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转录相关激酶的化学抑制剂。

Chemical inhibitors of transcription-associated kinases.

机构信息

Dept. of Biochemistry, University of Colorado, Boulder, CO, USA.

Dept. of Biochemistry, University of Colorado, Boulder, CO, USA.

出版信息

Curr Opin Chem Biol. 2022 Oct;70:102186. doi: 10.1016/j.cbpa.2022.102186. Epub 2022 Aug 1.

Abstract

Transcription by RNA polymerase II (pol II) is regulated by kinases. In recent years, many selective and potent inhibitors of pol II transcription-associated kinases have been developed, and these molecules have advanced understanding of kinase function in mammalian cells. Here, we focus on chemical inhibitors of the transcription-associated kinases CDK7, CDK8, CDK9, CDK12, CDK13, and CDK19. We provide a brief overview of the function of these kinases and common activation mechanisms. We then highlight the advantages of kinase inhibitors compared with other basic research methods, and describe the caveats associated with non-selective compounds (e.g. flavopiridol). We conclude with strategies and recommendations for implementation of chemical inhibitors for experimental analysis of transcription-associated kinases.

摘要

RNA 聚合酶 II(pol II)的转录受激酶调控。近年来,许多针对 pol II 转录相关激酶的选择性和有效抑制剂已被开发出来,这些分子促进了对哺乳动物细胞中激酶功能的理解。在这里,我们重点介绍转录相关激酶 CDK7、CDK8、CDK9、CDK12、CDK13 和 CDK19 的化学抑制剂。我们简要概述了这些激酶的功能和常见的激活机制。然后,我们强调了激酶抑制剂与其他基础研究方法相比的优势,并描述了非选择性化合物(如 flavopiridol)相关的注意事项。最后,我们提出了用于实验分析转录相关激酶的化学抑制剂的实施策略和建议。

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