Belew Mahder Dawit, Chen Jingrui, Cheng Zhaokang
Department of Pharmaceutical Sciences, Washington State University, 412 E. Spokane Falls Blvd., Spokane, WA 99202-2131, USA.
Department of Pharmaceutical Sciences, Washington State University, 412 E. Spokane Falls Blvd., Spokane, WA 99202-2131, USA.
Trends Mol Med. 2025 Feb;31(2):138-151. doi: 10.1016/j.molmed.2024.09.004. Epub 2024 Oct 15.
Cyclin-dependent kinase 7 (CDK7) regulates cell cycle and transcription, which are central for cancer progression. CDK7 inhibitors exhibit substantial anticancer activities in preclinical studies and are currently being evaluated in clinical trials. CDK7 is widely expressed in the body. However, the impact of CDK7 inhibition on normal tissues has received little attention. Here, we review the biological functions of CDK7, followed by its emerging roles in development, homeostasis and diseases. We discuss the regulatory mechanisms of CDK7 kinase activation and provide an overview of CDK7 substrates identified to date. Moreover, we highlight unanswered questions and propose key areas for future investigation. An advanced understanding of CDK7 will facilitate the pharmaceutical development of CDK7 inhibitors and help minimize undesirable adverse effects.
细胞周期蛋白依赖性激酶7(CDK7)调节细胞周期和转录,这对癌症进展至关重要。CDK7抑制剂在临床前研究中显示出显著的抗癌活性,目前正在临床试验中进行评估。CDK7在体内广泛表达。然而,CDK7抑制对正常组织的影响很少受到关注。在此,我们综述了CDK7的生物学功能,随后阐述其在发育、体内平衡和疾病中的新作用。我们讨论了CDK7激酶激活的调控机制,并概述了迄今为止已确定的CDK7底物。此外,我们强调了尚未解决的问题,并提出了未来研究的关键领域。对CDK7的深入了解将有助于CDK7抑制剂的药物研发,并有助于将不良副作用降至最低。