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ID: ALA2146433

Journal: Bioorg Med Chem Lett

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

Authors: Högberg T, Frimurer TM, Sasmal PK.

Abstract: 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 ∼2000 diverse MCHR1 and ∼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.

CiteXplore: 22954736

DOI: 10.1016/j.bmcl.2012.08.025