Small Molecule Bromodomain Inhibitors

摘要: Bromodomains are modulators of protein–protein interactions essential for epigenetic mechanisms transcriptional control. The recent disclosure potent, selective, small molecule inhibitors the BET bromodomain subfamily and their profound in vivo activity several disease models suggests that druggable genome should be extended to include this epi–reader target class. This chapter reviews progress inhibitor drug discovery. role reader proteins gene regulation concept histone code introduced. therapeutic potential modulation oncology, inflammation, metabolic infectious is summarized. Methods lead identification including use phenotypic–, cell mechanistic–, biochemical– fragment–based screens described, as selectivity considerations emerging class. Difficulties exploring class also highlighted. Bromodomain chemical tractability discussed using published examples, where SAR X–ray crystal structures exemplify how potency can achieved.