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THZ1

THZ1

Catalog No.

A8882

Covalent CDK7 inhibitor,potent and selective

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Grouped product items
Size	Price	Stock
10mM (in 1mL DMSO)	$100.00	In stock
5mg	$80.00	In stock
10mg	$150.00	In stock
25mg	$300.00	In stock

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Background
Product Citation
Chemical Properties
Protocol
Biological Activity
Quality Control

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.

Product Citation

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Chemical Properties

Storage	Store at -20°C
M.Wt	566.05
Cas No.	1604810-83-4
Formula	C₃₁H₂₈ClN₇O₂
Solubility	≥28.3025 mg/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
SDF	Download SDF
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
Shipping Condition	Evaluation sample solution: ship with blue ice. All other available sizes: ship with RT, or blue ice upon request.
General tips	For obtaining a higher solubility, please warm the tube at 37°C and shake it in the ultrasonic bath for a while. Stock solution can be stored below -20°C for several months.

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 10 mg/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.

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