THZ 531

SKU: orb1225958

Description

THZ 531 (THZ531) is a first-in-class, selective CDK12 and CDK13 covalent inhibitor with IC50 of 158 nM and 69 nM, respectively; dispalys 50-fold selectivity over CDK7 and CDK9 (IC50 of 8.5 and 10.5 uM, respectively), and shows no appreciable inhibitory effect on ERK1; irreversiblely inhibits Jurkat cell proliferation with an IC50 of 50 nM, induces apoptosis in a dose- and time-dependent manner with low doses (<350 nM); selectively reduced Ser2 phosphorylation levels without appreciable effect on CTD pSer5/pSer7 levels, causes a loss of gene expression with concurrent loss of elongating and hyperphosphorylated RNA polymerase II, inhibits DDR and transcription factor gene expression.

Key Properties

• CAS Number: 1702809-17-3
• MW: 558.083
• Purity: >98% (HPLC)
• Formula: C₃₀H₃₂ClN₇O₂
• SMILES: O=C(NC1=CC=C(C(N2C[C@H](NC3=NC=C(Cl)C(C4=CNC5=C4C=CC=C5)=N3)CCC2)=O)C=C1)/C=C/CN(C)C
• Target: CDK
• Solubility: DMSO: Soluble （ < 1 mg/ml refers to the product slightly soluble or insoluble )

Bioactivity

• In Vitro:
  The results from Kinase assays demonstrate that THZ531 potently inhibits CDK12 and CDK13 with IC50s of 158 nM and 69 nM, respectively; whereas inhibition of CDK7 and CDK9 is more than 50-fold weaker with IC50s of 8.5 and 10.5 μM, respectively. THZ531 treatment leads to a dramatic and irreversible decrease in Jurkat cell proliferation with an IC50 of 50 nM. FACS cell cycle analysis following treatment with escalating doses of THZ531 displays a dose and time-dependent increase in the number of cells exhibiting sub-G1 content. At 50 nM THZ531, no increase in the percentage of apoptotic cells is observed over DMSO control for the time course of the experiment. Higher doses of THZ531 leads to pronounced Annexin V signal with 30 to 40% annexin V-positively stained cells by 72 hrs. A dramatic reduction in elongating Pol II following THZ531 treatment is also observed.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

THZ531

Quick Database Links

Gene Symbol

CDK