multiple model systems and is not fully resolved. Getting and colleagues (2003) dissected the anti-inflammatory effect and reported that KPV retained activity in melanocortin-receptor-blockade conditions, supporting a partially receptor-independent intracellular mechanism 1. Land (2012) characterized KPV signaling in bronchial epithelium with a proposed contribution from MC3R agonism 11. Reviews acknowledge the dual mechanism and emphasize that the tripeptide retains anti-inflammatory activity in models where the parent α-MSH pharmacophore is not required 105 4.

In intestinal epithelial cells, KPV is internalized by the proton-coupled oligopeptide transporter PepT1, which is upregulated in inflamed colonic mucosa 612. PepT1-mediated uptake concentrates KPV at the site of inflammation and may underlie the colon-targeted activity reported in DSS- and TNBS-colitis models.

Research history

KPV Research History

Interest in α-MSH-derived peptides as anti-inflammatory agents grew through the 1990s and 2000s. Cutuli et al. (2000) characterized antimicrobial activity of α-MSH peptides including KPV-containing fragments against Staphylococcus aureus and Candida albicans, contributing to the dual anti-inflammatory and antimicrobial framing 2. Getting, Schiöth, and Perretti (2003) published the foundational mechanistic dissection showing that anti-inflammatory activity localized to the C-terminal tripeptide and could be separated from the pigmentation pharmacophore 1. Elliott et al. (2004) demonstrated cytokine-modulating activity of KPV in human keratinocyte cell lines, supporting a dermatologic rationale 3, and Kelly et al. (2006) reported that immobilized GKPV (α-MSH 10, 13, a closely related fragment) inhibits TNF-α-stimulated NF-κB activation 4.

The intestinal application emerged in the late 2000s. Dalmasso et al. (2008) reported that KPV is taken up by intestinal epithelial cells via PepT1 and that oral KPV reduced DSS-colitis severity in mice 6. Kannengiesser et al. (2008), working in the Luger group, extended the finding across murine DSS and CD4+CD45RB-high transfer colitis models, characterizing KPV as a candidate anti-inflammatory in inflammatory bowel disease 7. Laroui et al. (2010) translated the work into a colon-targeted nanoparticle delivery system that reduced colitis severity in mice at lower drug exposures than free KPV 9. Viennois et al. (2016) extended the framework to colitis-associated colorectal cancer in a mouse model and characterized the therapeutic benefit of PepT1-mediated KPV delivery 12. Xiao et al. (2017) developed a hyaluronic acid-functionalized nanoparticle system for oral KPV delivery that further improved efficacy in murine ulcerative colitis 13.

Concurrent dermatologic and ophthalmic work continued. Brzoska et al. (2008) published a comprehensive Endocrine Reviews summary of α-MSH and related tripeptides covering biochemistry, anti-inflammatory and protective effects in vitro and in vivo, and proposed therapeutic perspectives 8. Brzoska et al. (2010) extended this with the 'terminal signal' framework arguing that anti-inflammatory effects of α-MSH-related peptides operate beyond the canonical pharmacophore 10. Böhm and Luger (2019) reviewed the case for melanocortin peptides, including KPV, as future therapeutics in cutaneous wound healing 14. Recent hydrogel and nanoparticle delivery work 15 has continued to refine preclinical formulations for colitis and oral mucositis 151716. Reviews of the broader melanocortin system in IBD 18 and of tripeptides in wound healing 20 integrate KPV into the current preclinical evidence map; no randomized human efficacy trials are indexed.

