KPV Signal Filter Research

Research dossier

KPV Evidence Profile

Last Updated: July 2026

KPV is the Lys–Pro–Val sequence corresponding to residues 11 through 13 at the C-terminal end of α-MSH. Cell and animal studies have examined materials described as KPV or KPV derivatives in PepT1 uptake and inflammatory-signaling experiments, including NF-κB and MAPK readouts.3, 7, 10, 14 FDA's May 2026 staff review did not identify information on KPV free base or KPV acetate administered to humans, or clinical efficacy, pharmacokinetic, pharmacodynamic, or safety data for those reviewed forms.16

Research overview

What researchers have studied

KPV research began with the C-terminal fragment of α-MSH and later expanded into questions of cellular uptake and inflammatory signaling. PepT1-mediated uptake has been reported in selected intestinal and immune-cell models. Under defined stimulation, some studies also reported lower NF-κB or MAPK activity and changes in cytokine, chemokine, nitric oxide, or oxidative-stress readouts.3, 7, 10, 14

Animal work includes mouse models of intestinal inflammation and a rabbit corneal-abrasion model. Other studies examined delivery through nanoparticles, hydrogels, iontophoresis, microneedles, or engineered conjugates. Each result belongs to the material, formulation, route, species, and endpoint described in the experiment.6, 7, 8, 9, 11, 12, 13, 15

FDA's May 2026 staff review did not identify information on KPV free base or KPV acetate administered to humans. The available research therefore describes preclinical mechanisms and model-specific outcomes while human exposure, safety, and clinical effects remain uncharacterized.16

α-MSH terminal sequence13 residues total
Distinct materials in KPV research and regulation
KPV free baseKPV acetate saltTerminally modified materialLabeled, dimeric, or conjugated derivative
K, P, and V denote lysine, proline, and valine. Materials retaining this sequence can differ in terminal groups, counterions, tags, dimerization, or delivery scaffolds, so each finding should follow the material description reported by its source.16

Five-phase research map

How KPV moves through the evidence

The sequence begins with chemical identity, follows PepT1-mediated uptake and signaling observations, then moves through preclinical models and the current human-evidence gap. The signal-filter motif visualizes the direction of reported laboratory changes under defined experimental conditions.

Phase 01 / 05

Molecular identity

KPV within the α-MSH sequence

KPV consists of lysine, proline, and valine, corresponding to residues 11 through 13 at the C-terminal end of α-MSH.7, 16

Key interpretation

The literature includes materials described as KPV or α-MSH(11–13), along with labeled and engineered derivatives. FDA separately evaluated KPV free base and KPV acetate while noting that many reports did not make that distinction clear.1, 7, 10, 13, 15, 16

Phase 02 / 05

Cellular uptake

PepT1-mediated cellular uptake

Experiments in Caco2-BBE and HT29-Cl.19A intestinal epithelial cells and Jurkat T cells found PepT1-mediated uptake of material described as KPV.7

Key interpretation

PepT1 is a proton-coupled transporter for dipeptides and tripeptides. The downstream molecular target associated with the reported signaling effects remains unknown.7, 16

Phase 03 / 05

Intracellular observations

Changes in signaling activity

Stimulated intestinal epithelial and immune-cell models reported lower NF-κB or MAPK readouts after KPV exposure.7, 14 In the immortalized human bronchial epithelial cell line 16HBE14o-, Land reported reduced NF-κB reporter activity and reduced nuclear translocation of p65/RelA.10

Key interpretation

These findings describe cellular responses under specific experimental conditions, while the complete molecular mechanism and effects in humans remain uncharacterized.7, 10, 14, 16

Pro-inflammatory stimulus TNF-α, IL-1β, or another model-specific trigger
Observed modifier Following KPV exposure Lower pathway activity was observed in selected cell models Final molecular target unresolved

NF-κB pathway

From the pro-inflammatory stimulus

Reduced p65/RelA nuclear translocation Reported in 16HBE14o- cells10
Cytoplasm
Reduced entry
Nucleus
Lower NF-κB reporter activityMeasured with a reporter assay10

MAPK pathway

From the pro-inflammatory stimulus

Lower activation of selected MAPK readoutsCaco2-BBE and HaCaT cell models7, 14
Cross-study schematic combining observations from distinct cell models; triggers and readouts varied by experiment.7, 10, 14

