KPV
Research PeptideAlso known as: Lys-Pro-Val · α-MSH(11-13) · alpha-MSH C-terminal tripeptide · MSH 11-13
Animal Only
No published human clinical trials exist for KPV in any indication. All therapeutic claims are derived from mouse colitis models (DSS-, TNBS-, and AOM/DSS-induced), rabbit corneal wound-healing models, and human-derived cell lines — not from completed human trials. The two research groups that produced most of the KPV-specific literature (the Catania lab at Milan for α-MSH fragment anti-inflammatory signaling, and the Merlin lab at Georgia State for PepT1-mediated colitis work) do most of the heavy lifting, and independent replication of the headline therapeutic findings has not been identified. A separate identity risk compounds the evidence problem: some vendors sell the N-acetylated, C-amidated form (Ac-KPV-NH2, ~383 Da) under the same "KPV" label as the free acid (H-KPV-OH, ~342 Da) — these are structurally different compounds with different properties, and buyers cannot distinguish them without mass-spectrometry confirmation. The FDA removed KPV from Category 2 of the interim 503A bulks list in April 2026 (via nominator withdrawal, not a safety determination) and has scheduled Pharmacy Compounding Advisory Committee review for July 23–24, 2026; until then, KPV is not legal for 503A compounding.
KPV is a fragment of α-MSH — but it is NOT Melanotan, and the mechanism is completely different
Online discussions routinely treat KPV as 'like Melanotan' or 'a type of MSH peptide' — a framing that is mechanistically wrong and masks KPV's actual anti-inflammatory mechanism. KPV is the C-terminal tripeptide of α-MSH (residues 11–13), but it does NOT activate MC1-R, MC3-R, or MC4-R at pharmacological concentrations — demonstrated directly in MC1-R-deficient mice (where KPV's anti-inflammatory effect was preserved) and via MC3/4-R antagonist blockade (which also did not block the effect). KPV's documented anti-inflammatory mechanism is PepT1-mediated intracellular NF-κB suppression in intestinal epithelium, not melanocortin receptor agonism. That means no tanning, no MC4-R-mediated sexual arousal, no appetite dysregulation, no ghrelin-axis involvement. Melanotan I/II and KPV should not be discussed as functionally equivalent or as members of the same therapeutic class — the mechanism is genuinely different, and the safety profile differs as a direct consequence.
Research use only. Not approved for human consumption in any jurisdiction listed here unless the Regulatory Status table below explicitly states otherwise.
Evidence Tier
Animal Only
Human Studies
3
FDA Status
503A Category 3
WADA Status
Not listed
Mol. Weight
342.41 Da
Last Reviewed
Apr 22, 2026
Claimed benefits by evidence tier
Column header colour matches the tier
Animal Only8
- Reduces intestinal inflammation in IBD (ulcerative colitis, Crohn's)
- Inhibits NF-κB inflammatory signaling at nanomolar concentrations
- Accelerates corneal epithelial wound healing
- Reduces skin inflammation (atopic dermatitis, eczema, psoriasis)
- May reduce colitis-associated colorectal cancer risk
- Systemic anti-inflammatory activity
- Does not activate melanocortin receptors (no tanning, no MC4-R effects)
- Immune system "balancing" / immunomodulation
Anecdotal1
- Repairs gut permeability / "leaky gut"
Unsupported1
- Anti-aging / longevity effects
Regulatory watch
FDA Pharmacy Compounding Advisory Committee meeting — KPV (free base) and KPV acetate on the agenda for 503A Bulks List review. Meeting July 23–24, 2026 at FDA White Oak Campus, Silver Spring, MD. Public docket FDA-2025-N-6895 open through July 22, 2026.
Most consequential near-term regulatory event for KPV in the US. PCAC could recommend: (a) adding KPV to the 503A Bulks List — giving compounding pharmacies a legal pathway for prescription-based preparation; (b) returning KPV to Category 2; or (c) further study. The committee's recommendation is advisory; FDA is not bound to follow it but historically does. Until either PCAC recommends inclusion and FDA acts on it, KPV is not on the 503A positive list and cannot be legally compounded under 503A. Same docket as BPC-157 and TB-500 — all three peptides are on the July 23–24 agenda.
Expected 2026-07-24 · Docket FDA-2025-N-6895 · FDA-2025-N-6895FDA
Verification of the April 15, 2026 FDA 503A Categories Update (fda.gov/media/94155/download) — confirming whether KPV is among the 12 peptides removed from Category 2 effective April 22, 2026.
Primary FDA PDF was not directly accessible during research. Secondary sources suggest KPV is among the 12 Category-2 removals, but verification against the primary document is required before acting on any specific US regulatory claim for this compound.
· FDA
ClinicalTrials.gov — absence of any registered human trial for KPV. Any future Phase I/II registration would be a material development.
As of April 2026, no registered human trials for KPV or Lys-Pro-Val were identified. Absence of a Phase I/II program is a significant impediment to any future regulatory approval pathway. Watch item.
· Source
Vendors selling KPV
Found 11 vendors currently offering KPV in their catalog.
