[CAS NO. ] THZ1Hydrochloride

Name: THZ1Hydrochloride
Brand: Arctom Scientific
SKU: HY-80013A

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PRODUCTS SPECIFICATIONS

Distributor

Catalog

HY-80013A

Brand

MCE

CAS

-

DESCRIPTION

Overview

MDL	-
Molecular Weight	602.51
Molecular Formula	C31H29Cl2N7O2
SMILES	ClC1=CN=C(NC2=CC(NC(C3=CC=C(NC(/C=C/CN(C)C)=O)C=C3)=O)=CC=C2)N=C1C4=CNC5=CC=CC=C54.Cl

For research use only. We do not sell to patients.

62 Publications Citing Use of MCE

Summary

THZ1 Hydrochloride is a selective and potent covalent CDK7 inhibitor with an IC ₅₀ of 3.2 nM. THZ1 Hydrochloride also inhibits the closely related kinases CDK12 and CDK13 and downregulates MYC expression ^[1] ^[2] .

IC50 & Target

CDK7

3.2 nM (IC ₅₀ )

CDK12

CDK13

In Vitro

THZ1 inhibits Jurkat cell and Loucy cell with IC ₅₀ of 50 nM, and 0.55 nM, respectively. THZ1 demonstrates time-dependent inhibition of CDK7 in vitro and covalent binding of intracellular CDK7. THZ1 (9, 27, 83, 250, 750, and 2500 nM) inhibits CDK12 but at higher concentrations compared to CDK7. THZ1 (1 μM) irreversibly inhibits RNAPII CTD and CAK phosphorylation. THZ1 (2.5 µM) irreversibly inhibits RNAPII CTD phosphorylation by covalently targeting a unique cysteine located outside the kinase domain of CDK7 in Hela S3 cells. THZ1 (250 nM) causes decreased cellular proliferation and an increase in apoptotic index with concomitant reduction in anti-apoptotic proteins, most notably MCL-1 and XIAP in T-ALL cell lines ^[1] .
All genotypically-distinct human (hSCLC) cell lines exhibit high sensitivity to THZ1, with an IC ₅₀ in the range of 5-20 nM ^[3] .

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

THZ1 (10 mg/kg) demonstrates potent killing of primary chronic lymphocytic leukemia (CLL) cells and anti-proliferative activity against primary TALL cells and in vivo against a human T-ALL xenograft ^[1] .
THZ1 (10 mg/kg, i.v.) inhibits tumor growth in a mouse model of human MYCN-amplified NB and shows no toxicity ^[4] .
THZ1 (10 mg/kg, i.p.) completely suppresses oesophageal squamous cell carcinoma tumour growth in vivo without loss of body weight or other common toxic effects ^[5] .

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Appearance

Solid

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

4°C, sealed storage, away from moisture

* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

Solvent & Solubility

In Vitro:

DMSO : 22.5 mg/mL ( 37.34 mM ; Need ultrasonic and warming)

H ₂ O : < 0.1 mg/mL (ultrasonic;warming;heat to 60°C) (insoluble)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	1.6597 mL	8.2986 mL	16.5972 mL
5 mM	0.3319 mL	1.6597 mL	3.3194 mL
10 mM	0.1660 mL	0.8299 mL	1.6597 mL

* Please refer to the solubility information to select the appropriate solvent.

In Vivo:

1.

Add each solvent one by one: 10% DMSO >> 40% PEG300 >> 5% Tween-80 >> 45% saline

Solubility: ≥ 2.17 mg/mL (3.60 mM); Clear solution
2.

Add each solvent one by one: 10% DMSO >> 90% (20% SBE-β-CD in saline)

Solubility: 2.17 mg/mL (3.60 mM); Suspended solution; Need ultrasonic
3.

Add each solvent one by one: 10% DMSO >> 90% corn oil

Solubility: ≥ 2.17 mg/mL (3.60 mM); Clear solution

* All of the co-solvents are available by MCE.