Disrupting Acetyl-Lysine Recognition: Progress in the Development of Bromodomain Inhibitors

作者：F. Anthony Romero, Alexander M. Taylor, Terry D. Crawford, Vickie Tsui, Alexandre Côté, Steven Magnuson · 发表于：Journal of Medicinal Chemistry · 年份：2015 · DOI：10.1021/acs.jmedchem.5b01514 · 被引用次数：190 · 研究领域：Protein Degradation and Inhibitors、Multiple Myeloma Research and Treatments、Peptidase Inhibition and Analysis

Bromodomains, small protein modules that recognize acetylated lysine on histones, play a significant role in the epigenome, where they function as "readers" that ultimately determine the functional outcome of the post-translational modification. Because the initial discovery of selective BET inhibitors have helped define the role of that protein family in oncology and inflammation, BET bromodomains have continued to garner the most attention of any other bromodomain. More recently, non-BET bromodomain inhibitors that are potent and selective have been disclosed for ATAD2, CBP, BRD7/9, BRPF, BRPF/TRIM24, CECR2, SMARCA4, and BAZ2A/B. Such novel inhibitors can be used to probe the physiological function of these non-BET bromodomains and further understanding of their role in certain disease states. Here, we provide an update to the progress in identifying selective bromodomain inhibitors and their use as biological tools, as well as our perspective on the field.