Melanin concentrating hormone receptor antagonists as antiobesity agents: from M2 to MCHR-1.
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.
McBriar
Mark D
MD
Department of Chemical Research, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033-1300, USA. mark.mcbriar@spcorp.com
D000818:Animals; D004353:Drug Evaluation, Preclinical; D006801:Humans; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D011979:Receptors, Pituitary Hormone / Q000037:antagonists & inhibitors* / Q000145:classification / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013997:Time Factors
D011979:Receptors, Pituitary Hormone; C092274:melanin-concentrating hormone receptor