THZ1

SKU: orb1303940

Description

THZ1 is a potent and selective covalent CDK7 inhibitor with an IC50 of 3.2 nM. Its mechanism involves targeting a specific cysteine residue, ensuring high selectivity. This compound is widely used in vitro and in vivo for cancer research, particularly in studies of transcriptional regulation and cell cycle progression.

Research Area

Cell Biology

Key Properties

• CAS Number: 1604810-83-4
• MW: 566.05
• Purity: 99.27% (May vary between batches)
• Formula: C₃₁H₂₈ClN₇O₂
• SMILES: CN(C)C\C=C\C(=O)Nc1ccc(cc1)C(=O)Nc1cccc(Nc2ncc(Cl)c(n2)-c2c[nH]c3ccccc23)c1
• Target: CDK
• Solubility: Ethanol:< 1 mg/mL (insoluble or slightly soluble);DMSO:250 mg/mL (441.66 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (3.53 mM)

Bioactivity

• Target IC50:
  CDK7:3.2 nM
• In Vivo:
  THZ1 reduces the proliferation of KOPTK1 T-ALL cells in a human xenograft mouse model. THZ1 is well tolerated at 10 mg/kg with no observable body weight loss or behavioural changes, suggesting that it causes no overt toxicity in the animals.
• In Vitro:
  THZ1 uses a unique mechanism, combining ATP-site and allosteric covalent binding, as a means of attaining potency and selectivity for CDK7. THZ1 irreversibly inhibits RNAPII CTD phosphorylation by covalently targeting a unique cysteine located outside the kinase domain of CDK7. THZ1, but not THZ1-R, completely inhibits the phosphorylation of the established intracellular CDK7 substrate RNAPII CTD at Ser 5 and Ser 7, with concurrent loss of Ser 2 phosphorylation at 250 nM in Jurkat cells. THZ1 exhibits strong antiproliferative effects across a broad range of cancer cell lines from various cancer types. In Jurkat cells, low-dose THZ1 has a profound effect on a small subset of genes, including the key regulator RUNX1, thus contributing to subsequent loss of the greater gene expression program and cell death. THZ1 causes defects in Pol II(polymerase II) phosphorylation, co-transcriptional capping, promoter proximal pausing, and productive elongation.
• Cell Research:
  Cells are treated with THZ1, THZ1-R or dimethylsulphoxide (DMSO) for 0-6 h to assess the effect of time on the THZ1-mediated inhibition of RNAPII CTD phosphorylation. For subsequent experiments cells are treated with compounds for 4 h as determined by the time-course experiment described earlier, unless otherwise noted. For inhibitor washout experiments, cells are treated with THZ1, THZ1-R or DMSO for 4 h. Medium containing inhibitors is subsequently removed to effectively 'washout' the compound and the cells are allowed to grow in the absence of inhibitor. For each experiment, lysates are probed for RNAPII CTD phosphorylation and other specified proteins.(Only for Reference)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

THZ 1, THZ1, THZ-1, THZ1 2HCl, CDK7 inhibitor, CDK7, CDK

Compound Identifiers

PubChem CID

73602827