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Usage

Uses

Used in Pharmaceutical Industry:
THZ-531 is used as a CDK 12 and CDK 13 inhibitor for its ability to cause a loss of gene expression and concurrent loss of elongating and hyperphosphorylated RNA polymerase II. This unique mechanism of action has the potential to be applied in the development of new treatments for various diseases, including cancer and other genetic disorders.
Used in Cancer Research:
THZ-531 is used as a research tool for studying the role of CDK 12 and CDK 13 in cancer development and progression. By inhibiting these kinases, researchers can gain insights into the molecular pathways involved in tumor growth and identify potential therapeutic targets for cancer treatment.
Used in Drug Development:
THZ-531 is used as a lead compound in the development of new drugs targeting CDK 12 and CDK 13. Its covalent binding properties and unique mechanism of action make it an attractive candidate for further optimization and development into a potent and selective drug for various therapeutic applications.

Biological Activity

thz531 is a first-in-class cdk12 and cdk13 covalent inhibitor with ic50 values of 158 nm and 69 nm, respectively [1].complexes containing cdk12 and cdk13 regulate transcriptional elongation as well as processes, including mrna splicing and 3’-end rna processing. loss of cdk12 and cdk13, or of their cofactor cyclin k, impedes both pol ii processivity and rna processing [1].thz531 is an irreversible cdk12 and cdk13 covalent inhibitor. thz531 potently inhibited cdk12 and cdk13 with ic50 values of 158 nm and 69 nm, whereas inhibition of cdk7 and cdk9 was more than 50-fold weaker, with ic50s of 8.5 μm and 10.5 μm, respectively. in jurkat cells, thz531 irreversibly reduced cell proliferation with ic50 of 50 nm. thz531 induced apoptosis in a dose- and time-dependent way. thz531 also reduced pol ii c-terminal domain (ctd) ser2 phosphorylation, a mark of active transcriptional elongation, resulted in the loss of key super-enhancer-associated transcription factor genes and dna damage response (ddr) genes expression [1].1.zhang t, kwiatkowski n, olson cm, et al. covalent targeting of remote cysteine residues to develop cdk12 and cdk13 inhibitors. nat chem biol. 2016 oct;12(10):876-84.