Timeline

KPV Timeline

  1. 2000 Cutuli et al. (J Leukoc Biol) characterize antimicrobial activity of α-MSH peptides including KPV-containing fragments against S 2. aureus and C. albicans
  2. 2003 Getting, Schiöth, and Perretti (J Pharmacol Exp Ther) dissect anti-inflammatory activity of α-MSH and localize it to the C-terminal KPV tripeptide 1
  3. 2004 Elliott et al 3. (J Invest Dermatol) demonstrate KPV (α-MSH 11, 13) signaling in human keratinocyte cell lines
  4. 2006 Kelly et al 4. (Peptides) report that immobilized GKPV (α-MSH 10, 13) inhibits TNF-α-stimulated NF-κB activation
  5. 2007 Luger and Brzoska (Ann Rheum Dis) review α-MSH-related peptides as a class of anti-inflammatory and immunomodulating drug leads 5
  6. 2008 Dalmasso et al 6. (Gastroenterology) report that PepT1-mediated KPV uptake reduces intestinal inflammation in murine DSS colitis
  7. 2008 Kannengiesser et al 7. (Inflamm Bowel Dis) extend the IBD finding to multiple murine colitis models including the CD4+CD45RB-high transfer model
  8. 2008 Brzoska et al 8. (Endocr Rev) publish a comprehensive review of α-MSH and related tripeptides covering biochemistry, anti-inflammatory effects, and therapeutic perspectives
  9. 2010 Laroui et al 9. (Gastroenterology) describe a polysaccharide-hydrogel colon-targeted KPV nanoparticle delivery system that reduces murine colitis severity
  10. 2010 Brzoska et al 10. (Adv Exp Med Biol) advance the 'terminal signal' framework, anti-inflammatory effects of α-MSH-related peptides beyond the canonical pharmacophore
  11. 2012 Land (Int J Physiol Pathophysiol Pharmacol) characterizes KPV mechanism in human bronchial epithelial cells and proposes an MC3R-agonist contribution 11
  12. 2016 Viennois et al 12. (Cell Mol Gastroenterol Hepatol) extend the framework to colitis-associated colorectal cancer in mice; therapeutic benefit of PepT1-mediated KPV
  13. 2017 Xiao et al 13. (Mol Ther) develop a hyaluronic acid-functionalized oral nanoparticle delivery system for KPV in murine ulcerative colitis
  14. 2019 Böhm and Luger (Exp Dermatol) review melanocortin peptides including KPV as candidate cutaneous wound-healing therapeutics 14
  15. 2021 Sun et al 15. (ACS Biomater Sci Eng) report a self-cross-linked γ-polyglutamic acid hydrogel KPV formulation in rat TNBS ulcerative colitis
  16. 2021 Shao et al 16. (Biomater Sci) describe an in situ mucoadhesive hydrogel capturing KPV with anti-inflammatory and antibacterial effects in chemotherapy-induced oral mucositis
  17. 2022 Zhao et al 17. (Acta Biomater) characterize a KPV-binding double-network hydrogel that restores gut mucosal barrier in an inflamed mouse colon
  18. 2023 Gravina et al 18. (Cells) review the melanocortin system in inflammatory bowel diseases including KPV mechanism and therapeutic potential
  19. 2025 Sung et al 19. (Tissue Cell) report KPV mitigation of fine-dust-induced keratinocyte apoptosis and inflammation via MAPK/NF-κB modulation
  20. 2025 Adnan et al 20. (Int J Med Sci) review tripeptides, including KPV, in wound healing and skin regeneration

Natural role

Biological Role of KPV

Alpha-melanocyte-stimulating hormone is a 13-residue neuropeptide produced from POMC processing in the pituitary intermediate lobe, hypothalamus, skin keratinocytes, and immune cells. It binds the five melanocortin receptors (MC1R, MC5R) with distinct receptor-affinity and tissue-expression patterns and contributes to pigmentation (MC1R), energy balance (MC4R), exocrine function (MC5R), and immune-cell modulation (MC1R, MC3R, MC5R). Anti-inflammatory and immunomodulatory effects of α-MSH have been characterized across innate and adaptive immune cell types, with cytokine suppression and downregulation of NF-κB-driven transcription as recurring mechanisms 85.

The C-terminal tripeptide KPV (α-MSH 11, 13) retains a substantial fraction of the anti-inflammatory activity of the parent hormone despite lacking the central message sequence required for canonical melanocortin-receptor pharmacology 110. This dissociability of anti-inflammatory activity from pigmentation pharmacology motivated the original interest in KPV as a candidate small-peptide anti-inflammatory and underlies the current preclinical evidence map.

Compounded use

Compounded KPV (503A)

Physicians may submit patient-specific prescription requests for pharmacy review. For KPV, certain preparations may be available now when clinically appropriate, lawfully prescribed, and approved by the dispensing pharmacy. Availability is determined case by case and may depend on patient-specific documentation, ingredient status, source qualification, formulation feasibility, state requirements, and pharmacist judgment. The review starts with the evidence constraint: The evidence base for KPV is still preclinical. Published work centers on cell-culture and animal models of mucosal inflammation, skin injury, oral mucositis, and host-defense biology, without large randomized human efficacy trials.