Phase 04 / 05

Animal and delivery research

Findings across preclinical models

Mouse intestinal models and a rabbit corneal-abrasion model reported changes in selected tissue measures.6, 7, 8, 11

Key interpretation

Nanoparticles, hydrogels, microneedles, iontophoresis, and engineered conjugates were studied as distinct formulations and routes. Their findings apply to the test system described in each report.9, 12, 13, 15

Phase 05 / 05

Evidence maturity

Human evidence remains uncharacterized

FDA's May 2026 staff review did not identify information on KPV free base or KPV acetate administered to humans, or clinical efficacy, pharmacokinetic, pharmacodynamic, or safety data for those reviewed forms.16

Key interpretation

Human exposure, route-specific behavior, and adverse-effect profiles remain uncharacterized. Human-derived cells and cadaver skin provide laboratory information without measuring clinical outcomes.13, 16

Interpreting the evidence

Keeping the material, route, and model connected

KPV research covers chemically and biologically distinct test systems. FDA treats KPV free base and KPV acetate as distinct bulk substances, while terminally modified materials and engineered conjugates introduce further differences. Results from nanoparticles, hydrogels, microneedles, or iontophoresis remain specific to those formulations and routes.9, 12, 13, 15, 16

PepT1 mediated cellular uptake in selected intestinal and immune-cell experiments. Researchers have not yet identified the downstream molecular target associated with the reported signaling changes. NF-κB, MAPK, cytokines, chemokines, and tissue histology capture different parts of the response and depend on the experimental model.3, 7, 10, 14, 16

The safety record is incomplete. FDA did not identify human exposure or clinical-safety studies and noted gaps in standard nonclinical toxicology, including acute, repeat-dose, genotoxicity, reproductive, developmental, and carcinogenicity testing for KPV free base and KPV acetate. The absence of adverse-event reports is difficult to interpret when human exposure has not been established.16

Research map

How KPV has been studied

Each row shows the question researchers asked, the laboratory or animal setup they used, the result they reported, and the limits of that result.

KPV research questions, study setups, reported results, and limits
Research question Study setup Reported result Limits
How did KPV enter the cells? Lab-grown intestinal and immune cells from established human cell lines Material described as KPV entered these cells through PepT1, a transporter that carries small peptides across the cell membrane.7 The experiments measured uptake in cell cultures. They did not track where KPV travels in the human body or identify the molecule it acts on after entering a cell.
Which cell signals changed after KPV exposure? Lab-grown cells from the intestine, immune system, airways, and skin Some studies reported lower activity in NF-κB and MAPK, two systems cells use when responding to inflammation or stress. Other experiments measured inflammatory signals and the movement of p65/RelA into the nucleus.3, 7, 10, 14 The studies used different cell types, inflammatory triggers, KPV concentrations, and measurements, so their results describe several separate experiments.
Has KPV's cellular target been identified? Receptor and cAMP experiments in murine macrophages and a peritonitis model, together with DSS colitis in mice carrying a nonfunctional MC1 receptor KPV did not increase cAMP in the tested macrophage model, and its reported effects were not fully accounted for by a single classical melanocortin-receptor pathway.3, 4, 8 These experiments did not identify the downstream molecular target or rule out every possible receptor contribution.
What happened in mouse intestinal studies? Mice with laboratory-induced intestinal inflammation, including models of colitis and inflammation-linked colon cancer Some studies reported less inflammation, less tissue damage, or fewer tumor-related changes.7, 8, 11 These results came from laboratory mouse models. KPV has not been tested as a treatment for inflammatory bowel disease or cancer in people.
What happened in the rabbit eye study? Rabbits with a small abrasion on the cornea, the clear surface at the front of the eye The surface injury closed faster after topical material described as α-MSH(11–13), and nitric oxide measurements changed.6 The study examined surface healing in rabbit eyes. It provides no evidence about other wounds or healing in people.
Could KPV pass through skin? Sections of donated human skin tested in the laboratory, outside the body Researchers did not detect passive KPV permeation above the assay limit. Microneedles and iontophoresis increased delivery into and across the removed skin.13 The study measured movement through removed skin, without measuring whole-body exposure, benefit, or safety.
Did the delivery method change the result? Cells and mice tested with KPV-loaded nanoparticles, nanoparticle-in-hydrogel systems, or a chemically linked proKPV conjugate Changing how the peptide was packaged affected its delivery or the results measured in the experiment.9, 12, 15 Each finding applies to the specific delivery system used in that study.
What has been measured in people? FDA review of published research and safety information FDA's May 2026 staff review did not identify information on KPV free base or KPV acetate administered to humans, or clinical efficacy, pharmacokinetic, pharmacodynamic, or safety data for those forms.16 Possible benefits and risks in people remain unknown because human administration studies were not identified.