Verified Peptides
COA Coverage
138/138
100%
✓ HPLC✓ MS✓ Endo✓ Ster— Metals
🇺🇸Soma Chems
USA
COA Coverage
60/64
94%
✓ HPLC✓ MS✓ Endo— Ster— Metals
🇺🇸Sports Technology Labs
USA
COA Coverage
57/61
93%
✓ HPLC✓ MS— Endo— Ster— Metals
Vida Labz
COA Coverage
48/49
98%
✓ HPLC— MS— Endo— Ster— Metals
Panda Peptides
COA Coverage
33/37
89%
✓ HPLC— MS— Endo— Ster— Metals
Peptide Partners
COA Coverage
29/35
83%
✓ HPLC— MS✓ Endo✓ Ster✓ Metals
🇪🇺Particle Peptides
Slovakia
COA Coverage
25/25
100%
✓ HPLC✓ MS✓ Endo✓ Ster✓ Metals
Amino Amigos
COA Coverage
10/39
26%
✓ HPLC✓ MS— Endo— Ster— Metals
🇺🇸BioLongevityLabs
USA
COA Coverage
43/89
48%
✓ HPLC✓ MS✓ Endo✓ Ster— Metals
🇺🇸Core Peptides
USA
COA Coverage
18/103
17%
✓ HPLC✓ MS— Endo— Ster— Metals
Blue Sky Peptide
No verified COAs
COA Coverage
0/45
0%
— HPLC— MS— Endo— Ster— Metals
All KPV products
Every KPV product across 11 verified vendors — sorted by vendor trust tier, then by COA purity (quantified reports beat unquantified), then by most recent COA date.
| Vendor | Product | Size | COA Date | Purity | Lab | COA |
|---|---|---|---|---|---|---|
| Sports Technology Labs Trusted | KPV Peptide 5 mg | 5mg | 2025-10-17 | 99.90% | MZ BiolabsTier 2 — Functional | View |
| Soma Chems Trusted | KPV | — | 2026-02-13 | 99.83% | Freedom Diagnostics TestingTier 4 — Unverifiable | View |
| Particle Peptides Trusted | KPV 5mg | 5mg | 2025-12-17 | 99.30% | LiquilabsTier 3 — Limited | View |
| Panda Peptides Trusted | KPV 10mg | 10mg | — | 99.22% | Janoshik AnalyticalTier 1 — Established | View |
| Peptide Partners Trusted | KPV (10mg vials) | 10mg | 2026-01-28 | — | TrustPointe AnalyticsTier 2 — Functional | View |
| Verified Peptides Trusted | KPV Peptide | — | 2025-10-30 | — | Janoshik AnalyticalTier 1 — Established | View |
| Vida Labz Trusted | KPV 12MG | 12mg | — | — | Janoshik AnalyticalTier 1 — Established | View |
| Amino Amigos Acceptable | KPV 10mg | 10mg | — | — | — | — |
| BioLongevityLabs Unrated | KPV (10mg) | 10mg | — | 99.00% | Bio RegenTier 4 — Unverifiable | View |
| Blue Sky Peptide Unrated | KPV 5mg | 5mg | — | — | — | — |
| Core Peptides Unrated | KPV (4mg) | 4mg | — | — | — | View |
About this peptide
Plain English
Your body produces a hormone called alpha-melanocyte-stimulating hormone (α-MSH) that, among other things, helps control inflammation. Scientists discovered that just the last three amino acids of this hormone — lysine, proline, and valine, abbreviated KPV — carry most of its anti-inflammatory activity without triggering the pigmentation effects associated with the full hormone. Research has focused on mouse models of gut inflammation (Crohn's, ulcerative colitis) and rabbit models of corneal wounds, where KPV accelerated healing. No human clinical trials have been completed. KPV is not approved by any regulatory agency as a therapeutic drug, and the FDA is scheduled to formally evaluate it for compounding pharmacy use in July 2026.
Technical
KPV (L-Lys-L-Pro-L-Val; MW ~342 Da, free acid) is the C-terminal tripeptide of α-MSH, an endogenous tridecapeptide product of POMC cleavage. Unlike α-MSH, KPV does NOT activate canonical melanocortin receptors (MC1-R, MC3-R, MC4-R) at physiologically relevant concentrations — mechanistic differentiation established by Bhardwaj 2003 using MC3/4-R antagonist blockade and MC1-R-deficient mice. The primary documented mechanism in intestinal inflammation is transport-dependent: the proton-coupled di/tripeptide transporter PepT1 (SLC15A1), normally confined to small intestinal enterocytes but markedly upregulated in colonic epithelium and immune cells during active IBD, mediates KPV uptake; once intracellular, KPV inhibits NF-κB nuclear translocation and MAPK activation at nanomolar concentrations. A second proposed mechanism involves antagonism at IL-1β receptor binding sites — particularly characterized for the D-Pro diastereomer Lys-D-Pro-Val. In corneal epithelium, NO-mediated facilitation of re-epithelialization has been documented in rabbits. All mechanistic work is preclinical; human pharmacokinetics, bioavailability, and pharmacodynamics have not been published. Critically, vendor labeling is inconsistent: the free acid (H-KPV-OH, ~342 Da) and the N-acetylated, C-amidated form (Ac-KPV-NH2, ~383 Da) are structurally distinct compounds sold under the same 'KPV' name — buyers cannot distinguish without mass spectrometry.