This ingredient is part of an evolving FDA review process. RonanRx is monitoring FDA's PCAC process and any subsequent agency action. FDA has scheduled KPV-related bulk drug substances for discussion at the 23-24 Jul 2026 Pharmacy Compounding Advisory Committee meeting. Availability may change after FDA review, PCAC discussion, final agency action, or state-board guidance. For KPV, RonanRx ties that monitoring to the evidence limits described above and to any patient-specific documentation submitted by the prescriber.

Valid patient-specific prescription required. Supporting clinical rationale may be requested. Compounded medications are not FDA-approved. No consumer self-ordering, no office stock, no bulk dispensing. Requests for KPV are reviewed before any preparation is made or released. A physician-submitted pharmacy review is the regulated contrast to KPV sold through research-chemical channels, where identity, sterility, potency, clinical rationale, and patient follow-up are not tied to a licensed pharmacist.

Formulations and routes

KPV Formulations and Routes

FormConcentrationDescription
Research-grade synthetic tripeptide — KPV is available from peptide chemistry suppliers as a synthetic lysine-proline-valine tripeptide for research use. It is not an FDA-approved drug substance and is not available as a manufactured pharmaceutical product.21
Preclinical experimental formulations (not commercial products) — Published preclinical studies have used colon-targeted polysaccharide-hydrogel nanoparticles [laroui2010], hyaluronic acid-functionalized oral nanoparticles [xiao2017], γ-polyglutamic acid self-cross-linked hydrogels [sun2021], KPV-binding double-network hydrogels [zhao2022], and in situ mucoadhesive hydrogels [shao2021]. These are research formulations characterized in animal models, not commercial drug products.913151716

Dosing

KPV Dosing

No FDA-labeled or human-trial-validated dosing regimen exists for KPV 21. The published preclinical evidence base reports doses in mice and rats in units of µg per kg or per animal, delivered orally as free peptide, in colon-targeted nanoparticles or hydrogels, or topically, depending on the model system 91315. These animal-model doses do not translate to a clinical human regimen without human pharmacokinetic, dose-response, and safety data, none of which are published 6717.

RonanRx does not publish a consumer dosing schedule for KPV. Any request requires a valid patient-specific prescription, supporting clinical rationale, and pharmacist review. Route, strength, dosing interval, monitoring expectations, and dispensing quantity would be determined case by case from the prescriber's documentation and pharmacy feasibility review.

Doses listed are literature context, not patient instructions. Dosing decisions are made by the prescribing doctor and tailored to the individual patient.

Safety

KPV Safety

Safety overview

No published human safety data are indexed for KPV at the time of this review. Animal-model studies in mice and rats report short-term tolerability at the experimental doses used, with no consistent organ-toxicity signal across the colitis, oral mucositis, and wound-healing literature 131516. Absence of acute toxicity in short-duration rodent studies does not establish human safety; longer-term toxicology, immunogenicity, reproductive toxicity, carcinogenicity, and pharmacokinetic data have not been published.

Because KPV is on FDA's Category 2 bulk-substance list for 503A compounding 21, FDA has identified either safety concerns or an information gap that must be evaluated. Clinicians considering KPV-containing preparations from non-503A sources should be aware that such products are not subject to FDA bulk-substance review, USP <797> sterility standards, or pharmacist verification of identity and potency 7617. Availability through RonanRx is determined case by case after pharmacy review.

Published reviews of α-MSH-derived peptides as a class describe a generally favorable preclinical safety profile relative to small-molecule anti-inflammatories, attributed to the short peptide structure and rapid catabolism 8510; these reviews are not equivalent to human safety data for KPV specifically.

Contraindications

Honest gap. No published human contraindications for KPV are indexed. KPV is not an FDA-approved drug substance and has no prescribing-information label. FDA Category 2 bulk-substance status precludes 503A compounding pending reclassification.

Searched: PubMed, FDA bulk-substance review documents on 2026-05-11 · terms KPV tripeptide AND (contraindication OR contraindicated OR hypersensitivity).

Drug interactions

Honest gap. No published human drug-interaction studies for KPV are indexed at the time of review. PepT1 transporter-mediated uptake in intestinal epithelium [dalmasso2008] suggests theoretical co-substrate or inhibitor interactions with other PepT1 substrates (e.g., β-lactam antibiotics, ACE inhibitors with peptidomimetic structure) but no clinical interaction studies have been published.

