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THZ1
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
THZ1图片
包装与价格:
包装价格(元)
10mM (in 1mL DMSO)电议
5mg电议
10mg电议
25mg电议

产品介绍
THZ1 是一种选择性和有效的共价 CDK7 抑制剂,IC50 为 3.2 nM。 THZ1 还抑制密切相关的激酶 CDK12 和 CDK13 并下调 MYC 表达。

Cell lines

Jurkat and Loucy T-ALL cell lines

Preparation method

The solubility of this compound in DMSO is

Reaction Conditions

72 hours IC50: 50 nM (for Jurkat cells), 0.55 nM (for Loucy T-ALL cells)

Applications

As a CDK7 inhibitor, THZ1 potently inhibited proliferation of Jurkat and Loucy T-ALL cell lines with IC50 values of 50 nM and 0.55 nM, respectively.

Animal models

Mice bearing KOPTK1 xenografts

Dosage form

10 mg/kg, twice daily for 29 days

Applications

THZ1 exhibited efficacy in a bioluminescent xenografted mouse model using the human T-ALL cell-line KOPTK1 when dosed twice daily at 10mg/kg. THZ1waswell tolerated at these doseswith no observable body weight loss or behavioural changes, suggesting that it caused no overt toxicity in the animals.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

产品描述

THZ1 is a covalent inhibitor of CDK7 with IC50 value of 3.2nM [1].

THZ1 covalently modifies CDK7 by targeting C312 residue outside of the kinase domain, providing an unanticipated means of achieving covalent selectivity. THZ1 potently inhibits proliferation of Jurkat and Loucy T-ALL cell lines with IC50 values of 50nM and 0.55nM, respectively. In the kinase binding assay, THZ1 shows a good binding affinity with IC50 value of 3.2nM [1].

As an inhibitor of CDK7, THZ1 inhibits the phosphorylation of the C-terminal domain of RNAP polymerase II, effecting the regulation of transcription. THZ1 also inhibits the activation of the CDK proteins. It is reported to disrupt the CDK7 signalling pathways both in Jurkat cells and Loucy cells. THZ1 shows a broad-based activity with IC50 values less than 200nM in a variety of cancer cell lines. Among these cell lines, T-ALL is exceptional sensitivity to THZ1 due to the transcription effect of RUNX1 caused by THZ1 [1].

References:
[1] Nicholas Kwiatkowski, Tinghu Zhang, Peter B. Rahl et al. Targeting transcription regulation in cancer with a covalent CDK7 inhibitor. Nature, 2014.