CDK12 inhibitor E9 racemate 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 racemate 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 racemate 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 racemate exerts its cytotoxic effects through covalent modification of cysteine 1039 of CDK12.
CDK12 inhibitor E9 racemate 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.