Mechanism of action
PepT1 (SLC15A1) oligopeptide transport → intracellular NF-κB / MAPK suppression
PepT1, a proton-coupled di/tripeptide transporter normally confined to small intestinal enterocytes, is markedly upregulated in colonic epithelium and immune cells during active IBD. KPV is recognized as a PepT1 substrate and transported intracellularly. Once inside, at nanomolar concentrations, KPV inhibits nuclear translocation of NF-κB (p65 subunit) and suppresses MAP kinase activation, reducing downstream transcription of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6). The transporter-dependency is strict: KPV prevents tumorigenesis in PepT1-expressing mice but has no effect in PepT1-knockout mice (Laroui 2016). Human intestinal cell-line data (Caco2-BBE, HT29-Cl.19A, Jurkat) supports the intracellular mechanism but is not a human trial.
Non-melanocortin-receptor anti-inflammatory signaling
The anti-inflammatory effect of KPV is NOT blocked by the MC3/4-R antagonist SHU9119 and is preserved in MC1-R-deficient mice (Bhardwaj 2003), distinguishing it definitively from α-MSH and melanocortin agonists like Melanotan II. The downstream anti-inflammatory signaling pathway in non-PepT1-expressing tissues is less well-characterized. The D-Pro diastereomer (Lys-D-Pro-Val) — which can form as a synthesis impurity — has been shown to antagonize IL-1β at the receptor level in alveolar epithelium; whether this mechanism is relevant to L-KPV itself is unclear.
Nitric oxide–mediated corneal epithelial re-epithelialization
Topical KPV accelerated corneal re-epithelialization in rabbits (100% at 60 hours vs 0% in vehicle controls at 1–10 mg/mL, 4×/day). Pre-treatment with the NO-synthase inhibitor L-NAME substantially inhibited the wound-healing facilitation, implicating a NO-mediated component. Human keratinocyte cell-line work shows similar anti-inflammatory signaling but does not establish a wound-healing endpoint.
All mechanistic evidence is from rodent in vivo models, rabbit corneal models, and transformed or primary human cell lines. PepT1 expression in human colonic tissue during IBD is documented, which makes the mechanistic pathway biologically plausible in humans — but plausibility is not efficacy. The estimated ~25–35 min serum half-life derives from rodent data and has not been measured in humans. Oral bioavailability across the full human GI tract, systemic distribution, and tissue penetration are all unknown. Critical nuance for oral dosing: PepT1 upregulation is an IBD-specific phenomenon in the colon, so oral KPV may not be meaningfully absorbed or locally effective in individuals without active intestinal disease.
Key studies
PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation (2008)
Dalmasso G, Nguyen HTT, Yan Y, Laroui H, Charania MA, Ayyadurai S, Sitaraman SV, Merlin D · Gastroenterology 134(1):166–178
- Participants
- No humans. DSS-colitis and TNBS-colitis mouse models; in vitro human intestinal epithelial cell lines (Caco2-BBE, HT29-Cl.19A) and Jurkat T-cells.
- Methodology
- Animal intervention (oral KPV in drinking water) plus in vitro mechanistic assays (NF-κB luciferase reporter, Western blot, ELISA, radiolabeled KPV uptake experiments).
- Result
- Nanomolar KPV inhibited NF-κB and MAPK activation in human intestinal cells. Oral administration reduced DSS- and TNBS-colitis severity (~50% reduction in myeloperoxidase activity; decreased pro-inflammatory cytokines). PepT1 identified as the mediating transporter.
Honest read
Foundational mechanistic paper, well-designed for preclinical work. All therapeutic claims rest on mouse colitis models. DSS and TNBS models capture acute mucosal inflammation but are imperfect surrogates for human chronic IBD. No human pharmacokinetics. No replication by an independent lab has been identified. The Merlin lab at Georgia State is responsible for essentially all KPV intestinal research to date, creating a single-group-dominance concern that is partially offset only by the Catania lab's parallel α-MSH-fragment signaling line.
Dissection of the anti-inflammatory effect of the core and C-terminal (KPV) alpha-melanocyte-stimulating hormone peptides (2003)
Bhardwaj RS, Schwarz A, Becher E, Mahnke K, Schwarz T, Luger TA · J Pharmacol Exp Ther 307(1):197–204
- Participants
- No humans. Crystal-induced peritonitis mouse model; in vitro macrophage studies.
- Methodology
- In vivo peritonitis model with leukocyte migration readout; in vitro macrophage cytokine release; pharmacological receptor blocking (MC3/4-R antagonist SHU9119) plus MC1-R-deficient mouse experiments.
- Result
- KPV exhibited anti-inflammatory and anti-migratory effects that were NOT blocked by SHU9119 and were preserved in MC1-R-deficient mice. KPV mechanism is definitively not melanocortin-receptor mediated.
Honest read
Critical differentiation study. Relatively small animal experiment. Importantly establishes that KPV ≠ melanocortin agonist, which has real-world significance for safety — no tanning, no appetite effects, no MC4-R-mediated sexual-arousal effects. The flip side is that the non-MCR anti-inflammatory pathway is less well-characterized than α-MSH's canonical signaling. Luger group (Münster) — different from the Merlin/Catania anchor labs, which modestly strengthens the multi-group picture for the non-MCR mechanism specifically.