Searched: PubMed, DailyMed on 2026-05-11 · terms KPV tripeptide AND (drug interaction OR pharmacokinetic interaction).

Adverse events

Honest gap. No published human adverse-event series are indexed for KPV. Preclinical rodent studies in colitis, oral mucositis, and wound-healing models report short-term tolerability without consistent organ-toxicity signals at experimental doses, but human adverse-event data are absent.

Searched: PubMed, FDA Adverse Event Reporting System (FAERS) on 2026-05-11 · terms KPV tripeptide AND (adverse event OR adverse effect OR side effect).

Monitoring

Monitoring KPV Therapy

No RonanRx-specific monitoring protocol has been established for KPV. If a patient-specific prescription is submitted, supporting clinical rationale may be requested, and monitoring expectations would be reviewed case by case against the published evidence, route, sterile or nonsterile status, concomitant therapies, and patient risk factors.

Special populations

KPV in Special Populations

Pregnancy

No FDA-recognized use guidance for KPV in this population is established. Any patient-specific request would require prescriber rationale, patient-specific risk review, and pharmacist approval before dispensing.

Lactation

No published human lactation data for KPV are indexed 21.

Pediatric

No published pediatric data for KPV are indexed 21.

Geriatric

No published geriatric data for KPV are indexed 21.

Renal impairment

No published renal-impairment data for KPV are indexed 21.

Hepatic impairment

No published hepatic-impairment data for KPV are indexed 21.

Evidence quality

KPV Evidence Quality

The KPV evidence base is preclinical. Indexed PubMed literature consists of mechanistic in vitro studies in keratinocyte, intestinal epithelial, and bronchial epithelial cell lines, rodent models of inflammatory bowel disease using DSS and TNBS chemical colitis induction or CD4+CD45RB-high transfer protocols, colon-targeted nanoparticle and hydrogel oral delivery systems characterized in murine colitis 91317, rodent oral mucositis models 16, keratinocyte and corneal wound-healing assays 319, and narrative and systematic reviews summarizing the class. Cutuli et al 1541. (2000) and related work characterized antimicrobial activity against S 8510. aureus and C 7612. albicans 2 1820.

No published randomized controlled human trials of KPV efficacy are indexed in PubMed. No published human pharmacokinetic, pharmacodynamic, or dose-response studies are indexed. No FDA-approved branded product exists. KPV is currently on FDA's Category 2 bulk-substance list for 503A compounding 21 1411. The mechanistic and preclinical evidence is internally consistent and biologically plausible but does not constitute clinical evidence; any clinical claim about KPV in humans extrapolates from rodent and cell-culture data and should be framed as preclinical-grade.

