THZ 531

THZ 531 (THZ531) is a first-in-class, selective CDK12 and CDK13 covalent inhibitor with IC50 of 158 nM and 69 nM, respectively; 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; 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) ; 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.