Document Report Card

ID: ALA2176866

Journal: J Med Chem

Title: Progress in the development and application of small molecule inhibitors of bromodomain-acetyl-lysine interactions.

Authors: Hewings DS, Rooney TP, Jennings LE, Hay DA, Schofield CJ, Brennan PE, Knapp S, Conway SJ.

Abstract: Bromodomains, protein modules that recognize and bind to acetylated lysine, are emerging as important components of cellular machinery. These acetyl-lysine (KAc) "reader" domains are part of the write-read-erase concept that has been linked with the transfer of epigenetic information. By reading KAc marks on histones, bromodomains mediate protein-protein interactions between a diverse array of partners. There has been intense activity in developing potent and selective small molecule probes that disrupt the interaction between a given bromodomain and KAc. Rapid success has been achieved with the BET family of bromodomains, and a number of potent and selective probes have been reported. These compounds have enabled linking of the BET bromodomains with diseases, including cancer and inflammation, suggesting that bromodomains are druggable targets. Herein, we review the biology of the bromodomains and discuss the SAR for the existing small molecule probes. The biology that has been enabled by these compounds is summarized.

CiteXplore: 22924434

DOI: 10.1021/jm300915b