Major studies

Major KPV Clinical Studies

StudyDesignParticipantsDurationFinding
Getting et al. (2003, J Pharmacol Exp Ther), Anti-inflammatory dissection of α-MSH In vitro and rodent in vivo dissection of α-MSH anti-inflammatory activity, comparing the full hormone, the core message sequence, and the C-terminal KPV tripeptide — — Anti-inflammatory activity localizes to the C-terminal KPV tripeptide and is at least partially independent of the canonical melanocortin-receptor-binding pharmacophore; receptor-blockade experiments support a receptor-independent intracellular mechanism contribution 1
Cutuli et al. (2000, J Leukoc Biol), Antimicrobial α-MSH peptides In vitro antimicrobial assays of α-MSH and C-terminal fragment peptides against bacterial and fungal targets — — α-MSH and KPV-containing C-terminal fragments exhibit antimicrobial activity against S 2. aureus and C. albicans at micromolar concentrations
Elliott et al. (2004, J Invest Dermatol), Keratinocyte signaling In vitro studies in human keratinocyte cell lines comparing α-MSH, MSH 11, 13 (KPV), and ACTH signaling — — KPV reproduces a substantial fraction of α-MSH signaling effects in human keratinocyte cell lines, supporting a dermatologic rationale for the tripeptide fragment 3
Kelly et al. (2006, Peptides), Immobilized GKPV inhibits NF-κB In vitro mechanism study with immobilized α-MSH 10, 13 (GKPV) on TNF-α-stimulated NF-κB activation in cell culture — — Immobilized GKPV inhibits TNF-α-stimulated NF-κB nuclear translocation and downstream cytokine transcription 4
Dalmasso et al. (2008, Gastroenterology), PepT1-mediated KPV in DSS colitis In vitro PepT1 transporter studies in intestinal epithelial cells and in vivo DSS-colitis model in mice receiving oral KPV — — KPV is taken up by intestinal epithelial cells via PepT1; oral KPV reduces colitis severity, neutrophil infiltration, and proinflammatory cytokine expression in DSS-colitis mice 6
Kannengiesser et al. (2008, Inflamm Bowel Dis), KPV in multiple murine IBD models Murine DSS-colitis and CD4+CD45RB-high transfer colitis models with oral or systemic KPV administration — — KPV reduces colitis severity, mucosal cytokine production, and histologic injury across DSS and adoptive-transfer colitis models, anti-inflammatory potential across mechanistically distinct IBD models 7
Laroui et al. (2010, Gastroenterology), Colon-targeted KPV nanoparticles Polysaccharide-hydrogel-encapsulated KPV nanoparticles in murine DSS colitis — — Colon-targeted KPV nanoparticles reduce colitis severity at substantially lower drug exposures than free KPV, supporting the local-delivery rationale 9
Land (2012, Int J Physiol Pathophysiol Pharmacol), Bronchial epithelial KPV mechanism In vitro mechanism study in human bronchial epithelial cells with KPV and melanocortin-receptor-selective agonists — — KPV inhibits cellular and systemic inflammation signaling in bronchial epithelium with proposed contribution from MC3R agonism 11
Viennois et al. (2016, Cell Mol Gastroenterol Hepatol), PepT1 in CAC Murine model of colitis-associated colorectal cancer with intestinal-epithelial-specific PepT1 modulation and therapeutic KPV — — PepT1 plays a critical role in promoting colitis-associated cancer; KPV delivered via PepT1 provides therapeutic benefit in the murine CAC model 12
Xiao et al. (2017, Mol Ther), Hyaluronic-acid-functionalized KPV nanoparticles Orally administered hyaluronic-acid-functionalized nanoparticle KPV formulation in a murine ulcerative colitis model — — HA-functionalized oral nanoparticles efficiently target inflamed colon and alleviate ulcerative colitis in mice at lower systemic drug exposures than free peptide 13
Sun et al. (2021, ACS Biomater Sci Eng), γ-PGA hydrogel KPV in TNBS colitis Self-cross-linked cysteamine-grafted γ-polyglutamic acid hydrogel KPV formulation in rat TNBS-colitis model — — Hydrogel-stabilized KPV reduces TNBS-colitis severity in rats with improved retention at the inflamed mucosa relative to free peptide 15
Shao et al. (2021, Biomater Sci), Mucoadhesive KPV hydrogel for oral mucositis In situ mucoadhesive hydrogel capturing KPV in a chemotherapy-induced oral mucositis model in rodents — — Mucoadhesive KPV hydrogel produces anti-inflammatory, antibacterial, and tissue-repair effects in chemotherapy-induced oral mucositis 16
Zhao et al. (2022, Acta Biomater), KPV-binding hydrogel restores gut barrier KPV-binding double-network hydrogel in an inflamed murine colon model — — The KPV-binding double-network hydrogel restores gut mucosal barrier function and reduces inflammation in inflamed colon 17
Sung et al. (2025, Tissue Cell), Keratinocyte fine-dust injury In vitro keratinocyte study of fine-dust-induced apoptosis and inflammation with KPV intervention — — KPV mitigates fine-dust-induced keratinocyte apoptosis and inflammation by regulating oxidative stress and modulating MAPK/NF-κB signaling 19
Brzoska et al. (2008, Endocrine Reviews), α-MSH and related tripeptides Comprehensive narrative review covering biochemistry, in vitro and in vivo anti-inflammatory and protective effects of α-MSH and related tripeptides including KPV — — Integrates the preclinical evidence base for α-MSH-derived peptides as anti-inflammatory and immunomodulatory candidates with proposed therapeutic perspectives in immune-mediated inflammatory disease 8
Böhm and Luger (2019, Exp Dermatol), Melanocortin peptides for wound healing Narrative review of melanocortin peptides, including KPV, as candidate cutaneous wound-healing therapeutics — — Reviews the preclinical case for melanocortin peptides in cutaneous wound healing and identifies KPV among the most-studied C-terminal fragments; clinical translation remains preclinical-stage 14