Orally targeted delivery of tripeptide KPV via hyaluronic acid-functionalized nanoparticles efficiently alleviates ulcerative colitis (2017)
Laroui H, Geem D, Xiao B, Viennois E, Gwon L, Dalmasso G, Merlin D, et al. · Molecular Therapy 25(1):69–80
- Participants
- No humans. DSS-induced ulcerative colitis mouse model.
- Methodology
- Nanoparticle engineering (HA-functionalized, KPV-loaded) plus in vivo mouse colitis intervention plus in vitro validation.
- Result
- HA-KPV nanoparticles achieved similar anti-colitis efficacy as free KPV at a 12,000× lower concentration, with dual action: mucosal healing acceleration and inflammation reduction.
Honest read
Elegantly designed proof-of-concept for targeted delivery, not clinical evidence. All data in mice. Nanoparticle formulations face significant translation hurdles — GI stability, manufacturing scalability, immunogenicity, reproducible loading. Merlin lab, consistent with the single-group pattern across the KPV intestinal-research line.
Critical role of PepT1 in promoting colitis-associated cancer and therapeutic benefits of the anti-inflammatory PepT1-mediated tripeptide KPV in a murine model (2016)
Laroui H, Viennois E, Xiao B, Canup BSB, Geem D, Bhatt M, Merlin D · Cell Mol Gastroenterol Hepatol 2(3):340–357
- Participants
- No humans. PepT1-transgenic, PepT1-knockout, and wild-type mice; AOM/DSS colitis-associated cancer model. Analysis of human colonic biopsy specimens (PepT1 expression only, not KPV treatment).
- Methodology
- Genetic mouse models plus pharmacological KPV intervention in the AOM/DSS CAC murine model; immunohistochemistry of human biopsy specimens.
- Result
- PepT1 overexpression promoted colitis-associated cancer; KPV prevented tumorigenesis in WT mice via PepT1 but had no effect in PepT1-KO mice, confirming transporter dependency. Human biopsy data showed elevated PepT1 in colorectal cancer specimens.
Honest read
The human biopsy data is PepT1-expression analysis only — it does NOT measure any KPV effect in humans. The cancer-prevention data is entirely from a chemically induced murine CAC model. Should not be extrapolated as evidence that KPV prevents cancer in humans. Merlin lab again.
Effects of the COOH-terminal tripeptide alpha-MSH(11-13) on corneal epithelial wound healing: role of nitric oxide (2006)
Gabison EE, Huet E, Baudouin C, Menashi S, Nicoletti A, Behar-Cohen F, Brignole-Baudouin F · Experimental Eye Research 83(5):1062–1069
- Participants
- No humans. New Zealand white rabbits (n=8 per group in the main experiment).
- Methodology
- Bilateral mechanical corneal epithelial debridement; topical KPV (1, 5, 10 mg/mL, 4×/day); fluorescein photography every 12 hours; L-NAME pharmacological inhibition of NO synthase; in vitro rabbit corneal epithelial cell viability assay.
- Result
- 100% of KPV-treated corneas fully re-epithelialized by 60 hours vs 0% of vehicle controls (P<0.05). Effect substantially inhibited by L-NAME. In vitro cell viability stimulated at 1–10 µM concentrations.
Honest read
Clean, well-controlled small-animal study. n=8 is adequate for an ocular pharmacology animal study; the effect size is large and reproducible within the paper. However, rabbit cornea is a specific wound-healing model — it is not a surrogate for human skin or gut wounds. The NO mechanism is proposed but not fully characterized. Single paper; no replication identified. Different group from the Merlin/Catania anchors (Gabison et al., Paris / Créteil) — one of the few KPV papers from a third research cluster.
alpha-Melanocyte-stimulating hormone, MSH 11-13 KPV and adrenocorticotropic hormone signalling in human keratinocyte cells (2004)
Capsoni F, Ongari AM, Colombo G, Turcatti F, Catania A · J Investig Dermatol 123(3):562–567
- Participants
- No human subjects. Primary human keratinocyte cultures and keratinocyte cell lines.
- Methodology
- In vitro human keratinocyte cells stimulated with IL-1β or TNF-α; KPV NF-κB inhibition measured; receptor characterization.
- Result
- α-MSH and KPV attenuated inflammatory signaling in human keratinocytes; KPV did not signal through classical melanocortin receptors in these cells.
Honest read
Uses human-derived cells — more translatable than rodent models, but still not a clinical trial. Primary human keratinocyte cultures have known limitations for replicating in vivo skin physiology. Catania lab (Milan), which is the other major single-group contributor to KPV research alongside Merlin. No commercial affiliations identified in search results, though this should be independently verified before any definitive COI statement.
Research timeline
- 1993
Early 1990s — C-terminal tripeptide KPV identified from structure-activity dissection of α-MSH as the minimal sequence retaining anti-inflammatory activity. Initial work uses keratinocyte and macrophage cell lines from the Luger group (Münster) and the Catania group (Milan).
