THZ1 2HCl

THZ1 2HCl (CAS No.: 2095433-94-4) is a synthetic small molecule classified as a covalent, selective allosteric inhibitor of cyclin-dependent kinase 7 (CDK7); CDK7 is a core component of the TFIIH complex involved in transcription initiation and regulates cell cycle progression through the CDK-activating kinase (CAK) module. THZ1 2HCl achieves target selectivity by covalently binding to a cysteine residue located outside the conventional kinase domain, thereby inhibiting CDK7-dependent RNA polymerase II phosphorylation events and reducing activation-loop phosphorylation levels of its partner cell cycle kinases, overall modulating transcription- and cell cycle-related signaling axes. It is suitable for mechanism studies and target discovery oriented toward cancer biology. In biochemical assays, this compound shows nanomolar potency against CDK7, with a reported IC50 of approximately 3.2 nM; in cellular models, it exhibits antiproliferative activity against various tumor-derived cells, with activity commonly ranging from low nanomolar to submicromolar levels, depending on cellular context and experimental conditions. As a research tool compound, THZ1 2HCl is commonly used for in vitro kinase inhibition and target occupancy evaluation, transcriptional and epigenomic analyses, pathway elucidation, and high-content or combination screening, and is also used in animal models to investigate CDK7-related signaling and transcriptional dependence; the concentrations or doses used in experiments typically depend on the specific experimental design and research objectives. Its main application areas include chemical biology, transcriptional regulation research, and target validation in oncology. This product is for laboratory research use only and is not intended for diagnostic or other non-research uses.