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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
CAS NO:1604810-83-4
规格:≥98%
包装与价格:
包装价格(元)
1mg电议
2mg电议
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW)566.05
FormulaC31H28ClN7O2
CAS No.1604810-83-4 (free);
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 28.3mg/mL
Water: <1 mg/mL
Ethanol: N/A
SMILES O=C(NC1=CC=CC(NC2=NC=C(Cl)C(C3=CNC4=C3C=CC=C4)=N2)=C1)C5=CC=C(NC(/C=C/CN(C)C)=O)C=C5
Synonyms THZ-1; THZ 1; THZ1
实验参考方法
In Vitro

In vitro activity: THZ1 uses a unique mechanism, combining ATP-site and allosteric covalent binding, as a means of attaining potency and selectivity for CDK7. THZ1 irreversibly inhibits RNAPII CTD phosphorylation by covalently targeting a unique cysteine located outside the kinase domain of CDK7. THZ1, but not THZ1-R, completely inhibits the phosphorylation of the established intracellular CDK7 substrate RNAPII CTD at Ser 5 and Ser 7, with concurrent loss of Ser 2 phosphorylation at 250 nM in Jurkat cells. THZ1 exhibits strong antiproliferative effects across a broad range of cancer cell lines from various cancer types. In Jurkat cells, low-dose THZ1 has a profound effect on a small subset of genes, including the key regulator RUNX1, thus contributing to subsequent loss of the greater gene expression program and cell death. THZ1 causes defects in Pol II(polymerase II) phosphorylation, co-transcriptional capping, promoter proximal pausing, and productive elongation.


Kinase Assay: THZ1 is a novel selective and potent covalent CDK7 inhibitor with IC50(binding affinity) of 3.2 nM.


Cell Assay: Cells (Jurkat, Loucy, KOPTK1 and DND-41 cell lines) are treated with THZ1, THZ1-R or dimethylsulphoxide (DMSO) for 0-6 h to assess the effect of time on the THZ1-mediated inhibition of RNAPII CTD phosphorylation. For subsequent experiments cells are treated with compounds for 4 h as determined by the time-course experiment described earlier, unless otherwise noted. For inhibitor washout experiments, cells are treated with THZ1, THZ1-R or DMSO for 4 h. Medium containing inhibitors is subsequently removed to effectively 'washout' the compound and the cells are allowed to grow in the absence of inhibitor. For each experiment, lysates are probed for RNAPII CTD phosphorylation and other specified proteins.

In VivoTHZ1 reduces the proliferation of KOPTK1 T-ALL cells in a human xenograft mouse model. THZ1 is well tolerated at 10 mg/kg with no observable body weight loss or behavioural changes, suggesting that it causes no overt toxicity in the animals
Animal modelBioluminescent xenografted mouse model
Formulation & DosageFormulated in 10% DMSO in D5W; 10 mg/kg; i.v. injection
References

Nature. 2014 Jul 31;511(7511):616-20; Mol Cell. 2015 Aug 20;59(4):576-87.