CDK12 inhibitor E9 racemate

A clinical analog of THZ1 and a selective, covalent CDK12 inhibitor that is not susceptible to ABC transporter-mediated drug efflux; dose-dependently decreases phosphorylated and total RNAPII in THZ1R NB and lung cancer models, competed strongly with bio-THZ1 for binding to CDK12 at low nanomolar ranges, but not CDK7 (>1 uM); exerts its cytotoxic effects through covalent modification of cysteine 1039 of CDK12; shows more potent antiproliferative activity in THZ1R NB and lung cancer cells with IC50 ranging from 8 to 40 nM than ribociclib, palbociclib, and AZD5438.

References 1. Gao Y, et al. Cell Chem Biol. 2017 Dec 15. pii: S2451-9456(17)30424-5. View Related Products by Target Cyclin-dependent Kinase (CDK)