Bromodomain and extra-terminal domain proteins (BET proteins) are epigenetic reader proteins that have been implicated in regulating gene expression through binding to chromatin and interaction with transcription factors. These proteins are located in the nucleus and are responsible for recognizing acetylated lysine residues on histones, reading epigenetic messages, recruiting key transcription factors, and thereby regulating gene expression. BET proteins control the transcription of genes responsible for maladaptive effects in inflammation, cancer, and renal and cardiovascular diseases. Given the multifaceted role of BET proteins in the pathogenesis of various diseases, several small molecule inhibitors of BET proteins have been developed as potential therapeutic targets for treating different diseases in recent years. However, while many nonselective BET inhibitors are indicated for the treatment of cancer, a selective BET inhibitor, apabetalone, is the only oral BET inhibitor in phase III clinical trials for the treatment of cardiovascular diseases and others. Thus, this review aims to present and discuss the preclinical and clinical evidence for the beneficial effects and mechanism of action of apabetalone for treating various diseases.

中文翻译：

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Apabetalone (RVX-208)：一种潜在的表观遗传疗法，用于治疗心血管、肾脏、神经、病毒和癌症疾病

溴结构域和额外末端结构域蛋白（BET 蛋白）是表观遗传读取蛋白，它们通过与染色质结合以及与转录因子相互作用来调节基因表达。这些蛋白质位于细胞核中，负责识别组蛋白上的乙酰化赖氨酸残基、读取表观遗传信息、招募关键转录因子，从而调节基因表达。BET 蛋白控制负责炎症、癌症、肾脏和心血管疾病适应不良效应的基因的转录。鉴于BET蛋白在各种疾病发病机制中的多方面作用，近年来已开发出几种BET蛋白的小分子抑制剂作为治疗不同疾病的潜在治疗靶点。然而，虽然许多非选择性 BET 抑制剂适用于治疗癌症，但选择性 BET 抑制剂 apabetalone 是唯一处于治疗心血管疾病和其他疾病的 III 期临床试验中的口服 BET 抑制剂。因此，本综述旨在介绍和讨论 apabetalone 治疗各种疾病的有益效果和作用机制的临床前和临床证据。