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THZ1 Hydrochloride

现货
Catalog No.
B4736
CDK7抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,050.00
现货
5mg
¥ 800.00
现货
10mg
¥ 1,500.00
现货
25mg
¥ 3,000.00
现货

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Background

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.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt602.51
Cas No.1604810-83-4 (free base)
FormulaC31H29Cl2N7O2
Solubility≥30.1255mg/mL in DMSO
Chemical Name(E)-N-(3-((5-chloro-4-(1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)-4-(4-(dimethylamino)but-2-enamido)benzamide hydrochloride
SDFDownload SDF
Canonical SMILESClC(C=N1)=C(C2=CNC3=C2C=CC=C3)N=C1NC4=CC(NC(C5=CC=C(NC(/C=C/CN(C)C)=O)C=C5)=O)=CC=C4.Cl
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验: [1]

细胞系

Jurkat和Loucy T-ALL细胞系

制备方法

该化合物在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应条件

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

实验结果

作为CDK7抑制剂,THZ1有效抑制Jurkat和Lucy T-ALL细胞系的增殖,IC50值分别为50 nM和0.55 nM。

动物实验 [1]:

动物模型

KOPTK1异种移植小鼠

给药剂量

10 mg/kg,每天两次,持续29天

实验结果

在异种移植人T-ALL细胞系KOPTK1的生物发光小鼠模型中,10 mg/kg每日两次给药,THZ1表现出抗肿瘤功效。这些剂量的THZ1具有良好的耐受性,没有观察到体重减轻或行为改变,表明其在动物中没有明显的毒性。

注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[1] Kwiatkowski N, Zhang T, Rahl P B, et al. Targeting transcription regulation in cancer with a covalent CDK7 inhibitor. Nature, 2014, 511(7511): 616-620

质量控制

化学结构

THZ1 Hydrochloride