Cyclin-dependent kinase 9 (CDK9), which regulates transcriptional elongation, is an attractive therapeutic target for many cancers, especially for cancers driven by transcriptional dysregulation. In particular, CDK9 promotes RNA polymerase II pause/release, a rate-limiting step in normal transcriptional regulation that is frequently dysregulated in cancers. Emerging evidence indicates that selective CDK9 inhibition or degradation may provide a therapeutic benefit against certain cancers. Indeed, the development of CDK9 modulators (inhibitors and degraders) has attracted great attention, with several molecules currently under clinical development. This review provides an overview of recent advances in CDK9 modulators in general, with special emphasis on compounds under clinical evaluation and new emerging strategies, such as proteolysis targeting chimeras (PROTACs).

中文翻译：

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CDK9抑制剂的生物学和药物化学的最新进展：更新。

调节转录伸长的细胞周期蛋白依赖性激酶9（CDK9）是许多癌症（尤其是转录失调驱动的癌症）有吸引力的治疗靶标。特别地，CDK9促进RNA聚合酶II的暂停/释放，这是正常转录调节中的一个限速步骤，在癌症中经常失调。新兴证据表明，选择性CDK9抑制或降解可能会提供针对某些癌症的治疗益处。实际上，CDK9调节剂（抑制剂和降解剂）的开发引起了极大的关注，目前有几种分子正在临床开发中。这篇综述概述了CDK9调节剂的最新进展，特别着重于临床评估和新兴战略中的化合物，