期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 240, 期 -, 页码 -出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2022.114603
关键词
CDK12; Inhibitors; Drug combination; Cancer
资金
- Sichuan Science and Technology Program [2019YFS0003]
- National Natural Science Foundation of China [82073318, 81903502]
- National Major Scientific and Technological Special Project for Significant New Drugs Development [2018ZX09201018-021]
- Natural Science Foundation of Sichuan Prov- ince [2022NSFSC1365]
- Health Commission of Sichuan Province [21PJ149]
- Xinglin Foundation of Chengdu University of TCM [YYZX2021043]
CDK12 is a crucial kinase involved in various biological processes and associated with different types of cancer. Development of CDK12 inhibitors has faced challenges due to the similarity with CDK13, however, recent studies have made progress in this field and shed light on the structure-activity relationships for further development.
CDK12 is a cyclin-dependent kinase that plays critical roles in DNA replication, transcription, mRNA splicing, and DNA damage repair. CDK12 genomic changes, including mutation, amplification, deletion, and fusion, lead to various cancers, such as colorectal cancer, gastric cancer, and ovarian cancer. An increasing number of CDK12 inhibitors have been reported since CDK12 was identified as a biomarker and cancer therapeutic target. A major challenge lies in that CDK12 and CDK13 share highly similar sequences, which leads to great difficulties in the development of highly selective CDK12 inhibitors. In recent years, great efforts were made in developing selective CDK12 blockers. Techniques including PROTAC and molecular glue degraders were also applied to facilitate their development. Also, the drug combination strategy of CDK12 small molecule inhibitors were studied. This review discusses the latest studies on CDK12 inhibitors and analyzes their structure-activity relationships, shedding light on their further development.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据