KPV

What Is KPV ?

KPV (Ac-KPV-NH2) is a strong anti-inflammatory peptide that has shown promise in several disease conditions. The most active research is in treating inflammatory bowel disease, where the peptide has shown great promise. Studies in wound healing also show that Ac-KPV-NH2 and other alpha-MSH derivatives may offer many benefits that speed healing, reduce infection, fight inflammation, and lead to better cosmetic results. Ac-KPV-NH2 and similar peptides could become key treatments not just for wound healing, but for reducing scars after surgery.

Amino Acid Sequence: Lys-Pro-Val
Molecular Formula: C17H32N6O4
Molecular Weight: 384.48 g/mol
PubChem CID: 125672
CAS Number: 112965-21-6
Synonyms: MSH (11-13), ACTH(11-13), alpha-MSH(11-13)

Intestinal Inflammation
Perhaps the most important finding from Ac-KPV-NH2 is that the peptide reduces gut inflammation. In mouse models of inflammatory bowel disease (IBD), Ac-KPV-NH2 shows strong results, cutting down on inflammatory cells, MPO activity, and overall signs of inflammation in tissue samples. Mice treated with Ac-KPV-NH2 in the study recovered faster and gained more weight than those given a placebo.
Further studies on ways to deliver Ac-KPV-NH2 have shown that loading it onto nanoparticles coated with hyaluronic acid helps direct its anti-inflammatory effects to the right spots in the intestine. This leads to faster healing of the gut lining and relief from inflammation through a strong reduction in TNF-alpha in mouse models. In many ways, Ac-KPV-NH2 is a more effective and targeted way to reduce inflammation in IBD without affecting TNF-alpha elsewhere in the body. The benefit of modifying Ac-KPV-NH2 is improving how well it works when taken by mouth. This does not make the peptide stronger, but it does affect its potency and thus the total dose needed for results.
Research suggests TNF-alpha is not the only inflammatory factor that Ac-KPV-NH2 affects. The peptide also lowers NF-kappaB and mitogen-activated protein kinase activity. These effects work together with TNF-alpha reduction to ease inflammatory changes in the gut. Mice treated with Ac-KPV-NH2 have much less colon infiltration and normal colon lengths compared to controls.
Of interest in the graph above is the fact Ac-KPV-NH2 appears to only have an effect in the setting of extreme inflammation. It has almost no effect in normal tissue. At least part of the reason for this is that Ac-KPV-NH2 enters colon cells via a transporter that is boosted during inflammation. This suggests Ac-KPV-NH2 may be an effective preventive or ongoing medication for IBD. It can be safely taken even during quiet periods because it has no effect then. It is available when needed and simply passed out otherwise. Professor Didier Merlin, who has led much research into Ac-KPV-NH2’s potential gut benefits, recently found the peptide enters colon cells via PepT1, a protein channel expressed in large amounts in the intestine only during inflammation. This explains why Ac-KPV-NH2 works better in already inflamed settings. It also suggests a new way to deliver drugs that could apply to many conditions. By targeting proteins changed in disease, even if not directly causing it, drugs could focus on certain areas. This could mean lower doses for drugs with serious side effects and creating drugs that, while not strong alone, are powerful in the right disease state.
General Anti-Inflammatory
As far back as 1984, studies in rabbits showed Ac-KPV-NH2 is a powerful anti-inflammatory and fever reducer. In this case, however, Ac-KPV-NH2 had lower strength than the full alpha-MSH molecule. This led scientists at the time to think Ac-KPV-NH2 lacked some part of alpha-MSH needed for full fever-reducing activity. What followed was decades of research testing various modified forms of alpha-MSH.
Perhaps the biggest lesson from these tests is that alpha-MSH and several similar compounds all reduce inflammation in a wide range of diseases. So far, the molecules have been tested in fever, irritant and allergic skin inflammation, blood vessel inflammation, fibrosis, arthritis, and inflammation of the eyes, brain, lungs, and gut. In all cases, alpha-MSH is the strongest anti-inflammatory. Unfortunately, it has one major side effect—it causes skin darkening. Ac-KPV-NH2, however, does not have this side effect. Even though Ac-KPV-NH2 is not as strong as full alpha-MSH, its lack of side effects means boosting levels to reach desired effects is possible in most cases.
The difference in strength has been found to be small at best, as most anti-inflammatory effects of alpha-MSH come from the Ac-KPV-NH2 section. What is interesting, though, is that the parent molecule seems better at stopping late-stage inflammatory reactions. In contact dermatitis, for instance, alpha-MSH does a better job preventing an allergic inflammatory response two weeks after first exposure. This suggests alpha-MSH may affect some part of immune regulation separate from the immediate inflammatory response. Work continues to find what this process is.
