|N-(3-((5-氯-4-(1H-吲哚-3-基)嘧啶-2-基)氨基)苯基)-4-(4-(二甲氨基)丁-2-烯酰胺基)苯甲酰胺二盐酸盐|CsnPharm

CAS No.: 2095433-94-4

N-(3-((5-Chloro-4-(1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)-4-(4-(dimethylamino)but-2-enamido)benzamide dihydrochloride Catalog No. CSN19264

Synonyms: THZ1 Dihydrochloride

THZ1 2HCl is a Cdk7 inhibitor (IC50s = 3.2-15.6 nM in vitro) that selectively targets a remote cysteine residue located outside of the classic kinase domain. THZ1 2HCl also targets Cdk12 kinase activity although at a higher concentration (IC50 = 250 nM).

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纯度 & 质量文件批次:

靶点选择性

生物活性

实验方案

技术信息

生物活性

靶点 Cdk7

IC50:3.2nM
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

Cell Data

Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
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

动物研究
剂量
Mice: 10 mg/kg i.p.^[3] i.v.^[4]

给药途径
i.p., i.v.
参考文献

动物研究
剂量	Mice: 10 mg/kg i.p.^[3] i.v.^[4]
给药途径	i.p., i.v.

[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.

实验方案

计算器摩尔计算器总药量计算器工作液计算器
储存液制备
- 1 mg
- 5 mg
- 10 mg
- 1 mM
- 1.5650 mL
- 7.8250 mL
- 15.6499 mL
- 5 mM
- 0.3130 mL
- 1.5650 mL
- 3.1300 mL
- 10 mM
- 0.1565 mL
- 0.7825 mL
- 1.5650 mL

技术信息

CAS号

2095433-94-4

储存条件

粉末: Inert atmosphere,2-8°C

液体: -20°C:3-6 月 -80°C:12月

分子式

C31H30Cl3N7O2

运输

蓝冰

分子量

638.97

别名

THZ1 Dihydrochloride

溶解度

DMSO	100.0 mg/mL (156.5 mM)
Water	Insoluble
Ethanol	Insoluble

动物实验配方

5% DMSO+45% PEG 300+water

4 mg/mL

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N-(3-((5-Chloro-4-(1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)-4-(4-(dimethylamino)but-2-enamido)benzamide dihydrochloride Catalog No. CSN19264

靶点选择性

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