About KPV
KPV is the C-terminal tripeptide of alpha-MSH and is studied for its anti-inflammatory effects in IBD models, dermatology, and wound healing. Often used adjunctively with BPC-157 in gut-focused research.
Gut Health
KPV
Tripeptide Anti-inflammatory
A C-terminal tripeptide of alpha-MSH studied for anti-inflammatory effects in IBD models.
PreclinicalResearch use only
Where to buy
Vendor offerings
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Best $/mg
Atomik LabzTestedCAPSULES – KPV 500mcg x 90 Capsules
EVERYDAY25$129.00
$258.00/mg · 500mcg
Solution PeptidesTestedCAPSULES – KPV 500mcg x 90 Capsules
EVERYDAY15$129.00
$258.00/mg · 500mcg
Evidence level
Preclinical only
The C-terminal tripeptide of alpha-MSH (Lys-Pro-Val) with anti-inflammatory activity in preclinical IBD, dermatitis, and wound-healing models. Human data is minimal.
Mechanism
Modulates melanocortin signaling and NF-kB pathways.
Researched benefits
Gut anti-inflammation (preclinical)
In DSS- and TNBS-induced colitis models in mice, oral and rectal KPV reduce histological inflammation, neutrophil infiltration, and pro-inflammatory cytokine expression at low microgram doses.
NF-κB pathway suppression
KPV inhibits nuclear translocation of NF-κB in stimulated macrophages and intestinal epithelial cells, reducing TNF-α, IL-6, and IL-1β output in cell culture.
Skin and wound-healing applications
Topical KPV has been studied in atopic dermatitis and acne models; reduced erythema and accelerated re-epithelialization were reported in small preclinical experiments.
Oral bioavailability
Unusually for a peptide, KPV appears to be absorbed intact via the PepT1 transporter in intestinal epithelium, enabling oral dosing in colitis models.
Risks & cautions
- moderate
Limited human safety data
Most data is rodent. A few small dermatology trials exist but long-term human use is uncharacterized.
- moderate
Immunomodulation
Suppressing NF-κB chronically has theoretical implications for infection clearance and tumor surveillance. Not demonstrated in humans but worth considering.
- low
Pigmentation considerations
Unlike full-length alpha-MSH, KPV does not bind melanocortin-1 receptor strongly and is not expected to cause hyperpigmentation. Mentioned because the parent molecule does.
- low
Injection-site reactions
Standard subcutaneous risks; oral and topical use have different (mostly milder) tolerability profiles.
Dosing
200–500 mcg daily, subcutaneous or oral, often run in 4–8 week courses.
- Conservative
- 200 mcg/day
- Standard
- 500 mcg/day
- Aggressive
- 500 mcg twice daily (uncommon)
Vial sizes
5mg / 10mg
Half-life
Short
Route
subcutaneous, oral
Reconstitute with bacteriostatic water for injection. Oral forms exist but absorption depends on PepT1 expression, which can be downregulated in inflamed gut tissue. Often stacked with BPC-157 in gut-focused protocols.
Contraindications
- Active malignancy — theoretical concern with chronic NF-κB suppression
- Active infection requiring full immune response
- Pregnancy or breastfeeding — no data
In depth
Background
KPV (Lys-Pro-Val) is the C-terminal tripeptide of alpha-melanocyte-stimulating hormone (α-MSH, residues 11–13). Interest in the fragment grew when researchers noticed that α-MSH's anti-inflammatory activity could be partially recapitulated by its C-terminal sequence — without the pigmentation effects mediated by its N-terminal melanocortin-receptor binding domain.
KPV's small size makes it unusually stable and orally absorbable, which has made it attractive for gut-targeted research.
Mechanism in depth
Proposed and partially demonstrated mechanisms:
- NF-κB inhibition. KPV blocks IκB phosphorylation and nuclear translocation of p65, dampening transcription of pro-inflammatory cytokines.
- Direct entry into immune cells. KPV is taken up by macrophages and intestinal epithelial cells via PepT1, the same transporter that absorbs dietary di- and tri-peptides.
- Mast cell stabilization. In skin and gut models, KPV reduces histamine release from activated mast cells.
- MC1R-independent activity. Unlike the parent α-MSH, KPV does not stimulate melanocyte pigmentation appreciably.
The PepT1 pathway is what enables oral and intracolonic dosing — uncommon in peptide pharmacology.
Preclinical evidence
Most data is in mice and rats:
- DSS and TNBS colitis. Oral KPV (low microgram per kg) reduced macroscopic and microscopic colitis scores, MPO activity, and TNF-α / IL-6 in colon homogenate. Effects were comparable to corticosteroid arms in some studies.
- Atopic dermatitis models. Topical KPV reduced ear thickness and inflammatory infiltrate in oxazolone-sensitized mice.
- Wound healing. Faster re-epithelialization in incisional wound models.
- Acne / sebaceous gland studies. In vitro KPV reduced lipogenesis and inflammatory cytokine output in sebocyte cultures.
Human evidence
Limited:
- A small open-label series in mild ulcerative colitis reported symptomatic improvement, but the study was underpowered for hard endpoints.
- Dermatology case reports describe topical KPV use for inflammatory skin conditions.
- No large randomized trial has been published.
Stack synergy
Common combinations:
- BPC-157 — frequently paired in gut protocols; complementary mechanisms (BPC-157 hits angiogenesis and growth factor signaling; KPV hits NF-κB).
- Larazotide or low-dose naltrexone — used by some clinicians for autoimmune-spectrum gut disease, though evidence for combined use is anecdotal.
- Topical niacinamide or azelaic acid in dermatology stacks.
Open questions
- Does KPV have meaningful efficacy in actual human IBD compared to mesalamines, biologics, or JAK inhibitors? No head-to-head data.
- What is the long-term safety profile of chronic NF-κB suppression at the doses used?
- Is oral bioavailability sufficient for systemic effects, or only effective when the target is gut epithelium?
References
- 1.Kannengiesser K. et al. — Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease (Inflammatory Bowel Diseases, 2008)
- 2.Dalmasso G. et al. — PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation (Gastroenterology, 2008)
- 3.Brzoska T. et al. — Alpha-MSH and related tripeptides: biochemistry, anti-inflammatory and protective effects in vitro and in vivo (Endocrine Reviews, 2008)