Pharmacology

KPV Pharmacokinetics & Pharmacodynamics

Pharmacokinetics

No published human pharmacokinetic data for KPV are indexed at the time of review. The tripeptide is small (molecular weight 342.4 g/mol for the free peptide) and is expected to be rapidly catabolized by serum and tissue peptidases. In intestinal epithelial cells the H+-coupled di- and tripeptide transporter PepT1 mediates active uptake, with PepT1 expression upregulated in inflamed colonic mucosa, the molecular basis for the inflammation-targeted activity reported in murine colitis models 612.

Preclinical formulation work has focused on protecting KPV from upper-GI proteolysis and concentrating delivery at the inflamed mucosa: polysaccharide-hydrogel nanoparticles 9, hyaluronic-acid-functionalized oral nanoparticles 13, γ-polyglutamic acid hydrogels 15, double-network hydrogels 17, and mucoadhesive in situ gels 16. These formulations are research tools rather than commercial products.

Pharmacodynamics

Reported pharmacodynamic endpoints in preclinical studies include NF-κB-driven proinflammatory cytokine expression (TNF-α, IL-1β, IL-6, IL-8), histologic colitis severity scores (disease activity index, microscopic injury), neutrophil infiltration markers (myeloperoxidase activity), epithelial barrier integrity (transepithelial electrical resistance, FITC-dextran permeability), and wound-closure or re-epithelialization rates in skin and oral mucosa models 7413. No validated human pharmacodynamic biomarker for KPV exists 61716.

RonanRx operations

KPV Compounding & Operations

503A compounding

Physicians may submit patient-specific prescription requests for pharmacy review. For KPV, certain preparations may be available now when clinically appropriate, lawfully prescribed, and approved by the dispensing pharmacy. Availability is determined case by case and may depend on patient-specific documentation, ingredient status, source qualification, formulation feasibility, state requirements, and pharmacist judgment. The review starts with the evidence constraint: The evidence base for KPV is still preclinical. Published work centers on cell-culture and animal models of mucosal inflammation, skin injury, oral mucositis, and host-defense biology, without large randomized human efficacy trials.

This ingredient is part of an evolving FDA review process. RonanRx is monitoring FDA's PCAC process and any subsequent agency action. FDA has scheduled KPV-related bulk drug substances for discussion at the 23-24 Jul 2026 Pharmacy Compounding Advisory Committee meeting. Availability may change after FDA review, PCAC discussion, final agency action, or state-board guidance. For KPV, RonanRx ties that monitoring to the evidence limits described above and to any patient-specific documentation submitted by the prescriber.

Valid patient-specific prescription required. Supporting clinical rationale may be requested. Compounded medications are not FDA-approved. No consumer self-ordering, no office stock, no bulk dispensing. Requests for KPV are reviewed before any preparation is made or released. A physician-submitted pharmacy review is the regulated contrast to KPV sold through research-chemical channels, where identity, sterility, potency, clinical rationale, and patient follow-up are not tied to a licensed pharmacist.

Pharmacist review

For KPV, the pharmacist review starts before any preparation is made. Valid patient-specific prescription required. Supporting clinical rationale may be requested. The pharmacist reviews ingredient status, sourcing, formulation feasibility, state requirements, patient-specific documentation, and whether dispensing is appropriate case by case.

Quality and traceability

If a KPV preparation is approved after pharmacy review, RonanRx applies source documentation, formulation records, lot traceability, release checks, and storage controls appropriate to the actual dosage form. Research-use vial storage practices do not substitute for pharmacy-assigned storage, beyond-use dating, sterility controls when applicable, or recallable batch records. The patient-specific framework and quality controls are documented in the cited compounding references 222423.

Cold chain

If a KPV preparation is approved after pharmacy review, RonanRx applies source documentation, formulation records, lot traceability, release checks, and storage controls appropriate to the actual dosage form. Research-use vial storage practices do not substitute for pharmacy-assigned storage, beyond-use dating, sterility controls when applicable, or recallable batch records.

FAQ

Frequently Asked Questions About KPV

Can physicians request KPV through RonanRx?