- 2001
Catania et al. show that the D-Pro diastereomer Lys-D-Pro-Val antagonizes IL-1β signaling at the receptor level in alveolar epithelium. Establishes that KPV-related tripeptides can act through IL-1R-level antagonism in addition to the α-MSH pathway — and that synthesis-impurity D-Pro material has distinct biology.
- 2003
Bhardwaj et al. demonstrate that KPV anti-inflammatory activity is NOT mediated by MC1-R, MC3-R, or MC4-R in a crystal-induced peritonitis mouse model — using MC3/4-R antagonist SHU9119 blockade plus MC1-R-deficient mice. Critical mechanistic differentiation from full α-MSH and from melanocortin-receptor agonists like Melanotan.
- 2004
Capsoni et al. (Catania lab) characterize α-MSH, KPV, and ACTH signaling in primary human keratinocyte cell cultures — one of the few KPV publications using human-derived cells directly, though still not a clinical trial.
- 2006
Gabison et al. demonstrate topical KPV accelerates corneal epithelial wound healing in rabbits via a NO-mediated pathway (100% re-epithelialization at 60 hours vs 0% vehicle).
- 2008
Dalmasso et al. (Merlin lab, Georgia State) identify PepT1 as the primary transporter mediating KPV anti-inflammatory effect in intestinal epithelium. Published in Gastroenterology; the foundational paper for the PepT1/NF-κB mechanistic line.
- 2008
Catania lab publishes major Endocrine Reviews synthesis of α-MSH and related tripeptide anti-inflammatory literature; Brzoska et al. publish a parallel review in British Journal of Pharmacology from the Luger group. Establishes the α-MSH-fragment anti-inflammatory class as a published review topic across multiple groups — not independent replication of the KPV-specific therapeutic data, but broader recognition of the class mechanism.
- 2016
Laroui et al. (Merlin lab) demonstrate KPV suppresses colitis-associated carcinogenesis in an AOM/DSS murine model — strictly PepT1-dependent (no effect in PepT1-knockout mice). Human biopsy data in the same paper is PepT1-expression analysis only.
- 2017
Laroui et al. (Merlin lab) publish hyaluronic-acid-functionalized nanoparticle delivery system for oral KPV in DSS colitis — achieves equivalent efficacy at 12,000× lower concentration vs free peptide. Proof-of-concept for targeted delivery; not a human trial.
- 2025
Ghazvini et al. systematic review in JGH Open includes KPV among preclinical-only anti-inflammatory peptide candidates for IBD. Confirms absence of completed human trials as of 2025.
- 2026
April 15, 2026 — FDA publishes 503A Categories Update for April 2026, removing 12 peptide substances from Category 2 effective April 22, 2026; KPV reportedly included. Removal is attributed to nominator withdrawal, NOT safety clearance or approval. April 16, 2026 Federal Register notice (2026-07361) formally schedules KPV for PCAC review July 23–24, 2026. Docket FDA-2025-N-6895; public comment closes July 22, 2026.
What we don't know
- Human efficacy for any indication. No completed human clinical trials for IBD, wound healing, skin inflammation, or anything else. All therapeutic claims rest on preclinical data.
- Human pharmacokinetics. Oral bioavailability in humans is unknown. The fraction of orally administered KPV that reaches intestinal tissue — and how that fraction depends on PepT1 expression, disease state, and individual variation — is unmeasured.
- Systemic distribution and half-life in humans. The ~25–35 min serum half-life is estimated from rodent data and has not been confirmed in humans.
- Long-term safety in humans. No chronic administration safety data in any human population. Theoretical concerns include sustained NF-κB suppression.
- Optimal dose, route, and schedule for any human indication. Animal mg/kg doses have not been formally translated to human-equivalent doses with validated pharmacokinetic support.
- Drug interactions — notably with corticosteroids, biologics used in IBD (anti-TNF, anti-integrin, anti-IL-12/23), and any oral drug that depends on PepT1 transport for absorption.
- Whether PepT1 dependency limits oral efficacy in healthy colons. PepT1 colonic upregulation is an IBD-specific phenomenon; in individuals without active intestinal disease, orally administered KPV may not be meaningfully absorbed or locally effective.
- Subcutaneous vs oral efficacy in humans. Most animal models used oral or intraperitoneal administration. Whether SC dosing — common in real-world compounding use — achieves therapeutic tissue concentrations is unstudied.
- Cancer safety in the general population. NF-κB has complex tumor-suppressor and tumor-promoter roles depending on cancer type and context. One mouse study showed anti-tumor activity in colitis-associated cancer; broader oncological safety has not been studied.
- Pregnancy, lactation, and pediatric safety. No data.
- Whether the free acid (H-KPV-OH, ~342 Da), acetate salt, and amidated form (Ac-KPV-NH2, ~383 Da) are bioequivalent. These are distinct chemical entities with potentially different stability, absorption, and potency profiles. No comparative data exists.
- Independent replication of the PepT1/colitis line outside the Merlin lab, or of the α-MSH-fragment signaling line outside the Catania lab.
