KPV—short for Lys‑Pro‑Val—is a three–amino‑acid fragment of α‑melanocyte‑stimulating hormone (α‑MSH) that researchers study for anti‑inflammatory activity at barrier tissues like the gut, skin, and ocular surface. In preclinical models, KPV dampens NF‑κB–driven cytokine signaling without the pigmenting effects associated with α‑MSH, which is why it’s frequently explored as a non‑pigmenting melanocortin‑derived tripeptide for inflammation biology. (OUP Academic)
Fast Answer / Executive Summary (40–60 words)
KPV is an α‑MSH–derived tripeptide (Lys‑Pro‑Val) studied for its ability to reduce NF‑κB–mediated inflammation, particularly at epithelial barriers. Mechanistically, it can act independently of classical melanocortin receptors and is transported by the PepT1 di/tripeptide transporter in gut epithelium; animal and cell studies show reduced cytokine signaling and tissue injury. (PubMed)
KPV: Entity Properties (for researchers)
| Property | Detail |
|---|---|
| Aliases / Synonyms | KPV; α‑MSH(11–13); ACTH(11–13) |
| Family / Pathway | Melanocortin–derived tripeptide; interacts with NF‑κB pathways; epithelial uptake via PepT1 (SLC15A1) in gut models |
| Sequence (AA) | H‑Lys‑Pro‑Val‑OH |
| Molecular Weight (Da) | ~342.43 (free acid) |
| CAS (free acid) | 67727‑97‑3 |
| Typical Diluent(s) (educational) | Sterile water for injection (SWFI), 0.9% saline, or bacteriostatic water (per lab SOPs and supplier CoA) |
| Example Concentration(s) used in research (educational) | 10 nM in intestinal epithelial cell assays; 100 μM in drinking water in murine colitis models; 1–10 μM topically in corneal experiments |
| Storage (lyophilized / after reconstitution) (educational) | Lyophilized at –20 °C (dry, dark); aliquot and store at 2–8 °C (short term) or –20 °C (longer term) post‑reconstitution, per lab SOPs/CoA |
Notes/Sources for properties: α‑MSH(11–13) identity and non‑pigmenting profile (Endocrine Reviews); epithelial PepT1 transport and 10 nM cell data + 100 μM oral water in mice (Gastroenterology 2008); corneal 1–10 μM topical use (Exp Eye Res 2006); chemical identity/MW (PubChem). (OUP Academic)
Core Concepts & Key Entities
What is KPV biologically? KPV (Lys‑Pro‑Val) is the C‑terminal tripeptide of α‑MSH. It preserves α‑MSH’s anti‑inflammatory signal without the melanogenic (pigmenting) effect—an important distinction for dermatology and ocular research contexts. This non‑pigmenting profile is a major reason KPV is studied as a targeted anti‑inflammatory tripeptide. (OUP Academic)
How does KPV interface with inflammatory pathways? In cell and animal models, KPV reduces NF‑κB activation and the downstream transcription of pro‑inflammatory cytokines (e.g., TNF‑α, IL‑6, IL‑8) in epithelial and immune cells. In intestinal models, this anti‑inflammatory effect is linked to PepT1‑mediated uptake of KPV into epithelial cells. (PubMed)
Is KPV a classic melanocortin receptor agonist? Not necessarily. Although α‑MSH signals through melanocortin receptors (MC1R–MC5R), KPV’s anti‑inflammatory effect can occur independently of melanocortin receptor–cAMP signaling in intestinal epithelium, indicating a distinct pharmacology for this minimal tripeptide. (PubMed)
Where is KPV most studied?
