Setmelanotide
Setmelanotide is a peptide drug and investigational anti-obesity medication which acts as a selective agonist of the MC4 receptor. Its peptide sequence is Ac-Arg-Cys-D-Ala-His-D-Phe-Arg-Trp-Cys-NH2. It was first discovered at Ipsen and is being developed by Rhythm Pharmaceuticals for the treatment of obesity and diabetes. In addition, Rhythm Pharmaceuticals is conducting trials of setmelanotide for the treatment of Prader–Willi syndrome, a genetic disorder which includes MC4 receptor deficiency and associated symptoms such as excessive appetite and obesity. As of December 2014, the drug is in phase II clinical trials for obesity and PWS. So far, preliminary data has shown no benefit of Setmelanotide in Prader-Willi syndrome.
Setmelanotide binds to and activates MC4 receptors in the paraventricular nucleus of the hypothalamus and in the lateral hypothalamic area, areas involved in the regulation of appetite, and this action is thought to underlie its appetite suppressant effects. In addition to reducing appetite, setmelanotide increases resting energy expenditure in both obese animals and humans. Importantly, unlike certain other MC4 receptor agonists, such as LY-2112688, setmelanotide has not been found to produce increases in heart rate or blood pressure.
Setmelanotide has been reported to possess the following activity profile : MC4 > MC3 ≈ MC1 > MC5 ≟ MC2.
