THZ531 (THZ-531) is a first-in-class, selective CDK12 and CDK13 covalent inhibitor with IC50 of 158 nM and 69 nM, respectively.
THZ531) dispalys 50-fold selectivity over CDK7 and CDK9 (IC50 of 8.5 and 10.5 uM, respectively), and shows no appreciable inhibitory effect on ERK1.
THZ531) irreversiblely inhibits Jurkat cell proliferation with an IC50 of 50 nM, induces apoptosis in a dose- and time-dependent manner with low doses (<350 nM).
THZ531) selectively reduced Ser2 phosphorylation levels without appreciable effect on CTD pSer5/pSer7 levels, causes a loss of gene expression with concurrent loss of elongating and hyperphosphorylated RNA polymerase II, inhibits DDR and transcription factor gene expression.