Evidence chronology

How KPV research developed

The literature moved from early fragment studies into cellular signaling, animal models, delivery systems, and a formal regulatory review of the evidence gaps.

  1. Early fragment activity

    The study reported reduced ear swelling from α-MSH(11–13) in a mouse contact-dermatitis model. FDA's 2026 review classifies the material used in this paper as N-acetylated KPV.1, 16

  2. In-vitro antimicrobial observations

    α-MSH fragments including KPV were studied against Staphylococcus aureus and Candida albicans cultures.2

  3. NF-κB and nitric oxide signaling

    RAW 264.7 macrophage-like cells were used to examine α-MSH(11–13) effects on NF-κB DNA binding and nitric oxide production after LPS and interferon-γ stimulation.3

  4. –

    Receptor dependence was tested

    Mouse and human-keratinocyte experiments tested melanocortin-receptor and cAMP involvement, finding that a single classical receptor pathway did not account for all reported KPV responses.4, 5

  5. Rabbit corneal repair model

    A topical rabbit corneal-abrasion study of material described as α-MSH(11–13) reported faster epithelial closure and changes in nitric oxide measures.6

  6. PepT1 and mouse-colitis studies

    Cellular uptake, NF-κB/MAPK readouts, and multiple mouse intestinal-inflammation models expanded the evidence map.7, 8

  7. –

    Delivery and knockout models expanded

    Nanoparticle and hydrogel systems, PepT1-knockout mice, and cadaver-skin experiments separated delivery questions from biological-response questions.9, 11, 12, 13

  8. –

    New models remained preclinical

    A keratinocyte study and experiments with the distinct self-immolative proKPV conjugate added cellular and mouse observations.14, 15

  9. FDA documented the evidence gaps

    FDA staff reported unresolved identity, effectiveness, pharmacology, and safety questions for KPV free base and KPV acetate ahead of advisory-committee review.16, 17

Regulatory snapshot

Regulatory status in July 2026

Recheck after July 24, 2026

United States — PSC review date: July 11, 2026

FDA's May 2026 staff briefing states that KPV free base and KPV acetate are not components of an FDA-approved drug and have no USP or NF drug-substance monograph. Staff proposed that neither substance be added to the section 503A Bulks List. The Pharmacy Compounding Advisory Committee is scheduled to discuss KPV on July 23, 2026. Advisory recommendations are non-binding, and FDA had not issued final agency action as of PSC's review date.16, 17

Canada - Health Canada advisory

Health Canada's April 9, 2026 advisory names KPV among unauthorized injectable peptide drugs seized in Canada. The advisory concerns product authorization and states that unauthorized products have not been assessed for safety, efficacy, or quality. It provides no KPV-specific clinical adverse-event data. Read the advisory 18

Researcher FAQ

Frequently asked questions

What does the name KPV describe?

KPV is the lysine–proline–valine sequence corresponding to residues 11 through 13 at the C-terminal end of α-MSH. KPV free base, KPV acetate, terminally modified material, and engineered derivatives retain different material descriptions because terminal chemistry, counterions, tags, or delivery design can affect how a preparation behaves.7, 16

What role does PepT1 play in KPV research?

PepT1, encoded by SLC15A1, is a proton-coupled transporter for dipeptides and tripeptides. Experiments in selected intestinal epithelial and immune-cell systems found PepT1-mediated KPV uptake. The downstream molecular target associated with the reported signaling effects remains unresolved.7

What have cell studies reported about NF-κB and MAPK?

Several stimulated cell systems reported lower NF-κB or MAPK activity and changes in cytokine, chemokine, oxidative-stress, or nuclear-translocation readouts after KPV exposure. Results depend on the cell type, stimulus, concentration, and endpoint, and no single downstream molecular target has been established.3, 7, 10, 14

What have animal and delivery studies reported?

