KPV: Anti-Inflammatory Peptide Profile
Your immune system runs on molecular signals. When tissue is damaged or infected, a cascade of inflammatory molecules rushes to the scene — cytokines like TNF-alpha, IL-6, and IL-1 beta orchestrate the response, recruiting white blood cells and ramping up local defenses.
Your immune system runs on molecular signals. When tissue is damaged or infected, a cascade of inflammatory molecules rushes to the scene — cytokines like TNF-alpha, IL-6, and IL-1 beta orchestrate the response, recruiting white blood cells and ramping up local defenses. This is inflammation doing its job. The problem starts when it doesn't stop.
Chronic, unresolved inflammation drives conditions from inflammatory bowel disease to psoriasis to arthritis. Most anti-inflammatory drugs — corticosteroids, NSAIDs, biologics — work by suppressing parts of the immune system. They're effective, but they come with trade-offs: infection risk, tissue thinning, gut damage. Researchers have spent decades looking for molecules that can calm inflammation without crippling immunity.
KPV is one of the more interesting candidates to emerge from that search. It's a tripeptide — just three amino acids long — carved from the tail end of alpha-melanocyte-stimulating hormone (alpha-MSH), a natural hormone your body already produces. Despite its tiny size, KPV retains the anti-inflammatory power of its much larger parent molecule. Preclinical research has shown it can reduce intestinal inflammation, fight skin damage, and kill pathogens — all without suppressing the immune system the way steroids do. No human clinical trials have been completed yet, and KPV is not approved for medical use — but the science behind it is worth understanding.
Table of Contents
- Quick Facts
- What Is KPV?
- The Alpha-MSH Connection
- How KPV Works: Mechanisms of Action
- Research Evidence
- Administration and Dosing in Research
- Safety Profile and Side Effects
- Legal and Regulatory Status
- Limitations of Current Research
- Frequently Asked Questions
- The Bottom Line
Quick Facts
| Property | Detail |
|---|---|
| Full Name | Lysine-Proline-Valine (Lys-Pro-Val) |
| Type | Tripeptide (3 amino acids) |
| Parent Molecule | Alpha-melanocyte-stimulating hormone (alpha-MSH) |
| Position | C-terminal fragment, alpha-MSH residues 11-13 |
| Molecular Formula | C₁₇H₃₂N₆O₄ |
| Molecular Weight | 384.48 g/mol |
| CAS Number | 112965-21-6 |
| Primary Mechanism | NF-kB pathway inhibition |
| Research Areas | IBD/colitis, skin inflammation, wound healing, antimicrobial |
| Administration Routes | Oral, topical, subcutaneous (research settings) |
| FDA Status | Not approved; Category 2 bulk drug substance |
| Human Clinical Trials | None completed |
What Is KPV?
KPV is a tripeptide made up of three amino acids: lysine (K), proline (P), and valine (V). The single-letter abbreviation of each amino acid gives the peptide its name. It corresponds to positions 11, 12, and 13 of alpha-MSH — the very end of the molecule, known as the C-terminal sequence.
What makes KPV unusual is the mismatch between its size and its biological activity. Most bioactive peptides need at least a dozen amino acids to do anything meaningful. KPV retains the anti-inflammatory potency of its 13-amino-acid parent hormone while being small enough for oral absorption — something most therapeutic peptides can't do.
This small size also means KPV lacks the hormonal baggage of full-length alpha-MSH. It doesn't activate melanin production (so it won't darken skin the way Melanotan II does), and it doesn't appear to interfere with the hypothalamic-pituitary-adrenal axis. Researchers have identified it as the minimum effective sequence for calming immune overactivity.
D.B. Richards and J.M. Lipton published early work on KPV's antipyretic effects in 1984. Hiltz and Lipton followed up in 1989 with a study demonstrating the anti-inflammatory activity of the C-terminal fragment. Since then, research groups have investigated KPV in models of colitis, dermatitis, wound infection, and other inflammatory conditions.
The Alpha-MSH Connection
To understand KPV, you need to understand where it comes from.
Alpha-MSH is a 13-amino-acid peptide hormone produced from a large precursor protein called proopiomelanocortin (POMC). POMC is a molecular Swiss Army knife — enzymes slice it into multiple hormones depending on the tissue: ACTH (the stress hormone), beta-endorphin (the natural painkiller), and the melanocyte-stimulating hormones (alpha-MSH, beta-MSH, gamma-MSH).
