溴结构域和外终端（BET）蛋白具有与组蛋白和非组蛋白蛋白中存在的乙酰化赖氨酸残基结合的能力。这种结合是通过串联的溴结构域的存在来促进的。BET蛋白的调节作用延伸到染色质动力学、细胞过程和疾病进展。BET家族包括BRD 2、3、4和BRDT。BET蛋白是一类表观遗传读取蛋白，调节着与癌症发病机制相关的多种基因的转录活性。因此，靶向BET蛋白已被确定为治疗癌症的潜在有效方法。已知BET抑制剂（BETis）能够干扰BET蛋白与染色质乙酰化赖氨酸残基的结合，从而抑制多个基因的转录，包括致癌转录因子。在这篇综述中，我们专注于溴结构域和额外C-末端（BET）蛋白在癌症进展中的作用。此外，已经记录了许多具有广谱BET活性的小分子抑制剂，并且目前有一些化合物正在进行临床评估。然而，目前的BET抑制剂的临床有效性受到限制，因此需要探索新的技术来提高其临床效果并减少不良副作用。因此，本综述也介绍了开发选择性BET-BD1和BD2抑制剂、双重和作用于BET蛋白的策略，并尝试概述了设计分子进入BRD所需的化学过程。此外，本综述试图总结迄今为止的研究细节，并提出降低副作用的BET抑制剂未来发展的空间。可以得出结论，发现亚型选择性的BET抑制剂可能是未来发展BET抑制剂以减少副作用的一种方式。Copyright © 2023 Elsevier Inc. All rights reserved.

Bromodomain and extraterminal (BET) proteins have the ability to bind to acetylated lysine residues present in both histones and non-histone proteins. This binding is facilitated by the presence of tandem bromodomains. The regulatory role of BET proteins extends to chromatin dynamics, cellular processes, and disease progression. The BET family comprises of BRD 2, 3, 4 and BRDT. The BET proteins are a class of epigenetic readers that regulate the transcriptional activity of a multitude of genes that are involved in the pathogenesis of cancer. Thus, targeting BET proteins has been identified as a potentially efficacious approach for the treatment of cancer. BET inhibitors (BETis) are known to interfere with the binding of BET proteins to acetylated lysine residues of chromatin, thereby leading to the suppression of transcription of several genes, including oncogenic transcription factors. Here in this review, we focus on role of Bromodomain and extra C-terminal (BET) proteins in cancer progression. Furthermore, numerous small-molecule inhibitors with pan-BET activity have been documented, with certain compounds currently undergoing clinical assessment. However, it is apparent that the clinical effectiveness of the present BET inhibitors is restricted, prompting the exploration of novel technologies to enhance their clinical outcomes and mitigate undesired adverse effects. Thus, strategies like development of selective BET-BD1, & BD2 inhibitors, dual and acting BET are also presented in this review and attempts to cover the chemistry needed for proper establishment of designed molecules into BRD have been made. Moreover, the review attempts to summarize the details of research till date and proposes a space for future development of BET inhibitor with diminished side effects. It can be concluded that discovery of isoform selective BET inhibitors can be a way forward in order to develop BET inhibitors with negligible side effects.Copyright © 2023 Elsevier Inc. All rights reserved.