Dysfunction of the bromo and extra terminal domain (BET) family proteins is associated with many human diseases, therefore the BET family proteins have been considered as promising targets for drug development. Numerous small molecular compounds targeting the N-terminal two tandem bromodomains BD1 and BD2 of the BET family proteins have been reported, and a number of them have been advanced into clinical trials. Most of the BET inhibitors entered clinical trials are pan-BET inhibitors which show poor selectivity among BET members and bind to the BD1 and BD2 of the BET family proteins with comparable binding affinities. In order to elucidate the distinct functions of BD1s and BD2s, many BD1 and BD2 selective BET inhibitors have also been developed. In this review, we summarized the recent progress in the development of BD1 and BD2 selective BET inhibitors, and provided the perspectives for future studies of BET inhibitors.

溴和额外末端结构域 (BET) 家族蛋白的功能障碍与许多人类疾病有关，因此 BET 家族蛋白被认为是药物开发的有希望的目标。已经报道了许多针对 BET 家族蛋白的 N 端两个串联溴结构域 BD1 和 BD2 的小分子化合物，其中一些已进入临床试验。大多数进入临床试验的 BET 抑制剂是泛 BET 抑制剂，它们在 BET 成员中显示出较差的选择性，并以相当的结合亲和力与 BET 家族蛋白的 BD1 和 BD2 结合。为了阐明 BD1s 和 BD2s 的不同功能，还开发了许多 BD1 和 BD2 选择性 BET 抑制剂。在本次审查中，