Discovery of a Highly Potent and Selective Dual PROTAC Degrader of CDK12 and CDK13

Autor:	Jianzhang Yang, Yu Chang, Jean Ching-Yi Tien, Zhen Wang, Yang Zhou, Pujuan Zhang, Weixue Huang, Josh Vo, Ingrid J. Apel, Cynthia Wang, Victoria Zhixuan Zeng, Yunhui Cheng, Shuqin Li, George Xiaoju Wang, Arul M. Chinnaiyan, Ke Ding
Rok vydání:	2022
Předmět:	Proteomics Cell Line Tumor CDC2 Protein Kinase Proteolysis Drug Discovery Humans Molecular Medicine Triple Negative Breast Neoplasms Cyclin-Dependent Kinases
Zdroj:	Journal of Medicinal Chemistry. 65:11066-11083
ISSN:	1520-4804 0022-2623
DOI:	10.1021/acs.jmedchem.2c00384
Popis:	Selective degradation of the cyclin-dependent kinases 12 and 13 (CDK12/13) presents a novel therapeutic opportunity for triple-negative breast cancer (TNBC), but there is still a lack of dual CDK12/13 degraders. Here, we report the discovery of the first series of highly potent and selective dual CDK12/13 degraders by employing the proteolysis-targeting chimera (PROTAC) technology. The optimal compound
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::729f4d2ce8c183f7d15b5ab3aef4e7c9 https://doi.org/10.1021/acs.jmedchem.2c00384 Zobrazit plný text záznamu