Regulatory status
| Jurisdiction | Status | Details | Last Verified | Source |
|---|---|---|---|---|
| United States (FDA) | 503A Category 3 | No FDA approval for any indication. Regulatory status is in transition as of April 22, 2026: KPV was previously listed on Category 2 of the interim 503A bulk drug substances list (the "significant safety risks" category — effectively prohibiting compounding). On April 15, 2026, the FDA published a 503A Categories Update removing 12 peptide substances from Category 2 effective April 22, 2026; secondary sources indicate KPV is among them, though the primary FDA PDF was not directly accessible during research. Removal via nominator withdrawal is NOT a safety determination and does NOT place KPV on Category 1 (the positive compounding list). The FDA Pharmacy Compounding Advisory Committee is scheduled to formally review KPV (free base) and KPV acetate on July 23–24, 2026 (docket FDA-2025-N-6895; public comment closes July 22, 2026) — this meeting will decide on potential 503A Bulks List inclusion. Until the PCAC recommendation is issued and FDA acts on it, KPV is NOT on the 503A positive list and cannot be legally compounded under 503A. "Sold for research purposes only" is a legal category allowing sale but not authorizing human administration. | 2026-04-22 | |
| Canada (Health Canada) | Not Authorized | No Drug Identification Number (DIN) has been issued; KPV is not listed as a Natural Health Product with the Natural and Non-prescription Health Products Directorate. As a synthetic peptide it would not qualify as an NHP. Licensed compounding pharmacies may prepare KPV for specific patient needs under the compounding framework in Section C.01.040 of the Food and Drug Regulations, subject to professional judgment. Health Canada has issued general advisories warning against injectable peptides bought online; no KPV-specific regulatory document was located during research. | 2026-04-22 | |
| United Kingdom (MHRA) | Not Authorized | No MHRA marketing authorization; KPV is not listed as a licensed medicine. Licensed specials manufacturers may prepare KPV under the Medicines Act 1968 Section 10 exemption for "specials" on a named-patient basis. No primary MHRA document specifically addressing KPV was located during research. | 2026-04-22 | |
| European Union (EMA) | Not Authorized | No EU central marketing authorization; KPV does not appear in the EMA's European Public Assessment Reports. Compounding regulation for unauthorized substances varies by member state. No primary EMA document specifically addressing KPV was located during research. | 2026-04-22 | |
| Australia (TGA) | Not Authorized | KPV is not registered on the Australian Register of Therapeutic Goods (ARTG). The TGA has issued broad guidance on unapproved peptide products but no KPV-specific enforcement action was located. Licensed compounding pharmacies may prepare KPV for specific patients under the TGA's human-use exemptions, subject to TGA guidance; import and supply without authorization may constitute an offence. | 2026-04-22 | |
| WADA | Not listed | KPV is NOT explicitly named on the 2026 WADA Prohibited List. The S2 category (Peptide Hormones, Growth Factors, Related Substances and Mimetics) includes a catch-all for substances with "similar chemical structure or similar biological effects" to prohibited peptide hormones. KPV is a fragment of α-MSH — but does NOT activate melanocortin receptors and has no documented performance-enhancing effect, which reduces (though does not eliminate) the catch-all risk. Practical assessment: KPV is unlikely to be detected on standard doping control panels and is not known to confer performance advantage. Athletes in WADA-governed sports should obtain written guidance from WADA or their national anti-doping organization before any use. | 2026-04-22 |
Safety profile
Reported side effects
- No systematically collected human adverse-event data exists — no published human trials.
- In published mouse and rabbit studies, KPV was well-tolerated with no dose-limiting toxicity, organ pathology, or behavioral changes at the doses studied.
- Longest published continuous administration was approximately 12 weeks in murine colitis models; no cumulative toxicity reported — but mouse-scale exposure is not a substitute for human safety data.
- No melanocortin-receptor-mediated effects expected (no tanning, no MC4-R sexual arousal, no appetite dysregulation) — a meaningful safety differentiation from Melanotan I/II.
Theoretical concerns
Chronic NF-κB suppression
KPV's core mechanism involves suppression of NF-κB, a master regulator of innate immunity. Chronic systemic NF-κB suppression could theoretically impair host defense against infection or blunt surveillance of early neoplastic cells. The concern is theoretical and has not been studied for KPV specifically.
Severity: theoretical
PepT1-mediated competition with dietary peptides or orally administered drugs
KPV is a PepT1 substrate. If KPV competes meaningfully with dietary di/tripeptides or orally administered PepT1-dependent drugs (e.g., β-lactam antibiotics, valacyclovir) for transport, it could theoretically affect absorption of co-administered compounds. Not studied for KPV.
Severity: theoretical
D-Pro epimerization products during synthesis
The proline at position 2 is particularly susceptible to epimerization during Fmoc solid-phase synthesis under basic conditions, generating the D-Pro diastereomer Lys-D-Pro-Val. Lys-D-Pro-Val has been studied independently and has distinct biological properties (IL-1β receptor-level antagonism in alveolar epithelium). Standard reversed-phase HPLC may not resolve the L-Pro and D-Pro diastereomers — chiral HPLC or specific mass-spectrometric fragmentation is required. Biological contribution of D-Pro impurity when present in nominally "KPV" material is unstudied.
Severity: possible
Ac-KPV-NH2 vs H-KPV-OH identity confusion
Some vendors sell the N-acetylated, C-amidated form (Ac-KPV-NH2, ~383 Da) under the same 'KPV' label as the free acid (H-KPV-OH, ~342 Da). These are structurally distinct compounds with different charge states, different HPLC behavior, and no published bioequivalence data. Preclinical studies have used one form or the other without always making this explicit. Buyers cannot distinguish without mass-spectrometry confirmation on the COA.