- Gut epithelium: colitis models (DSS, TNBS), epithelial PepT1 transport, NF‑κB dampening. (PubMed)
- Skin / keratinocytes: α‑MSH–related peptides reduce TNF‑α‑induced NF‑κB activity; KPV is of particular interest because it lacks pigmenting activity. (PubMed)
- Ocular surface: corneal wound‑healing models show faster re‑epithelialization with topical KPV. (PubMed)
- CNS injury models: tripeptide α‑MSH(11–13) reduced tissue damage after controlled cortical impact in mice. (PLOS)
Therapeutic‑outcomes orientation: Across these systems, the unifying outcome is less NF‑κB–driven inflammation at barrier tissues with minimal pigmentary change, which is valuable in research focused on epithelial integrity, wound repair, and cytokine normalization. (OUP Academic)
Mechanism of Action (Answer‑first)
KPV reduces NF‑κB signaling in epithelial and immune cells; in gut models this depends on PepT1 uptake rather than classical melanocortin receptor signaling. In Caco‑2/HT29 intestinal cells, KPV (10 nM) decreased NF‑κB–luciferase activity and IκB‑α degradation; in mice, KPV added to drinking water (100 μM) reduced DSS/TNBS colitis severity and cytokine expression. (PubMed)
Independence from melanocortin receptors. While α‑MSH activates cAMP via MC1R/MC3R/MC5R, KPV’s anti‑inflammatory effect in epithelium did not mirror α‑MSH’s cAMP profile, supporting a receptor‑independent or transporter‑facilitated mechanism. This helps explain KPV’s distinct non‑pigmenting profile vs. α‑MSH. (PubMed)
NF‑κB linkage to outcomes. Because NF‑κB orchestrates many inflammatory genes at barrier tissues, small decreases in NF‑κB activation can yield measurable improvements in tissue integrity, wound closure, and symptom‑relevant cytokine profiles. The NF‑κB centrality in skin and ocular surface inflammation is well‑documented, contextualizing KPV’s mechanism for dermatologic and ocular applications. (PubMed)
Information‑gain insight: Think of KPV as a “precision tripeptide” that rides epithelial transport (PepT1) to quieten the local transcriptional noise (NF‑κB) that keeps barrier tissues inflamed—without the pigment changes that complicate α‑MSH. That combination of route + target + cosmetic neutrality is the distinctive research value‑add. (PubMed)
Evidence by System (What researchers actually observed)
Gut & Intestinal Barrier
Key finding: Oral KPV (in drinking water, 100 μM) reduced colitis severity in DSS/TNBS models, with lower cytokines and histologic inflammation; PepT1 expression/transport was required for the epithelial anti‑inflammatory effect. This points to a transporter‑targeted approach for oral delivery. (PubMed)
Why it matters for outcomes: In IL‑1β/TNF‑α environments that resemble IBD‑like epithelial stress, NF‑κB suppression can reduce neutrophil influx and chemokines (e.g., IL‑8), translating to less mucosal injury in preclinical models—an endpoint that maps closely to disease activity indices researchers track. (PubMed)
Skin & Keratinocytes
Key finding: α‑MSH–related peptides (including KPV and KP‑D‑V) inhibit TNF‑α–stimulated NF‑κB activation in keratinocyte models; KPV avoids pigmenting action while preserving anti‑inflammatory effects. This mechanistic separation is central for skin‑facing research where pigmentation is a confounder or safety concern. (PubMed)
Why it matters: In chronic skin inflammation, NF‑κB modulates keratinocyte proliferation/differentiation and cytokine release; turning down NF‑κB is associated with better epidermal homeostasis and less inflammatory signaling, a desired outcome across dermatitis research. (PubMed)
Ocular Surface & Wound Repair
Key finding: Topical KPV (1–10 μM) accelerated corneal epithelial wound closure in rabbits; NO signaling appeared contributory because the effect was diminished by L‑NAME. The whole epithelial sheet re‑epithelialized in KPV‑treated corneas by ~60 h, whereas placebo lagged significantly. (PubMed)
Why it matters: The corneal epithelium is a canonical barrier tissue with rapid turnover. KPV’s ability to shorten closure time and support epithelial viability suggests research utility in injury models where rapid, scar‑sparing re‑epithelialization is desired. (PubMed)
CNS Injury (Exploratory)
Key finding: Single α‑MSH(11–13) administration decreased tissue damage after controlled cortical impact in mice, a model of traumatic brain injury. Although outside barrier‑epithelial focus, it reinforces KPV’s broader anti‑inflammatory footprint. (PLOS)
Delivery and Handling Considerations (Educational)
Oral—leveraging PepT1. In mouse colitis models, KPV in drinking water (100 μM) reduced inflammation, implicating PepT1 as a route for enterocyte uptake. For researchers, this hints that oral/topical epithelial exposure can be rational if the target tissue expresses di/tripeptide transporters (PepT1 in small intestine, inducible in inflamed colon). (PubMed)
Topical / Transdermal. Skin delivery is challenging for hydrophilic tripeptides. Microneedles and iontophoresis (and particularly their combination) significantly increased KPV permeation across human skin in vitro—far beyond passive diffusion—making device‑assisted transdermal delivery a viable research tactic. (PubMed)
Ocular. In preclinical models, topical KPV on the cornea improved re‑epithelialization; in eye research, vehicle selection and dosing frequency (e.g., multiple daily instillations) can materially affect outcomes. (PubMed)
General lab handling (educational, not medical): Short peptides are commonly reconstituted in sterile aqueous solutions (e.g., SWFI, PBS, or bacteriostatic water) and aliquoted to minimize freeze–thaw cycles, following local SOPs/CoA. (Always align procedures to your institution’s quality system.)
