THZ1 2HCl

Catalog No.S7549

For research use only.

THZ1 is a covalent CDK7 inhibitor which has the unprecedented ability to target a remote cysteine residue located outside of the canonical kinase domain, providing an unanticipated means of achieving selectivity for CDK7.

THZ1 2HCl Chemical Structure

CAS No. 2095433-94-4

Selleck's THZ1 2HCl has been cited by 21 publications

Purity & Quality Control

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Biological Activity

Description THZ1 is a covalent CDK7 inhibitor which has the unprecedented ability to target a remote cysteine residue located outside of the canonical kinase domain, providing an unanticipated means of achieving selectivity for CDK7.
Targets
CDK7 [1]
(Cell-based assay)
3.2 nM
In vitro

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[1]. THZ1 causes defects in Pol II(polymerase II) phosphorylation, co-transcriptional capping, promoter proximal pausing, and productive elongation[2].

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Jurkat cells MVPDfZRwfG:6aXPpeJkh[XO|YYm= MX23NkBp MnvSR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gTpVzc2G2IHPlcIx{KGG|c3Xzd4VlKGG|IHPlcIwhfmmjYnnsbZR6KGGodHXyJFczKGi{czDifUBz\XOjeoXybY4h[XO|YYmsJGlEPTB;MD6wOUDPxE1? NXjKTldmRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[xNVU2PzFpPkK2NVE2PTdzPD;hQi=>
Assay
Methods Test Index PMID
Western blot pS2 / pS5 / pS7 / RNAPII / MYCN / MCL-1 / Cleaved PARP ; KLF5 / FGFBP / c-MYC ; RNP2-p-Ser2 / RNP2-p-Ser5 / RNP2-p-Ser7 / CDK7 29276047 31360115 31399555
Growth inhibition assay Cell viability 31399555
In vivo THZ1 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[1].

Protocol (from reference)

Cell Research:[1]
  • Cell lines: Jurkat, Loucy, KOPTK1 and DND-41 cell lines
  • Concentrations: 0-10 μM
  • Incubation Time: 4 h
  • Method: Cells 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.
Animal Research:[1]
  • Animal Models: Bioluminescent xenografted mouse model
  • Dosages: 10 mg/kg
  • Administration: i.v.

Solubility (25°C)

In vitro

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
5% DMSO+45% PEG 300+ddH2O
For best results, use promptly after mixing.

4mg/mL

Chemical Information

Molecular Weight 638.97
Formula

C31H30Cl3N7O2

CAS No. 2095433-94-4
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CN(C)CC=CC(=O)NC1=CC=C(C=C1)C(=O)NC2=CC=CC(=C2)NC3=NC=C(C(=N3)C4=CNC5=CC=CC=C54)Cl

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

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Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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