Melanin concentrating hormone receptor 1 (MCHR1) antagonists-Still a viable approach for obesity treatment?

作者：Hogberg Thomas^*; Frimurer Thomas M; Sasmal Pradip K

来源：Bioorganic & Medicinal Chemistry Letters, 2012, 22(19): 6039-6047.

DOI：10.1016/j.bmcl.2012.08.025

• Melanin concentrating hormone (MCH)
• MCHR1 antagonists
• Chemometric analysis
• GPCR structures
• hERG
• Obesity

Obesity is a global epidemic associated with multiple severe diseases. Several pharmacotherapies have been investigated including the melanin concentrating hormone (MCH) and its receptor 1. The development of MCHR1 antagonists are described with a specific perspective on different chemotypes investigated in efforts to overcome hERG liabilities while having orally active, potent and selective compounds with sufficient brain penetration. A chemometric comparison of similar to 2000 diverse MCHR1 and similar to 1000 diverse hERG ligands underline the structural similarities. A binding pocket analysis of a MCHR1 model and recent X-ray structures of GPCRs invoked in selectivity issues indicate a way to support future drug design.

• 出版日期2012-10-1