Research Progress of Anticancer Drugs Targeting CDK12

Overview

Journal RSC Med Chem

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2023 Sep 21

PMID 37731700

Authors

Zhijia Yan

Yongli Du

Haibin Zhang

Yong Zheng

Huiting Lv

Ning Dong

Fang He

Affiliations

Soon will be listed here.

Abstract

Cyclin-dependent kinase 12 (CDK12) is a transcription-associated CDK that plays key roles in transcription, translation, mRNA splicing, the cell cycle, and DNA damage repair. Research has identified that high expression of CDK12 in organs such as the breast, stomach, and uterus can lead to HER2-positive breast cancer, gastric cancer and cervical cancer. Inhibiting high expression of CDK12 suppresses tumor growth and proliferation, suggesting that it is both a biomarker for cancer and a potential target for cancer therapy. CDK12 inhibitors can competitively bind the CDK12 hydrophobic pocket with ATP to avoid CDK12 phosphorylation, blocking subsequent signaling pathways. The development of CDK12 inhibitors is challenging due to the high homology of CDK12 with other CDKs. This review summarizes the research progress of CDK12 inhibitors, their mechanism of action and the structure-activity relationship, providing new insights into the design of CDK12 selective inhibitors.

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