Document Report Card

ID: ALA3286156

Journal: J Med Chem

Title: A fragment-based approach to identifying S-adenosyl-l-methionine -competitive inhibitors of catechol O-methyl transferase (COMT).

Authors: Lanier M, Ambrus G, Cole DC, Davenport R, Ellery J, Fosbeary R, Jennings AJ, Kadotani A, Kamada Y, Kamran R, Matsumoto S, Mizukami A, Okubo S, Okada K, Saikatendu K, Walsh L, Wu H, Hixon MS.

Abstract: Catechol O-methyl transferase belongs to the diverse family of S-adenosyl-l-methionine transferases. It is a target involved in the treatment of Parkinson's disease. Here we present a fragment-based screening approach to discover noncatechol derived COMT inhibitors which bind at the SAM binding pocket. We describe the identification and characterization of a series of highly ligand efficient SAM competitive bisaryl fragments (LE = 0.33-0.58). We also present the first SAM-competitive small-molecule COMT co-complex crystal structure.

CiteXplore: 24847974

DOI: 10.1021/jm500475k