Setmelanotide

Setmelanotide (INN, USAN) (code name RM-493, formerly BIM-22493, IRC-022493) 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(1)-D-Ala-His-D-Phe-Arg-Trp-Cys(1)-NH2. It is being researched 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 (PWS), 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.

Contents

• Pws clinical trial update setmelanotide
• Rhythm pharmaceuticals setmelanotide for the treatment of rare forms of monogenic obesity
• References

Setmelanotide binds to and activates MC₄ receptors in the paraventricular nucleus (PVN) of the hypothalamus and in the lateral hypothalamic area (LHA), 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 (cAMP, EC₅₀): MC₄ (0.27 nM) > MC₃ (5.3 nM) ≈ MC₁ (5.8 nM) > MC₅ (1600 nM) ≟ MC₂ (>1000 nM). (19.6-fold selectivity for MC₄ over MC₃, the second target of highest activity.)