Step‑by‑Step / How‑To (Designing a KPV Experiment)
1) Define the barrier tissue and readouts
Specify the primary tissue (gut epithelium, keratinocytes, cornea) and primary endpoint (NF‑κB activity, IL‑8/TNF‑α mRNA, histology, wound‑closure time).
2) Choose delivery route to match the tissue
For gut, consider oral exposure; for skin, microneedles ± iontophoresis to overcome hydrophilicity; for cornea, topical with validated dosing frequency. (PubMed)
3) Anchor concentrations to literature
In vitro: ~10 nM (intestinal lines) or 1–10 μM (corneal cells). In vivo (murine colitis): ~100 μM in drinking water. Adjust based on pilot toxicity and target engagement. (PubMed)
4) Instrument NF‑κB and cytokine outputs
Use NF‑κB reporter assays, IκB‑α westerns, and qPCR/ELISA for IL‑8, TNF‑α, IL‑6 to quantify pathway effects. (PubMed)
5) Control for melanocortin pathways
Include α‑MSH (positive control) and receptor antagonists when relevant to clarify KPV’s MCR‑independent activity. (PubMed)
6) Plan for transporter confirmation (gut)
Use PepT1 inhibitors or knockdown and radiolabeled uptake where feasible to verify PepT1 dependence. (PubMed)
7) Predefine clinical‑analog endpoints
Map readouts (e.g., histologic scoring, wound closure time) to clinically meaningful constructs to boost translational relevance.
Comparison / Alternatives (“KPV vs BPC‑157 vs TB‑500”)
Answer‑first: KPV excels when NF‑κB–dominant epithelial inflammation and non‑pigmenting action are priorities; BPC‑157 has broad pro‑healing/angiogenic signals across many preclinical tissues; Thymosin β4 (TB‑500) is prominent in wound‑healing/angiogenesis research and corneal repair literature.
Quick Comparison Table (research‑focused)
| Attribute | KPV (α‑MSH[11–13]) | BPC‑157 (GEPPPGKPADDAGLV) | Thymosin β4 (TB‑500) |
|---|---|---|---|
| Primary signal(s) | NF‑κB down‑modulation; PepT1‑facilitated epithelial uptake; MCR‑independent in epithelium | Angiogenesis/NO modulation; multi‑tissue cytoprotection; broad pleiotropy | Actin‑binding/cell migration; angiogenesis; ECM remodeling |
| Barrier tissue focus | Gut/skin/cornea; non‑pigmenting melanocortin fragment | GI tract, skin, tendon, nerve (preclinical breadth) | Skin/cornea/heart; robust dermal & corneal data |
| Representative evidence | DSS/TNBS colitis ↓ inflammation with oral 100 μM KPV; keratinocyte NF‑κB ↓; corneal re‑epithelialization ↑ | Frontiers/GL reviews summarizing multi‑system wound and vascular protection (mostly preclinical) | Classic corneal and wound‑healing studies; clinical‑leaning corneal programs |
| Pigmenting effects | Non‑pigmenting by design (vs α‑MSH) | Not melanotropic | Not melanotropic |
| Typical research delivery | Oral (PepT1), topical (device‑assisted skin), ocular drops | Oral, parenteral, topical (varied preclinical) | Topical/ocular, parenteral |
| Evidence maturity | Focused, mechanistic epithelial data; limited human trials | Large preclinical body; limited human clinical data to date | Substantial preclinical; selected clinical explorations in eye/wounds |
Sources: KPV (Endocrine Reviews; Gastroenterology; J Invest Dermatology; Exp Eye Res); BPC‑157 (Frontiers Pharmacology 2021; Gut and Liver 2020 reviews); TB‑4 (peer‑reviewed wound/cornea literature). (OUP Academic)
Bottom line for “best” choice: If your primary endpoint is NF‑κB‑driven epithelial inflammation with a cosmetic constraint (non‑pigmenting), KPV is the targeted pick. For broad wound angiogenesis/vascular stability across tissues, BPC‑157 or Thymosin β4 often make more sense. (OUP Academic)
Templates / Checklist / Example
Copy‑ready Researcher Checklist (KPV)
- Define the tissue (gut, skin, cornea) and endpoint (NF‑κB, cytokines, closure time).
