THZ1 Hydrochloride 是有效，选择性的共价 CDK7 抑制剂，IC₅₀ 为 3.2 nM。THZ1 Hydrochloride 还抑制相关的激酶 CDK12 和 CDK13，并下调 MYC 表达。

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.

Solid

CDK7 3.2 nM (IC50) CDK12

THZ1 inhibits Jurkat cell and Loucy cell with IC50 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.
All genotypically-distinct human (hSCLC) cell lines exhibit high sensitivity to THZ1, with an IC50 in the range of 5-20 nM.

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.
THZ1 (10 mg/kg, i.v.) inhibits tumor growth in a mouse model of human MYCN-amplified NB and shows no toxicity.
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. has not independently confirmed the accuracy of these methods. They are for reference only.

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moistur In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

[1]. Kwiatkowski N, et al. Targeting transcription regulation in cancer with a covalent CDK7 inhibitor. Nature. 2014 Jul 31;511(7511):616-20.
[2]. Jiang YY, et al. Targeting super-enhancer-associated oncogenes in oesophageal squamous cell carcinoma. Gut. 2016 May 10. pii: gutjnl-2016-311818.
[3]. Christensen CL, et

In Vitro: DMSO : 22.5 mg/mL (37.34 mM; Need ultrasonic and warming)H₂O : < 0.1 mg/mL (ultrasonic;warming;heat to 60°C) (insoluble)配制储备液