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(E/Z)-THZ1 dihydrochloride

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Chemical Structure| 2095433-94-4 同义名 : THZ1 Dihydrochloride;THZ1 2HCl
CAS号 : 2095433-94-4
货号 : A303658
分子式 : C31H30Cl3N7O2
纯度 : 99%+
分子量 : 638.975
MDL号 : N/A
存储条件：

粉末 Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 : -
动物实验配方：

5% DMSO+45% PEG 300+water 4 mg/mL

生物活性
靶点

  • CDK7

    CDK7, IC50:3.2 nM
描述 CDK7, belonging to the CDK family, can form part of the TFIIH complex with Cyclin H/MAT1 and regulate RNA polymerase II transcription and DNA repair.[2] THZ1 is a highly selective inhibitor of CDK7 with IC50 value of 3.2nM (measured by THZ1 enzymatic activity). Treatment with THZ1≥250nM for 4h can completely inhibit the phosphorylation of the established intracellular RNAPII CTD, the substrate of CDK7, at Ser 5 and Ser 7 in Jurkat cells, with concurrent loss of Ser 2 phosphorylation. THZ1 on concentration of 250nM can reduced RNAPII occupancy genome wide at both promoters and gene bodies in while Flavopiridol reduced RNAPII density only across gene bodies. THZ1 showed broad-based activity with half-maximum inhibitory concentration (IC50) values less than 200nM against 598 cell lines, which have a strong enrichment of common expression of (proto-) oncogenic transcription factors involved in RNAPII-driven transcriptional regulation. Intravenous treatment of THZ1 10mg/kg once daily or twice days for 29 days exhibited efficacy in a human T-ALL cell-line KOPTK1 xenografted mouse model[1].
作用机制 THZ1 is a covalent CDK7 inhibitor which can target ATP-binding pocket of CDK7.[1]
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
Jurkat cells Cytotoxicity assay 72 h Cytotoxicity against human Jurkat cells assessed as cell viability after 72 hrs by resazurin assay, IC50=0.05 μM 26115571
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.56mL

0.31mL

0.16mL

7.83mL

1.56mL

0.78mL

15.65mL

3.13mL

1.56mL
参考文献

[1]Kwiatkowski N, Zhang T, et al. Targeting transcription regulation in cancer with a covalent CDK7 inhibitor. Nature. 2014 Jul 31;511(7511):616-20.

[2]Roskoski R Jr, et al. Cyclin-dependent protein kinase inhibitors including palbociclib as anticancer drugs. Pharmacol Res. 2016 May;107:249-275.

[3]Wang Y, Zhang T, et al. CDK7-dependent transcriptional addiction in triple-negative breast cancer. Cell. 2015;163(1):174-86.

[4]Chipumuro E, Marco E, et al. CDK7 inhibition suppresses super-enhancer-linked oncogenic transcription in MYCN-driven cancer. Cell. 2014;159(5):1126-1139.