Name: THZ531
Price: 292.00 USD

- Overview
  - Please contact us at for specific academic pricing.
    
    Background
    
    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].
- Properties
  - Alternative Name
    
    (R,E)-N-(4-(3-((5-chloro-4-(1H-indol-3-yl)pyrimidin-2-yl)amino)piperidine-1-carbonyl)phenyl)-4-(dimethylamino)but-2-enamide
    
    CAS Number
    
    1702809-17-3
    
    Molecular Formula
    
    C30H32ClN7O2
    
    Molecular Weight
    
    558.07
    
    Appearance
    
    A solid
    
    Purity
    
    99.81%
    
    Solubility
    
    ≥55.8 mg/mL in DMSO; insoluble in H2O; ≥4.9 mg/mL in EtOH
    
    Storage
    
    Store at -20°C
    
    * For Research Use Only
- Reference
  - 1. Peuget S, Zhu J, et al. "Thermal proteome profiling identifies oxidative-dependent inhibition of the transcription of major oncogenes as a new therapeutic mechanism for select anticancer compounds." Cancer Res. 2020;canres.2069.2019. PMID:32019870
    2. Wang C, Vegna S, et al. "Inducing and exploiting vulnerabilities for the treatment of liver cancer." Nature. 2019 Oct 2. PMID:31578521
    3. Wang C, Wang H, et al. "CDK12 inhibition mediates DNA damage and is synergistic with sorafenib treatment in hepatocellular carcinoma." Gut. 2019 Sep 13. pii: gutjnl-2019-318506. PMID:31519701

THZ531

THZ531

Background

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