Mouse intestinal-inflammation models reported changes in inflammatory and histologic measures, while a rabbit corneal-abrasion study reported faster re-epithelialization. Nanoparticles, hydrogels, microneedles, iontophoresis, and engineered conjugates were studied as specific delivery systems, so their results remain attached to those formulations and routes.6, 7, 8, 9, 11, 12, 13, 15

Has KPV been studied in people?

FDA's May 2026 staff review did not identify information on KPV free base or KPV acetate administered to humans, or human efficacy, pharmacokinetic, pharmacodynamic, clinical-safety, or other exposure data for those forms. Work in human-derived cells and cadaver skin provides laboratory information on cellular behavior and delivery without measuring whole-body exposure or clinical outcomes.16

What is known about KPV safety?

Human safety remains uncharacterized. FDA did not identify human exposure or clinical-safety studies and noted major gaps in acute, repeat-dose, genotoxicity, reproductive, developmental, and carcinogenicity testing for KPV free base and KPV acetate. The absence of adverse-event reports is difficult to interpret when exposure is uncertain.16

Terminology

Glossary of terms

α-MSH

Alpha-melanocyte-stimulating hormone, a 13-residue melanocortin peptide. KPV corresponds to its final three residues.

Chemical form

KPV free base and KPV acetate are distinct bulk substances. Terminally modified, labeled, dimeric, and conjugated materials add further chemical or delivery differences.16

PepT1 / SLC15A1

A proton-coupled transporter that moves many dipeptides and tripeptides across cell membranes. Selected KPV experiments identified PepT1-mediated uptake.7

NF-κB

A family of transcription factors that helps coordinate immune, stress, survival, and inflammatory gene-expression programs.

MAPK

A group of kinase pathways that relay stress, growth, and other signals within cells.

Laboratory models

In-vitro studies use cultured cells or biochemical systems; ex-vivo studies use tissue removed from an organism. Animal models examine selected biological processes in a living nonhuman organism.

PK/PD

Pharmacokinetics describes absorption, distribution, metabolism, and elimination. Pharmacodynamics relates exposure to biological effects.

