CDK抑制剂;CDK Inhibitors;;InformationTHZ531 THZ531 is a selective covalent inhibitor of CDK12 and CDK13 with IC50 values of 158 and 69 nM, respectively.TargetsCDK13 ; CDK12 69 nM; 158 nMIn vitroTHZ531 treatment leads to a dramatic and irreversible decrease in Jurkat cell proliferation with an IC50 of 50 nM. THZ531 induces apoptosis in a dose- and time-dependent manner with low doses (<350 nM) leading to slow onset of apoptosis over several cell doublings, while doses exceeding 350 nM induce rapid apoptosis which may result from a combination of on- and off- target effects. THZ531 reduces Pol II CTD Ser2 phosphorylation (pSer2) in a concentration-dependent manner.
参考文献:
1. Zhang T, et al. Covalent targeting of remote cysteine residues to develop CDK12 and CDK13 inhibitors. Nat Chem Biol. 2016 Oct;12(10):876-84.