Alpha-MSH is best known for stimulating melanin production in skin cells, which is why it belongs to the melanocortin family. But starting in the 1980s, researchers discovered that alpha-MSH has a second life as a potent anti-inflammatory and immunomodulatory peptide. It's produced not just in the pituitary gland but also in skin cells, gut epithelium, and immune cells — wherever inflammation needs to be managed locally.
Alpha-MSH works through a family of five melanocortin receptors (MC1R through MC5R). MC1R, found on immune cells, keratinocytes, and melanocytes, is the primary receptor mediating its anti-inflammatory effects. When alpha-MSH binds MC1R, it elevates cyclic AMP inside the cell, which triggers downstream signaling that suppresses inflammatory gene expression.
The melanocortin system has become a rich area of drug development. Melanotan II targets melanocortin receptors for tanning and sexual function (with significant side effects). Setmelanotide, an MC4R agonist, is FDA-approved for certain genetic obesity disorders. The question with KPV is whether this tiny fragment can deliver the anti-inflammatory benefits without the broader hormonal effects.
The preclinical answer appears to be yes. Multiple studies have confirmed that KPV replicates — and in some cases exceeds — the anti-inflammatory activity of full-length alpha-MSH. A 2017 study in Molecular Therapy found that KPV exerted a stronger anti-inflammatory effect than alpha-MSH in colonic cell models. It's a more focused tool: anti-inflammatory without the pigmentation, appetite, and sexual function effects.
How KPV Works: Mechanisms of Action
KPV's anti-inflammatory effects converge on one of the most studied molecular targets in immunology: NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells).
NF-kB: The Master Inflammatory Switch
NF-kB is a transcription factor that sits in the cytoplasm of nearly every cell, held inactive by an inhibitor protein called IkB-alpha. When the cell detects danger signals, enzymes degrade IkB-alpha, freeing NF-kB to travel into the nucleus and switch on hundreds of pro-inflammatory genes — cytokines like TNF-alpha, IL-6, and IL-1 beta, adhesion molecules, and enzymes like COX-2.
KPV interrupts this process at multiple points. Research in human bronchial epithelial cells showed that KPV stabilizes IkB-alpha, keeping NF-kB locked in the cytoplasm. KPV also enters the nucleus and blocks the interaction between the NF-kB subunit p65 (RelA) and the importin protein (Imp-alpha-3) that carries it through the nuclear pore — specifically competing for the importin-alpha armadillo domains 7 and 8 on p65.
The result: cells treated with KPV produce dramatically less TNF-alpha, IL-6, IL-8, and IL-1 beta. Studies have demonstrated dose-dependent inhibition of NF-kB activity, MMP-9, and eotaxin secretion at nanomolar concentrations.
The PepT1 Transport Mechanism
Researchers initially assumed KPV worked through melanocortin receptors, like its parent molecule. But a landmark 2008 study in Gastroenterology by Dalmasso et al. overturned that assumption: KPV's anti-inflammatory effect in intestinal cells is not melanocortin receptor-mediated.
KPV did not bind to MC1R, MC3R, or MC5R. It did not compete with alpha-MSH for receptor binding. And KPV retained full anti-inflammatory activity in mice with nonfunctional MC1R receptors.
Instead, KPV enters cells through PepT1 (peptide transporter 1), a di/tripeptide transporter normally expressed in the small intestine. This is particularly relevant for IBD because colonic PepT1 expression is upregulated during inflammation — inflamed gut tissue becomes better at absorbing KPV. The sicker the tissue, the more KPV it takes up.
Once inside cells via PepT1, KPV inhibits both NF-kB and MAP kinase (MAPK) pathways. PepT1 showed high affinity for KPV with a Km of approximately 160 micromoles per liter — among the lowest reported for any PepT1 substrate.
MAPK Pathway Suppression
Beyond NF-kB, KPV also suppresses the ERK/p38 MAPK signaling cascade. A 2025 study published in Toxicology demonstrated that KPV inhibits the ERK/p38 MAPK/NF-kB axis and caspase-1 activation driven by reactive oxygen species (ROS) in human keratinocytes. This dual-pathway suppression — both NF-kB and MAPK — helps explain why KPV's anti-inflammatory effects are so consistent across different cell types and disease models.
Oxidative Stress Reduction
KPV also reduces ROS production, the reactive oxygen molecules that act as upstream triggers for both NF-kB and MAPK activation. By cutting off the signal at its source, KPV creates a cascading reduction in inflammatory output. Animal studies in colitis models have confirmed reduced levels of oxidative stress markers including myeloperoxidase (MPO), nitric oxide, and ROS in KPV-treated mice.
