School of Pharmacy, Lebanese American University, P.O. Box 36, Byblos, Lebanon.
Drug Discovery and Development, University of South Australia Cancer Research Institute, Adelaide, SA 5000, Australia.
J Med Chem. 2020 Jul 23;63(14):7458-7474. doi: 10.1021/acs.jmedchem.9b01985. Epub 2020 Mar 19.
Cyclin-dependent kinase (CDK) 7 has a unique functional repertoire by virtue of its dual role in transcription and cell cycle progression. Whereas CDK7 is ubiquitously expressed in various types of cancer, its downregulation leads to reduced cell proliferation. Importantly, it is now agreed that targeting transcription selectively limits the synthesis of mRNAs involved in tumor growth without causing an outage of transcription of housekeeping genes. Thus, CDK7 has been considered as a viable therapeutic target in cancer. Indeed, the development of CDK7 inhibitors has gained huge momentum with two molecules, CT7001 and SY-1365, currently under clinical development. Herein, we discuss the latest understanding of the role of CDK7 in cancer cells and provide an overview of the pharmacophores of CDK7 inhibitors, their efficacy in various cancer models, and their clinical development.
周期蛋白依赖性激酶 (CDK) 7 因其在转录和细胞周期进展中的双重作用而具有独特的功能。虽然 CDK7 在各种类型的癌症中广泛表达，但它的下调会导致细胞增殖减少。重要的是，现在人们已经认识到，选择性地靶向转录可以限制与肿瘤生长相关的 mRNA 的合成，而不会导致管家基因的转录中断。因此，CDK7 已被认为是癌症治疗的一个可行靶点。事实上，随着两种分子 CT7001 和 SY-1365 的临床开发，CDK7 抑制剂的开发已经取得了巨大的进展。本文讨论了 CDK7 在癌细胞中的作用的最新认识，并概述了 CDK7 抑制剂的药效团、它们在各种癌症模型中的疗效及其临床开发。
