CDK12: a potential therapeutic target in cancer
Date
2020
Authors
Emadi, F.
Teo, T.
Rahaman, M.H.
Wang, S.
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Journal article
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Drug Discovery Today, 2020; 25(12):2257-2267
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Fatemeh Emadi, Theodosia Teo, Muhammed H. Rahaman and Shudong Wang
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Abstract
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.
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© 2020 Elsevier Ltd. All rights reserved.