Research Evidence
Inflammatory Bowel Disease and Colitis
The strongest body of KPV research focuses on intestinal inflammation, particularly ulcerative colitis. Several preclinical studies have demonstrated significant effects.
Dalmasso et al., 2008 (Gastroenterology): Oral KPV significantly reduced inflammation in two standard colitis models — DSS-induced and TNBS-induced colitis in mice. Treated mice showed reduced body weight loss, lower colonic myeloperoxidase activity, decreased histological inflammation, and lower pro-inflammatory cytokine mRNA levels. This study also identified PepT1 as the transport mechanism.
Laroui et al., 2010 (Gastroenterology): Nanoparticle-encapsulated KPV at just 1 picomole per liter more effectively reduced colitis than free KPV at 100 micromoles per liter in drinking water — a roughly 100-million-fold dose reduction through targeted delivery.
Xiao et al., 2017 (Molecular Therapy): KPV loaded into hyaluronic acid-functionalized nanoparticles (~272 nm) successfully targeted inflamed colonic epithelial cells and macrophages, both accelerating mucosal healing and reducing inflammation. KPV outperformed full-length alpha-MSH in these models.
Viennois et al., 2016 (Cellular and Molecular Gastroenterology and Hepatology): KPV transported by PepT1 prevented colitis-associated carcinogenesis in wild-type mice. In PepT1-knockout mice, KPV had no protective effect — confirming PepT1 transport is required.
Zhang et al., 2024 (Frontiers in Pharmacology): KPV combined with FK506 (tacrolimus) in PepT1-targeted nanoparticles improved body weight, colon length, and disease activity while reducing TNF-alpha, IL-1 beta, and IL-6 in both acute and chronic colitis models.
For readers interested in other peptides studied for gut health, BPC-157 has a parallel body of research on gastrointestinal healing, and our guide to best peptides for gut health compares the evidence across multiple candidates.
Skin Inflammation
KPV research in dermatology spans several areas.
Keratinocyte Protection (2025): A study investigated KPV's effects against fine particulate matter (PM10) damage in human HaCaT keratinocytes. Treatment with 50 micrograms per milliliter of KPV restored cell viability, reduced IL-1 beta secretion, and inhibited ROS-driven ERK/p38 MAPK activation — protecting cells from pollution-induced pyroptosis.
Wound Healing: KPV accelerated wound closure, reduced infection, and produced better cosmetic outcomes in preclinical models. MC1R, which has high affinity for alpha-MSH, is expressed in fibroblasts, keratinocytes, and endothelial cells — all directly involved in wound repair. These benefits occurred at physiological concentrations, suggesting relevance to serious wounds including burns. GHK-Cu is another peptide studied for wound healing through different mechanisms.
Inflammatory Skin Conditions: Animal models have shown alpha-MSH fragments reduce inflammation in contact dermatitis and cutaneous vasculitis. Unlike corticosteroids, KPV does not appear to cause tissue thinning or immune suppression — a meaningful advantage for chronic skin conditions.
Antimicrobial Activity
Cutuli et al. published the landmark antimicrobial study in 2000 in the Journal of Leukocyte Biology. They found that alpha-MSH and its C-terminal tripeptide KPV had direct antimicrobial effects against Staphylococcus aureus (a common bacterial pathogen) and Candida albicans (a fungal pathogen).
Antimicrobial effects occurred across a broad concentration range, including picomolar (physiological) concentrations. KPV significantly inhibited S. aureus colony formation and reduced viability and germ tube formation of C. albicans. The mechanism appeared to involve increased cellular cAMP in the pathogens.
What makes KPV unusual: it didn't reduce neutrophil killing of pathogens. Most anti-inflammatory drugs weaken immune defenses against infection. KPV combined direct antimicrobial action with anti-inflammatory effects while preserving the body's own pathogen-killing capacity. The researchers noted that this "two-in-one action could be especially useful" when infection and inflammation coexist. LL-37 is another antimicrobial peptide with overlapping anti-inflammatory properties, though it works through different mechanisms.
Broader Anti-Inflammatory Applications
Animal models have tested alpha-MSH fragments across allergic contact dermatitis, asthma, rheumatoid arthritis, ocular inflammation, and brain inflammation. A 2012 study showed KPV and gamma-MSH evoked dose-dependent inhibition of NF-kB, MMP-9, IL-8, and eotaxin in bronchial epithelial cells. TB-500 and VIP are other peptides with anti-inflammatory research. Our guide on best peptides for inflammation reduction provides a broader comparison.