Graph shows ear swelling due to contact dermatitis at 24 hours (left) and 2 weeks (right). Note that giving Ac-KPV-NH2 with the irritant is nearly as effective as giving alpha-MSH with the irritant at 24 hours. At 2 weeks, however, exposure to the stimulus without the peptides shows much less swelling with alpha-MSH compared to Ac-KPV-NH2.
Wound Healing
Wound healing is a complex body process. Scientists have identified three general phases: inflammatory, proliferative, and remodeling. Each phase has different cell types and chemical levels, creating a unique setting for possible treatments. Research shows that even though each wound healing stage has different skin cell subtypes, most express a melanocortin 1 receptor (MC1R) that binds alpha-melanocyte-stimulating hormone. Of course, this means these cell types also bind alpha-MSH versions like Ac-KPV-NH2 and KdPT.
Because these alpha-MSH derivatives keep some traits of alpha-MSH but lack others, they offer potential benefits in wound healing. For example, Ac-KPV-NH2 provides the anti-inflammatory effects of alpha-MSH but without the pigment-causing activity of its parent peptide. This makes Ac-KPV-NH2 a good option for improving wound healing while avoiding skin changes often linked to natural scar formation, which affects darker-skinned people more.
One reason Ac-KPV-NH2 is anti-inflammatory is that it takes part in the body’s natural immune response against two common skin germs. Research shows Ac-KPV-NH2 slows the growth of both Staphylococcus aureus and Candida albicans. These benefits happen at normal body levels, meaning Ac-KPV-NH2 could prevent infection in serious wounds like burns. This Ac-KPV-NH2 benefit contrasts with other anti-inflammatory drugs that actually weaken the body’s ability to fight infection. Thus, Ac-KPV-NH2 combines anti-inflammatory action with germ-fighting activity.
Ac-KPV-NH2 serves as a structural model in recent research aiming to copy the peptide’s anti-fungal effects in new treatments. The idea is that Ac-KPV-NH2’s 3D structure makes it an effective anti-fungal, and copying this could help create compounds with the same anti-fungal activity but different effects on other body processes.
Scar Formation
In line with Ac-KPV-NH2’s known benefits in the first stage of wound healing (inflammation), research has also looked at its role in the other two stages. It appears Ac-KPV-NH2 can reduce the chronic inflammation that leads to overgrown scars like keloids. This scarring has widespread macrophage entry, TNF activity, and high neutrophil levels. Giving alpha-MSH in this setting leads to smaller scars and a milder inflammatory response. Similar effects have been seen in other tissues like lung and heart. These findings raise hope that Ac-KPV-NH2 could help prevent scarring from certain chemotherapy drugs. This would not only cut cancer treatment side effects but could allow higher doses of these drugs and better cancer outcomes.
According to Dr. Didier Merlin, at least part of Ac-KPV-NH2’s benefit in reducing scar visibility comes from its ability to adjust collagen metabolism. Alpha-MSH and similar compounds block IL-8 release, which slows collagen type 1 production. This is key during the last wound healing phase, remodeling, as people prone to keloids and overgrown scarring have less MC1R mRNA on skin fibroblasts.
Ac-KPV-NH2 versus Alpha-MSH
While alpha-MSH is the stronger of the two, it has one serious drawback compared to Ac-KPV-NH2—it causes skin darkening. This side effect alone has discouraged more research into full alpha-MSH as an anti-inflammatory. Ac-KPV-NH2 is preferred because it keeps most anti-inflammatory traits of alpha-MSH without the side effects. Ac-KPV-NH2 is also very easy to make, giving it advantages in cost and handling.
Dr. Thomas Luger, a well-known skin doctor and expert in skin inflammatory diseases, has published widely on Ac-KPV-NH2. His work shows the peptide has strong anti-inflammatory effects with few bad outcomes.
It is also important to note that Ac-KPV-NH2’s anti-inflammatory effects seem to work through a different process than alpha-MSH. While alpha-MSH binds to specific melanocortin receptors, Ac-KPV-NH2 does not. Evidence comes from mouse studies where blocking MC3/4 receptors, which handle alpha-MSH’s anti-inflammatory effects, has no impact on Ac-KPV-NH2’s effects. Specifically, blocking these receptors does not stop the white blood cell movement effects caused by Ac-KPV-NH2.
Another appealing feature of Ac-KPV-NH2 is how easily it can be given. Animal studies show Ac-KPV-NH2 can be given by mouth, under the skin, or by injection (to the body or brain) without serious side effects. Recent similar research showed Ac-KPV-NH2 could be given through the skin with success. Being able to give the drug in multiple ways is not just convenient. Different methods affect how the peptide works and where its anti-inflammatory effects focus. The ability to change delivery lets scientists target different body areas for treatment.