Compound 7f (Jinan University)

Compound 7f is a highly potent and selective dual proteolysis-targeting chimera (PROTAC) degrader of cyclin-dependent kinase 12 (CDK12) and cyclin-dependent kinase 13 (CDK13). Developed through a collaboration between Jinan University, the University of Michigan, and the Chinese Academy of Sciences, it was designed by linking a CDK12/13 inhibitor to a cereblon (CRBN) E3 ligase ligand via a linker containing a -CH2-NH- moiety. The compound effectively degrades both kinases with DC50 values of 2.2 nM and 2.1 nM, respectively, in MDA-MB-231 breast cancer cells. By degrading these targets, Compound 7f suppresses the expression of DNA damage response (DDR) genes and markedly inhibits the proliferation of multiple triple-negative breast cancer (TNBC) cell lines, including MFM223. Although it is a powerful research tool commercially available as PROTAC CDK12/13 Degrader-1, it currently lacks oral bioavailability and has not been approved for clinical use.

Other names

CDK12/13 PROTAC degrader 7f