Administration and Dosing in Research
One of KPV's practical advantages is its versatility in delivery routes. Most therapeutic peptides are limited to injection because they're broken down in the digestive tract. KPV's tiny size and its affinity for the PepT1 transporter give it options.
Oral Administration
KPV can be delivered orally — a rarity for peptides. The PepT1 transporter actively absorbs KPV, and since PepT1 expression increases during intestinal inflammation, oral KPV has a built-in targeting advantage for gut conditions. Nanoparticle delivery systems have dramatically improved oral efficacy — one study showed effective doses at picomolar concentrations with targeted nanoparticles, versus micromolar concentrations for free KPV.
Topical Application
Experimental formulations have used 0.1-1% cream or gel concentrations for skin conditions and wound healing. KPV acts directly on keratinocytes, fibroblasts, and local immune cells without systemic absorption. Iontophoresis — using low-level electrical current to drive molecules across the skin — has also been explored.
Subcutaneous Injection
Injectable routes (subcutaneous, intravenous, intraperitoneal) bypass absorption barriers, delivering KPV directly into systemic circulation.
Important: No standardized dosing protocol exists for KPV in humans. All dosing information comes from preclinical research, and extrapolating animal doses to human doses requires careful pharmacokinetic analysis that has not been performed for KPV.
Safety Profile and Side Effects
KPV's safety profile looks favorable in preclinical data — but the evidence has significant gaps.
What We Know
In animal studies, KPV has been well tolerated across oral, subcutaneous, intravenous, and topical routes. No significant adverse effects have been reported at therapeutic doses. KPV-loaded nanoparticle formulations showed no measurable cytotoxicity in vitro, even after prolonged exposure.
KPV does not cause skin darkening (it lacks melanogenic activity) and does not appear to suppress immune function — a meaningful distinction from corticosteroids. Reported side effects from off-label clinical use are limited to mild injection site reactions, transient GI upset, and occasional localized redness from topical application.
What We Don't Know
The FDA has stated that it "has not identified any human exposure data on drug products containing KPV administered via any route of administration." This is a critical gap. There are no completed human clinical trials, no long-term safety data, no pharmacokinetic studies in humans, and no data on drug interactions.
Specific unknowns include:
- Chronic use: No data on what happens with months or years of KPV use
- Drug interactions: No studies on how KPV might interact with immunosuppressants, NSAIDs, biologics, or other medications
- Vulnerable populations: No safety data for pregnant or breastfeeding women, children, elderly patients, or immunocompromised individuals
- Dose-response in humans: No human pharmacokinetic or pharmacodynamic data
As a general precaution, pregnant or breastfeeding women and individuals with a history of cancer are typically advised to avoid KPV and similar research peptides. Thymosin Alpha-1 is another immune-modulating peptide where safety data, while more developed, still has notable gaps.
Legal and Regulatory Status
KPV occupies a complicated regulatory space as of early 2026.
FDA Classification: KPV is not approved by the FDA for any indication. It is classified as a Category 2 bulk drug substance — the FDA's designation for substances with "potential significant safety risks." This classification stems from the absence of human safety data, not from demonstrated harm.
Compounding Restrictions: KPV cannot be legally compounded by pharmacies for human use. It lacks FDA approval, GRAS status, a USP monograph, and inclusion on the approved bulks list. This puts it alongside other restricted research peptides, including BPC-157 and TB-500.
Research Use: KPV is legally available as a research chemical labeled "for research use only." It cannot be marketed as a supplement or therapeutic product.
Ongoing Review: The FDA's review of peptide compounding is ongoing. Advocates are pushing for certain peptides to be moved to Category 1 (allowed for compounding) when sufficient safety evidence exists. The Pharmacy Compounding Advisory Committee (PCAC) continues to evaluate.
International Status: KPV is not approved by the EMA or other major regulatory bodies. Regulatory approaches to research peptides vary by country.
Limitations of Current Research
Being honest about what the science does and doesn't show is the most important section in any peptide profile. Here's where KPV stands:
No human clinical trials. Every positive finding in this article comes from cell cultures or animal models. Mouse colitis models don't perfectly mirror human IBD. The leap from "works in mice" to "works in humans" fails more often than it succeeds in drug development.
Publication bias. The available literature on KPV is overwhelmingly positive, which is typical for early-stage research. We don't know how many negative or equivocal studies went unpublished.
