THZ1 is an irreversible, covalent inhibitor (dual ATP-site and allosteric covalent binding) of CDK7 (IC50 = 15.6nM @ 20min and 3.2nM @ 180 min). It displayed broad based antiproliferative activity with IC50’s of less than 200nM against 53% of the 1000 cancer cell lines it was tested against....
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THZ1 is an irreversible, covalent inhibitor (dual ATP-site and allosteric covalent binding) of CDK7 (IC50 = 15.6nM @ 20min and 3.2nM @ 180 min). It displayed broad based antiproliferative activity with IC50’s of less than 200nM against 53% of the 1000 cancer cell lines it was tested against. THZ1 disrupts transcription of several proteins including RUNX1, TAL1, and GATA3. It suppresses oncogenic transcription of MYCN-driven cancers. THZ1 decreases STAT3 chromatin binding and expression of target genes such as MYC, PIM1, and others in peripheral T-Cell lymphoma cells with the Y640F STAT3 mutation. Addition of THZ1 to targeted cancer therapy increases cell death and hinders the development of drug-resistant cell populations in cellular and in vitro cancer models
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