CDK12: a potential therapeutic target in cancer

•The wide functionality of CDK12 in a cell-specific manner.•Rationale for using CDK12 as a biomarker and therapeutic target.•Structural dissection of CDK12 associated with its biological roles.•Challenges and strategies to develop potent and selective CDK12 inhibitors. Cyclin-dependent kinase (CDK)...

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Bibliographic Details
Published in:Drug discovery today 2020-12, Vol.25 (12), p.2257-2267
Main Authors: Emadi, Fatemeh, Teo, Theodosia, Rahaman, Muhammed H., Wang, Shudong
Format: Article
Language:English
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Summary:•The wide functionality of CDK12 in a cell-specific manner.•Rationale for using CDK12 as a biomarker and therapeutic target.•Structural dissection of CDK12 associated with its biological roles.•Challenges and strategies to develop potent and selective CDK12 inhibitors. Cyclin-dependent kinase (CDK) 12 engages in diversified biological functions, from transcription, post-transcriptional modification, cell cycle, and translation to cellular proliferation. Moreover, it regulates the expression of cancer-related genes involved in DNA damage response (DDR) and replication, which are responsible for maintaining genomic stability. CDK12 emerges as an oncogene or tumor suppressor in different cellular contexts, where its dysregulation results in tumorigenesis. Current CDK12 inhibitors are nonselective, which impedes the process of pharmacological target validation and drug development. Herein, we discuss the latest understanding of the biological roles of CDK12 in cancers and provide molecular analyses of CDK12 inhibitors to guide the rational design of selective inhibitors.
ISSN:1359-6446
1878-5832
DOI:10.1016/j.drudis.2020.09.035