Title: Melanin Concentrating Hormone Receptor Antagonists as Antiobesity Agents: From M2 to MCHR-1
VOLUME: 7 ISSUE: 15
Author(s):Mark D. McBriar
Affiliation:Department of Chemical Research, Schering-Plough Research Institute, 2015 Galloping Hill Road,Kenilworth, NJ 07033-1300, USA.
Keywords:Melanin-concentrating hormone, MCH, MCH R1, MCH R1 antagonist, obesity
Abstract: Melanin concentrating hormone (MCH) is a cyclic, nonadecapeptide expressed in the CNS of all vertebrates that regulates feeding behavior and energy homeostasis. The MCH-1 receptor (MCH-R1) has been identified as a key target in MCH regulation, as small molecule antagonists of MCH-R1 have demonstrated activity in vivo. Herein, we chronicle our efforts to optimize a hit identified via high throughput screening of our proprietary compound library. Several challenges such as selectivity over other receptors, toxicity of a potential metabolite and determining receptor occupancy via a medium throughput assay will be reviewed.
