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.
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