References & source data

  • 1.Hiltz ME, Lipton JM. (1989). Antiinflammatory activity of a COOH-terminal fragment of the neuropeptide α-MSH. FASEB J. 3(11):2282–2284. PMID 2550304Mouse contact-dermatitis model; ear-swelling endpoint. FDA's 2026 review classifies the material as N-acetylated KPV.
  • 2.Cutuli M, et al. (2000). Antimicrobial effects of α-MSH peptides. J Leukoc Biol. 67(2):233–239. doi:10.1002/jlb.67.2.233α-MSH(11–13)/KPV in S. aureus and C. albicans cultures; exact salt and terminal chemistry were not resolved in the abstract.
  • 3.Mandrika I, et al. (2001). Effects of melanocortin peptides on lipopolysaccharide/interferon-γ-induced NF-κB DNA binding and nitric oxide production in macrophage-like RAW 264.7 cells. Biochem Pharmacol. 61(5):613–621. doi:10.1016/S0006-2952(00)00583-9α-MSH(11–13); RAW 264.7 cells; LPS/interferon-γ stimulus; NF-κB DNA binding, nitrite, and cAMP readouts; exact form unclear.
  • 4.Getting SJ, et al. (2003). Dissection of the anti-inflammatory effect of the core and C-terminal (KPV) α-MSH peptides. J Pharmacol Exp Ther. 306(2):631–637. PMID 12750433α-MSH(11–13)/KPV; mouse peritonitis and receptor/cAMP experiments; exact form unclear.
  • 5.Elliott RJ, et al. (2004). α-melanocyte-stimulating hormone, MSH 11–13 KPV and adrenocorticotropic hormone signalling in human keratinocyte cells. J Invest Dermatol. 122(4):1010–1019. doi:10.1111/j.0022-202X.2004.22404.xHuman keratinocytes and MC1R-transfected CHO cells; cAMP and calcium readouts; terminal and salt form unclear.
  • 6.Bonfiglio V, et al. (2006). Effects of the COOH-terminal tripeptide α-MSH(11–13) on corneal epithelial wound healing: role of nitric oxide. Exp Eye Res. 83(6):1366–1372. doi:10.1016/j.exer.2006.07.014Topical rabbit corneal-abrasion model; epithelial closure and nitric oxide endpoints; exact form unclear.
  • 7.Dalmasso G, et al. (2008). PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation. Gastroenterology. 134(1):166–178. PMCID PMC2431115KPV and radiolabeled KPV; Caco2-BBE, HT29-Cl.19A, Jurkat, DSS, and TNBS models; PepT1, NF-κB/MAPK, IL-8, and histology endpoints; free base versus acetate unclear.
  • 8.Kannengiesser K, et al. (2008). Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease. Inflamm Bowel Dis. 14(3):324–331. doi:10.1002/ibd.20334α-MSH(11–13)/KPV; DSS and transfer-colitis mice, including mice with a nonfunctional MC1 receptor; histology and MPO endpoints; exact form unclear.
  • 9.Laroui H, et al. (2010). Drug-loaded nanoparticles targeted to the colon with polysaccharide hydrogel reduce colitis in a mouse model. Gastroenterology. 138(3):843–853.e1–2. PMID 19909746KPV-loaded nanoparticles within an alginate/chitosan hydrogel; Caco2-BBE cells and DSS mice.
  • 10.Land SC. (2012). Inhibition of cellular and systemic inflammation cues in human bronchial epithelial cells by melanocortin-related peptides. Int J Physiol Pathophysiol Pharmacol. 4(2):59–73. PMCID PMC3403564Custom KPV and tagged H6-KPV in different experiments; 16HBE14o- cells; TNF-α/RSV stimuli; NF-κB reporter, p65/RelA, cytokine, and MMP endpoints; free base versus acetate unclear.
  • 11.Viennois E, et al. (2016). Critical role of PepT1 in promoting colitis-associated cancer and therapeutic benefits of the anti-inflammatory PepT1-mediated tripeptide KPV in a murine model. Cell Mol Gastroenterol Hepatol. 2(3):340–357. PMCID PMC4957955KPV in AOM/DSS and PepT1 wild-type/knockout mice; tumor-burden and inflammatory endpoints; exact form unclear.
  • 12.Xiao B, et al. (2017). Orally targeted delivery of tripeptide KPV via hyaluronic acid-functionalized nanoparticles efficiently alleviates ulcerative colitis. Mol Ther. 25(7):1628–1640. PMCID PMC5498804KPV-loaded hyaluronic-acid-functionalized nanoparticles in a hydrogel; cell and DSS-mouse models; exact KPV form unclear.
  • 13.Pawar K, et al. (2017). Transdermal iontophoretic delivery of Lysine-Proline-Valine (KPV) peptide across microporated human skin. J Pharm Sci. 106(7):1814–1820. PMID 28343991KPV and FITC-labeled KPV in ex-vivo human cadaver skin; passive, microneedle, and iontophoretic delivery; FDA calls the form unidentified.
  • 14.Sung J, et al. (2025). Lysine-Proline-Valine peptide mitigates fine dust-induced keratinocyte apoptosis and inflammation by regulating oxidative stress and modulating the MAPK/NF-κB pathway. Tissue Cell. 95:102837. PMID 40073467Material described as KPV; PM10-stimulated HaCaT and 3D skin models; ROS, ERK/p38, NF-κB, and IL-1β endpoints; exact form requires methods-level confirmation.
  • 15.Cheng J, et al. (2026). Inflammation-triggered self-immolative conjugates enable oral peptide delivery by overcoming gastrointestinal barriers. Sci Adv. 12(3):eaea2989. PMCID PMC12802832proKPV is a distinct self-immolative conjugate with free KPV as a comparator; cell and mouse models.
  • 16.U.S. Food and Drug Administration. (May 12, 2026). Evaluation of KPV-related bulk drug substances: KPV free base and KPV acetate. FDA briefing documentRegulatory review scope is specifically KPV free base and KPV acetate.
  • 17.U.S. Food and Drug Administration. (2026). July 23–24, 2026 Pharmacy Compounding Advisory Committee meeting. Meeting pageScheduling and regulatory-process source; KPV is listed for July 23, 2026.
  • 18.Health Canada. (April 9, 2026). Think twice before injecting peptides bought online: unauthorized products can seriously harm your health. Health Canada advisoryCanadian authorization advisory; it does not provide KPV-specific clinical endpoint evidence.