Severity: possible
Contraindications
- Pregnancy and lactation (no safety data in any species)
- Active malignancy (theoretical — NF-κB has complex tumor-suppressor and tumor-promoter roles depending on context)
- Immunocompromised status (theoretical — chronic NF-κB suppression could further impair host defense)
- Solid-organ transplant recipients on immunosuppressive therapy (theoretical additive immunosuppression)
- Known hypersensitivity to KPV or any excipient in a specific compounded preparation
- Due to complete absence of human safety data, all populations should be considered contraindicated for clinical use outside formal research settings.
Interactions
- No published drug-interaction data in humans.
- Theoretical PepT1-transport competition with β-lactam antibiotics, valacyclovir, and other PepT1-dependent oral drugs (absorption effect, direction unclear)
- Anti-TNF biologics, anti-integrin agents, and other IBD immunomodulators — combined NF-κB-axis suppression has not been studied
- Corticosteroids — additive immunosuppression is theoretically possible; no data
- NSAIDs — no formal interaction data; concomitant use in real-world compounding scenarios is untested
Dosing observed in the literature
No human dosing data exists in published studies for any route or indication. All doses listed above are animal experimental doses. Application of animal mg/kg doses to humans using standard allometric scaling would yield rough estimates only and has not been validated for KPV pharmacokinetics or pharmacodynamics. KPV is not approved for human use in any jurisdiction covered in this profile. Content is for research reference only and is not medical advice.
| Route | Range | Context | Source |
|---|---|---|---|
| oral | ~1–10 mg/kg/day (estimated from water-intake conventions) | DSS and TNBS colitis mouse models; KPV administered in drinking water. Dose estimate from standard water-intake calculations. | PMID:18061177 |
| oral | Equivalent of ~0.5 mg/kg (HA-nanoparticle formulation) | DSS ulcerative colitis mouse model; nanoparticle achieves similar efficacy at 12,000× lower dose than free peptide. | PMID:28143741 |
| intraperitoneal | 100–300 µg per mouse (~5–15 mg/kg) | Crystal-induced peritonitis and systemic inflammation mouse models. | PMID:12750433 |
| topical | 1, 5, 10 mg/mL; 30 µL drops; 4× per day × 4 days | Rabbit corneal epithelial wound-healing model. | PMID:16965771 |
Stability & handling
- Lyophilized shelf life
- 2–3 years at −20°C is typical for small tripeptides under proper storage (standard peptide-handling guidance; no peer-reviewed KPV-specific stability study identified).
- Lyophilized storage
- Freeze at −20°C (long-term) or 2–8°C (short-term). Protect from moisture and light. Equilibrate sealed vials to room temperature before opening to avoid moisture condensation on the powder.
- Reconstitution diluents
- Bacteriostatic water for injection (0.9% benzyl alcohol in sterile water) — standard for multi-dose research vials, Sterile water for injection (single-use only), Phosphate-buffered saline (PBS) — for in vitro research applications
- Reconstituted (refrigerated)
- Research-market convention of ~28–30 days at 2–8°C with bacteriostatic water (benzyl alcohol provides antimicrobial protection). No peer-reviewed KPV-specific stability study.
- Reconstituted (room temp)
- Degradation accelerates above 8°C; use promptly if not refrigerated. No formal KPV-specific room-temperature stability data.
- OK to refreeze
- No
- Light sensitive
- Yes — protect from light
KPV's small size (3 amino acids) makes it generally more stable than larger peptides, but it has several compound-specific failure modes that matter for what is actually in the vial and should be reflected on the COA. (1) FREE ACID vs ACETATE SALT — KPV sold as 'KPV acetate' has higher MW than the free acid (+~60 Da per acetate counterion). A COA reporting '≥98% purity by HPLC' without specifying the form allows meaningful dosing ambiguity; the FDA is evaluating KPV free base and KPV acetate as distinct substances for good reason. Red flag: no salt-form declaration on the COA. (2) Ac-KPV-NH2 vs H-KPV-OH — the N-acetylated, C-amidated form (~383 Da) is a structurally different compound than the free acid (~342 Da). Some vendors sell it as 'KPV' without disclosure. Red flag: product labeled simply 'KPV' without N-terminal and C-terminal modifications explicitly stated; the label should match the research application. (3) PROLINE EPIMERIZATION (D-Pro impurity) — Pro at position 2 is susceptible to epimerization during Fmoc synthesis under basic conditions, generating Lys-D-Pro-Val with distinct biology. Standard reversed-phase HPLC may not resolve L-Pro and D-Pro diastereomers. Red flag: no chiral analysis or explicit L-Pro configuration confirmation. (4) DELETION SEQUENCES (KP or PV dipeptide) — in tripeptide synthesis, failure to add the first or last amino acid generates dipeptide deletion products that can partially co-elute with KPV on standard HPLC, artificially inflating apparent purity. Red flag: no mass-spectrometry confirmation (ESI-MS or MALDI) of the correct 342-Da mass. (5) TFA RESIDUAL — trifluoroacetic acid used in Fmoc deprotection and preparative HPLC can remain as a counterion. At 5 mg vial sizes, a 5% TFA contamination is 0.25 mg TFA — relevant for inflammatory cell-culture work and sensitive assays. Red flag: no residual-solvent panel, no statement of counterion type.