Dosing uncertainty. Animal doses cannot be directly translated to humans without pharmacokinetic studies that haven't been done. The dramatically different efficacy between free KPV and nanoparticle-delivered KPV shows how much delivery method matters — and no optimized human delivery system exists.
Mechanism questions remain. The finding that KPV works through PepT1 rather than melanocortin receptors hasn't been fully reconciled with earlier studies suggesting receptor-mediated effects.
Limited pathogen spectrum. Antimicrobial effects have been demonstrated against S. aureus and C. albicans only. Activity against MRSA, gram-negative bacteria, and other fungi is not established.
No long-term data. Even in animal studies, most experiments lasted days to weeks. Chronic inflammatory conditions need treatments that work safely for months or years.
Frequently Asked Questions
What is KPV peptide used for in research?
KPV is studied primarily for its anti-inflammatory properties. The main research areas are inflammatory bowel disease (particularly ulcerative colitis), inflammatory skin conditions (dermatitis, psoriasis, wound healing), and antimicrobial applications. All research to date is preclinical — conducted in cell cultures and animal models — with no completed human clinical trials.
How is KPV different from alpha-MSH?
KPV is the C-terminal tripeptide fragment of alpha-MSH — 3 amino acids versus alpha-MSH's 13. Despite this size reduction, KPV retains anti-inflammatory activity. It does not stimulate melanin production, does not appear to affect appetite or sexual function, and can potentially be absorbed orally through the PepT1 transporter.
Can KPV be taken orally?
In animal studies, yes. KPV's affinity for the PepT1 transporter allows oral absorption — unusual for a peptide. Mouse studies show oral KPV reduces colitis severity. However, no human studies have confirmed oral bioavailability, dosing, or efficacy.
Is KPV safe?
Preclinical data suggests KPV is well tolerated in animals, with no significant adverse effects reported at therapeutic doses. It does not appear to suppress immune function. However, there are no human safety studies, no long-term data, and the FDA has classified KPV as a Category 2 substance due to the absence of human exposure data. Anyone considering KPV should consult a licensed healthcare provider.
How does KPV compare to BPC-157 for gut health?
They work through different mechanisms. KPV targets the NF-kB pathway via PepT1 transport and has been studied in colitis models. BPC-157 appears to work through growth factor modulation, nitric oxide pathways, and angiogenesis. Neither has completed human clinical trials. Our best peptides for gut health guide compares the evidence.
Is KPV legal to buy?
KPV is available for purchase as a research chemical labeled "for research use only." It is not approved as a medication or supplement for human use. Under current FDA rules, it cannot be compounded by pharmacies for patient use. Legal status varies by country, and regulations continue to change.
Does KPV have antimicrobial properties?
Yes, in laboratory studies. Research published in the Journal of Leukocyte Biology demonstrated that KPV has direct antimicrobial activity against Staphylococcus aureus and Candida albicans at concentrations as low as the picomolar range. Notably, KPV preserved neutrophil killing capacity rather than suppressing it — a meaningful distinction from many anti-inflammatory drugs. LL-37 is another antimicrobial peptide if this area interests you.
The Bottom Line
KPV is a three-amino-acid peptide with a disproportionately large body of preclinical evidence behind it. The research on intestinal inflammation is particularly developed — multiple studies show oral KPV reducing colitis severity in animal models, with nanoparticle delivery dramatically improving efficacy. The PepT1-mediated uptake mechanism is elegant: inflamed gut tissue upregulates the very transporter that absorbs KPV, creating a natural targeting system.
The antimicrobial data adds another dimension. A peptide that fights both inflammation and infection without suppressing immune function would address a real gap in therapeutics. The skin research points toward applications in wound healing and environmental damage protection.
But none of this has been validated in humans. Zero clinical trials. No pharmacokinetic data in people. No long-term safety studies. The FDA has not identified any human exposure data for KPV — a fact behind its Category 2 classification and current compounding ban. Promising preclinical data is the starting line, not the finish line.
KPV's properties — oral bioavailability, self-targeting to inflamed tissue, dual anti-inflammatory and antimicrobial activity — make it a strong candidate for eventual clinical development. What it needs is rigorous human trials that either confirm or challenge what the preclinical work suggests. Anyone interested in KPV should discuss it with a qualified healthcare provider and follow the published research rather than vendor marketing claims.
This article is for educational purposes only and does not constitute medical advice. KPV is a research compound not approved for human therapeutic use. Always consult a licensed healthcare professional before considering any peptide therapy.
Last updated: February 2026