Physicians may submit patient-specific prescription requests for pharmacy review. Certain preparations may be available now when clinically appropriate, lawfully prescribed, and approved by the dispensing pharmacy. Availability is determined case by case. Compounded medications are not FDA-approved, and no consumer self-ordering, office stock, or bulk dispensing is offered.2122

What is KPV?

KPV is a synthetic tripeptide of lysine, proline, and valine, the three C-terminal residues (positions 11, 13) of alpha-melanocyte-stimulating hormone (α-MSH), a 13-residue POMC-derived neuropeptide 81. The C-terminal fragment retains a substantial fraction of α-MSH's anti-inflammatory activity in preclinical models despite lacking the canonical melanocortin-receptor-binding message sequence 5.

Is there human evidence for KPV?

Not in the form of published randomized human efficacy trials 1614. The PubMed-indexed evidence base for KPV is preclinical: mechanistic in vitro studies in keratinocyte, intestinal, and bronchial epithelial cells; murine and rat models of DSS- and TNBS-colitis, colitis-associated cancer, oral mucositis, and wound healing; and class reviews of α-MSH-derived peptides 7613.

Why is KPV interesting to IBD researchers?

Kannengiesser et al. (2008) reported anti-inflammatory activity of KPV across murine DSS-colitis and CD4+CD45RB-high transfer colitis 712. Dalmasso et al. (2008) showed that KPV is taken up by intestinal epithelial cells via the PepT1 transporter, which is upregulated in inflamed colonic mucosa, providing a mechanistic rationale for inflammation-targeted activity 6. Multiple groups have since developed colon-targeted nanoparticle and hydrogel formulations characterized in rodent colitis 13. All of this work is preclinical.

Could KPV move from FDA Category 2 to Category 1?

Possibly, if the agency receives sufficient evidence to evaluate safety and clinical utility. The Category 2 designation reflects FDA's current assessment of the evidence base; it is not a permanent finding. RonanRx will track future bulk-substance review revisions and will reconsider compounding only if and when KPV is moved to Category 1 21.

Where does KPV fit in the α-MSH and melanocortin literature?

KPV is the C-terminal tripeptide of α-MSH (residues 11, 13) 11. The full α-MSH binds melanocortin receptors MC1R, MC5R; the C-terminal tripeptide retains anti-inflammatory activity through partially receptor-independent intracellular pathways with proposed contributions from MC3R and MC5R, as documented in the Brzoska Endocrine Reviews summary and subsequent mechanism studies 8101.

Clinician resource

Download the KPV Clinical Monograph (PDF)

The full white paper covers every section on this page plus chemical identity, evidence grading, indication-by-indication summaries, research gaps, and reference appendix. Suitable for sharing with prescribing doctors and pharmacist reviewers.

