• We specialize in small molecule inhibitors, agonists, antagonists and screening libraries!
Search Site
Related Products
THZ1Covalent CDK7 inhibitor,potent and selective

THZ1

Catalog No. A8882
Size Price Stock Qty
10mM (in 1mL DMSO) $100.00 In stock
5mg $80.00 In stock
10mg $150.00 In stock
25mg $300.00 In stock

Tel: +1-832-696-8203

Email: sales@apexbt.com

Worldwide Distributors

Sample solution is provided at 25 µL, 10mM.

Product Citations

1. Kemp MG. "DNA damage-induced ATR kinase activation in non-replicating cells is regulated by the XPB subunit of transcription factor II-H (TFIIH). J Biol Chem." 2017 Jun 7. pii: jbc.M117.788406. PMID:28592488
2. Francavilla C, Lupia M, et al. "Phosphoproteomics of Primary Cells Reveals Druggable Kinase Signatures in Ovarian Cancer." Cell Rep. 2017 Mar 28;18(13):3242-3256. PMID:28355574

Related Compound Libraries

Quality Control

Chemical structure

THZ1

Related Biological Data

THZ1

Related Biological Data

THZ1

Related Biological Data

THZ1

Biological Activity

Description THZ1 is an irreversible, potent and selective inhibitor of CDK7(cyclin-dependent kinase 7) with an IC50 value of 3.2 nM.
Targets CDK7          
IC50 3.2 nM          

Protocol

Cell experiment: [1]

Cell lines

Jurkat and Loucy T-ALL cell lines

Preparation method

The solubility of this compound in DMSO is <10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.

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 experiment: [1]

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.

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.

THZ1 Dilution Calculator

Concentration (start)
x
Volume (start)
=
Concentration (final)
x
Volume (final)
 
 
 
C1
V1
C2
V2

calculate

THZ1 Molarity Calculator

Mass
=
Concentration
x
Volume
x
MW*
 
 
 
g/mol

calculate

Chemical Properties

Cas No. 1604810-83-4 SDF Download SDF
Chemical Name (E)-N-(3-((5-chloro-4-(1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)-4-(4-(dimethylamino)but-2-enamido)benzamide
Canonical SMILES ClC1=CN=C(N=C1C2=CNC3=CC=CC=C23)NC4=CC=CC(NC(C5=CC=C(NC(/C=C/CN(C)C)=O)C=C5)=O)=C4
Formula C31H28ClN7O2 M.Wt 566.05
Solubility >28.3mg/mL in DMSO Storage Store at -20°C
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
Shipping Condition Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request

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.