Abstract：
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.
摘要：
溴结构域和末端外(BET)蛋白具有与存在于组蛋白和非组蛋白中的乙酰化赖氨酸残基结合的能力。串联溴结构域的存在促进了这种结合。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BRD2、3、4和BRDT。BET蛋白是一类表观遗传学读写器,其调节参与癌症发病机理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)干扰BET蛋白与染色质的乙酰化赖氨酸残基的结合,从而导致几个基因转录的抑制，包括致癌转录因子。在这篇评论中，我们关注的是Bromodomain和外C端(BET)蛋白在癌症进展中的作用.此外，许多具有泛BET活性的小分子抑制剂已被证明，某些化合物目前正在接受临床评估。然而,很明显，本BET抑制剂的临床有效性受到限制，促进新技术的探索，以提高其临床结果和减轻不良副作用。因此，开发选择性BET-BD1和BD2抑制剂等策略，本综述还介绍了双重和作用BET，并试图涵盖正确建立设计分子进入BRD所需的化学。此外，这篇综述试图总结迄今为止的研究细节，并为副作用减少的BET抑制剂的未来发展提出了空间。可以得出结论，发现同种型选择性BET抑制剂可能是开发副作用可忽略不计的BET抑制剂的一种方法。
