CDK12 inhibitor E9 R-isomer is a clinical analog of THZ1 and a selective, covalent CDK12 inhibitor that is not susceptible to ABC transporter-mediated drug efflux.
CDK12 inhibitor E9 R-isomer is a clinical analog of THZ1 and a selective, covalent CDK12 inhibitor that is not susceptible to ABC transporter-mediated drug efflux.
CDK12 inhibitor E9 R-isomer 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).
CDK12 inhibitor E9 R-isomer exerts its cytotoxic effects through covalent modification of cysteine 1039 of CDK12.
CDK12 inhibitor E9 R-isomer 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.