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References

References

  1. [getting2003] Getting SJ, Schiöth HB, Perretti M. Dissection of the anti-inflammatory effect of the core and C-terminal (KPV) alpha-melanocyte-stimulating hormone peptides. Journal of Pharmacology and Experimental Therapeutics. 2003. PMID 12750433. (accessed 2026-05-11)
  2. [cutuli2000] Cutuli M, Cristiani S, Lipton JM, Catania A. Antimicrobial effects of alpha-MSH peptides. Journal of Leukocyte Biology. 2000. PMID 10670585. (accessed 2026-05-11)
  3. [elliott2004] Elliott RJ, Szabo M, Wagner MJ, Kemp EH, MacNeil S, Haycock JW. alpha-Melanocyte-stimulating hormone, MSH 11-13 KPV and adrenocorticotropic hormone signalling in human keratinocyte cells. Journal of Investigative Dermatology. 2004. PMID 15102092. (accessed 2026-05-11)
  4. [kelly2006] Kelly JM, Moir AJ, Carlson K, Yang Y, MacNeil S, Haycock JW. Immobilized alpha-melanocyte stimulating hormone 10-13 (GKPV) inhibits tumor necrosis factor-alpha stimulated NF-kappaB activity. Peptides. 2006. PMID 16274845. (accessed 2026-05-11)
  5. [luger2007] Luger TA, Brzoska T. alpha-MSH related peptides: a new class of anti-inflammatory and immunomodulating drugs. Annals of the Rheumatic Diseases. 2007. PMID 17934097. (accessed 2026-05-11)
  6. [dalmasso2008] Dalmasso G, Charrier-Hisamuddin L, Nguyen HT, Yan Y, Sitaraman S, Merlin D. PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation. Gastroenterology. 2008. PMID 18061177. (accessed 2026-05-11)
  7. [kannengiesser2008] Kannengiesser K, Maaser C, Heidemann J, Luegering A, Ross M, Brzoska T, Bohm M, Luger TA, Domschke W, Kucharzik T. Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease. Inflammatory Bowel Diseases. 2008. PMID 18092346. (accessed 2026-05-11)
  8. [brzoska2008] Brzoska T, Luger TA, Maaser C, Abels C, Böhm M. 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. 2008. PMID 18612139. (accessed 2026-05-11)
  9. [laroui2010] Laroui H, Dalmasso G, Nguyen HT, Yan Y, Sitaraman SV, Merlin D. Drug-loaded nanoparticles targeted to the colon with polysaccharide hydrogel reduce colitis in a mouse model. Gastroenterology. 2010. PMID 19909746. (accessed 2026-05-11)
  10. [brzoska2010] Brzoska T, Böhm M, Lügering A, Loser K, Luger TA. Terminal signal: anti-inflammatory effects of α-melanocyte-stimulating hormone related peptides beyond the pharmacophore. Advances in Experimental Medicine and Biology. 2010. PMID 21222263. (accessed 2026-05-11)
  11. [land2012] Land SC. 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. 2012. PMID 22837805. (accessed 2026-05-11)
  12. [viennois2016] Viennois E, Ingersoll SA, Ayyadurai S, Zhao Y, Wang L, Zhang M, Han MK, Garg P, Xiao B, Merlin D. Critical role of PepT1 in promoting colitis-associated cancer and therapeutic benefits of the anti-inflammatory PepT1-mediated tripeptide KPV in a murine model. Cellular and Molecular Gastroenterology and Hepatology. 2016. PMID 27458604. (accessed 2026-05-11)
  13. [xiao2017] Xiao B, Xu Z, Viennois E, Zhang Y, Zhang Z, Zhang M, Han MK, Kang Y, Merlin D. Orally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis. Molecular Therapy. 2017. PMID 28143741. (accessed 2026-05-11)
  14. [bohm2019] Böhm M, Luger T. Are melanocortin peptides future therapeutics for cutaneous wound healing?. Experimental Dermatology. 2019. PMID 30661264. (accessed 2026-05-11)
  15. [sun2021] Sun J, Xue P, Liu J, Huang L, Lin G, Ran K, Yang J, Lu C, Zhao YZ, Xu HL. Self-Cross-Linked Hydrogel of Cysteamine-Grafted γ-Polyglutamic Acid Stabilized Tripeptide KPV for Alleviating TNBS-Induced Ulcerative Colitis in Rats. ACS Biomaterials Science and Engineering. 2021. PMID 34547895. (accessed 2026-05-11)
  16. [shao2021] Shao W, Chen R, Lin G, Ran K, Zhang Y, Yang J, Pan H, Shangguan J, Zhao Y, Xu H. In situ mucoadhesive hydrogel capturing tripeptide KPV: the anti-inflammatory, antibacterial and repairing effect on chemotherapy-induced oral mucositis. Biomaterials Science. 2021. PMID 34846053. (accessed 2026-05-11)
  17. [zhao2022] Zhao Y, Xue P, Lin G, Tong M, Yang J, Zhang Y, Ran K, Zhuge D, Yao Q, Xu H. A KPV-binding double-network hydrogel restores gut mucosal barrier in an inflamed colon. Acta Biomaterialia. 2022. PMID 35245681. (accessed 2026-05-11)
  18. [gravina2023] Gravina AG, Pellegrino R, Durante T, Palladino G, Imperio G, D'Amico G, Trotta MC, Dallio M, Romeo M, D'Amico M, Federico A. The Melanocortin System in Inflammatory Bowel Diseases: Insights into Its Mechanisms and Therapeutic Potentials. Cells. 2023. PMID 37508552. (accessed 2026-05-11)
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  21. [fda_cat2_peptides] U.S. Food and Drug Administration. Bulk Drug Substances Used in Compounding Under Section 503A of the FD&C Act. FDA Drug Compounding. 2024. https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act (accessed 2026-05-11)
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