- Confirm KPV identity and purity against the CoA before use.
- Select delivery to match tissue: oral (PepT1); microneedles/iontophoresis for skin; topical drops for cornea. (PubMed)
- Anchor initial concentrations to literature (10 nM epithelial cells; 1–10 μM cornea; 100 μM drinking water in mice). (PubMed)
- Instrument NF‑κB (reporters/IκB‑α) and cytokines (IL‑8, TNF‑α, IL‑6). (PubMed)
- Include α‑MSH controls and MCR antagonism if pathway dissection is part of the goal. (PubMed)
- Add transporter controls (PepT1 competition/knockdown) for mechanism confirmation. (PubMed)
- Pre‑register analysis, power for primary outcome, and blinding plan.
- Document storage, aliquoting, and freeze–thaw minimization per SOPs.
- Report methods transparently to support reproducibility and peer review.
FAQs (NLP‑friendly, answer‑first)
1) What is KPV?
KPV is the C‑terminal tripeptide (Lys‑Pro‑Val) of α‑MSH studied for anti‑inflammatory effects at epithelial barriers. It reduces NF‑κB activation and pro‑inflammatory cytokines, often without melanocortin receptor dependence in intestinal epithelium, and shows efficacy in colitis, keratinocyte, and corneal wound models. (PubMed)
2) How does KPV work?
KPV works by reducing NF‑κB activation and downstream cytokine expression, a central pathway in barrier‑tissue inflammation. In the gut, its effect requires PepT1‑mediated transport into epithelial cells, distinguishing it from classical α‑MSH receptor signaling. (PubMed)
3) Does KPV cause skin pigmentation like α‑MSH?
No—KPV is considered non‑pigmenting while preserving anti‑inflammatory actions of α‑MSH. This mechanistic separation underpins interest in dermatology research where pigment changes are undesirable. (OUP Academic)
4) What concentrations of KPV are used in studies?
Studies commonly use ~10 nM in epithelial cell assays, 1–10 μM topically in corneal models, and ~100 μM in drinking water in murine colitis. These are model‑specific, non‑clinical research exposures, not human dosing. (PubMed)
5) How does KPV compare to BPC‑157 or TB‑500?
KPV is a focused anti‑inflammatory tripeptide for epithelial NF‑κB signaling, whereas BPC‑157 and TB‑500 show broader pro‑healing and angiogenic effects across many preclinical tissues. The “best” choice depends on the endpoint (NF‑κB vs. wound angiogenesis). (Frontiers)
6) Is there human clinical evidence for KPV?
Human randomized trials are limited. Most data are from cell and animal models (gut, skin, cornea, CNS), which justify mechanistic and device‑assisted delivery research but don’t establish clinical efficacy or safety for therapeutic use. (PubMed)
Next Steps
If your research is focused on epithelial NF‑κB signaling and you need a non‑pigmenting α‑MSH–derived tool, KPV is a strong candidate. For step‑by‑step educational protocols on single‑vial preparation and study design, see our internal guides: KPV 5 mg Vial: Dosage Protocol (Educational) and KPV 10 mg Vial: Dosage Protocol (Educational).
When you’re ready to source research‑grade material, you can purchase KPV 10 mg (PureLabPeptides). (For research use only; not for human consumption.)
Key takeaway: KPV is a transporter‑savvy, non‑pigmenting tripeptide that quiets epithelial NF‑κB signaling—making it a precise tool for gut, skin, and corneal inflammation research. (PubMed)