Home Cell Cycle CDK inhibitor THZ1 2HCl For research use only.

THZ1 2HCl

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

THZ1 2HCl Chemical Structure

CAS No. 2095433-94-4

Purity & Quality Control

THZ1 2HCl Related Products

Signaling Pathway

CDK Signaling Pathways

CDK Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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
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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
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 Research 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.
Experimental Result Images Methods Biomarkers Images 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
Growth inhibition assay Cell viability 31399555
In Vivo
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].
Animal Research Animal Models Bioluminescent xenografted mouse model
Dosages 10 mg/kg
Administration i.v.

Chemical Information & Solubility

Molecular Weight 638.97 Formula

C31H30Cl3N7O2
CAS No. 2095433-94-4 SDF Download THZ1 2HCl SDF
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
Storage (From the date of receipt)

In vitro
Batch:

Water : Insoluble

Ethanol : Insoluble


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In vivo
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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.

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