Frequently asked questions
Does KPV treat Crohn's disease or ulcerative colitis?
Not proven in humans. Mouse models of chemically induced colitis (DSS, TNBS) show significant anti-inflammatory effects — but those are animal models, not human trials. Human IBD involves complex immune dysregulation that mouse DSS colitis only partially captures, and no completed human clinical trial for KPV in IBD has been published. Until a human trial is completed, KPV should not be used as a replacement for evidence-based IBD therapy.
Is KPV the same thing as Melanotan?
No — and this is the single most important distinction for KPV. α-MSH is the 13-amino-acid parent peptide; KPV is just its last three amino acids. α-MSH activates MC1-R (pigmentation), MC3-R, and MC4-R, producing broad hormonal effects. KPV does NOT activate any of these melanocortin receptors at pharmacological concentrations — its anti-inflammatory effect works via PepT1-mediated NF-κB inhibition, an entirely different pathway. Melanotan II is a synthetic non-selective MCR agonist causing intense tanning, sexual arousal via MC4-R in the CNS, and frequent nausea — KPV has none of those effects. Conflating KPV with Melanotan is a common online error and reflects unfamiliarity with melanocortin pharmacology.
Is KPV safe?
The honest answer is: we don't know for humans. No published human safety studies exist. In animal models, KPV appears well-tolerated at the doses studied. It does not activate melanocortin receptors, which removes several mechanism-based safety concerns associated with full α-MSH and with Melanotan analogs. The endogenous-peptide-fragment argument ('it's a fragment of a natural hormone') is a reasonable biological inference but not a substitute for clinical safety data. Theoretical concerns include chronic NF-κB suppression with long-term use.
Can KPV be legally prescribed or compounded?
In the US, as of April 22, 2026, KPV is not on the FDA 503A positive list and therefore cannot be legally compounded under standard 503A rules. The July 23–24, 2026 PCAC meeting (docket FDA-2025-N-6895) will formally evaluate KPV (free base and acetate) for inclusion. In other jurisdictions, compounding regulations vary — KPV may be compounded by licensed pharmacies on a named-patient basis in some countries. 'Sold for research purposes only' in the US is a legal category that allows sale but does not authorize human administration.
Does KPV cause tanning or pigmentation?
No, based on mechanism. KPV does not activate MC1-R, the melanocortin receptor responsible for melanogenesis. This has been demonstrated directly in MC1-R-deficient mice (where the anti-inflammatory effect was preserved) and via MC3/4-R antagonist blockade (which also did not block the effect). Unlike Melanotan I/II — which are potent MC1-R agonists — KPV should not cause tanning. This is a real, meaningful differentiator, not a marketing talking point.
Is KPV on the WADA Prohibited List?
Not by name. The WADA 2026 S2 category includes a catch-all for substances with 'similar chemical structure or similar biological effects' to prohibited peptide hormones. KPV is a fragment of α-MSH, and some α-MSH analogs with potent MCR agonism have been associated with doping concerns — but KPV does not activate melanocortin receptors and has no documented performance-enhancing effect. Practical doping risk appears low, but athletes subject to WADA testing should obtain written guidance from their national anti-doping organization before any use.
What should I look for on a KPV COA?
Five items, separately reported: (1) MASS SPECTROMETRY confirmation of the correct molecular mass (342 Da for H-KPV-OH free acid; 383 Da for Ac-KPV-NH2 amidated form) — and an explicit statement of WHICH FORM the product is. Some vendors sell Ac-KPV-NH2 under the same 'KPV' label; the two are structurally different compounds. (2) SALT FORM DECLARATION — free acid vs acetate salt vs TFA counterion. The FDA evaluates 'KPV free base' and 'KPV acetate' as distinct substances for good reason. (3) CHIRAL ANALYSIS or explicit L-Pro configuration confirmation — reverse-phase HPLC does not detect D-Pro epimerization impurity (Lys-D-Pro-Val), which has distinct biology. (4) HPLC PURITY plus a check for deletion-sequence dipeptides (KP or PV) that can partially co-elute with KPV and artificially inflate apparent purity — mass spec confirms correct molecular mass. (5) RESIDUAL TFA panel and statement of counterion type, particularly relevant at small vial sizes where percentage TFA contamination matters for inflammatory assays. A COA showing only '≥98% purity by HPLC' without these five items has not characterized what is actually in the vial.
Should I take KPV for gut health or inflammation?
ClearBatch does not provide medical advice. What the evidence supports saying is: there is no published human trial showing KPV is effective for gut health or inflammation in people. There is meaningful preclinical evidence in mouse colitis models, concentrated in one research group (Merlin lab at Georgia State), without independent replication of the headline therapeutic findings. This gap between animal data and human use is common in early-stage research but is important context before any health decision. Individuals considering KPV should discuss with a qualified physician who can assess their specific situation, condition, and risk tolerance.
Last researched: Apr 22, 2026
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