THZ1-Hydrochloride

Chemscene社は、高品質な低分子化合物を提供しているメーカーです。
Chemscene社のTHZ1-Hydrochlorideをご紹介します。

※本製品は研究用です。研究用以外には使用できません。

Name:THZ1 Hydrochloride; CDK7 inhibitor
Cat. No. :CS-3168
CAS No. :   
Formula:C31H29Cl2N7O2
M. Wt. : 602.51
Solubility:DMSO: 22.5 mg/mL

THZ1 Hydrochloride is a selective and potent covalent CDK7 inhibitor with IC50 of 3.2 nM.IC50 & Target: IC50: 3.2 nM (CDK7)[1]In Vitro: 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[1]. Low-dose THZ1 (50 nM) treatment causes selective inhibition of a number of oncogenic transcripts in oesophageal squamous cell carcinoma (OSCC)[2]. All genotypically-distinct human (hSCLC) cell lines exhibit high sensitivity to THZ1, with an IC50 in the range of 5-20 nM[3].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.p.) completely suppresses oesophageal squamous cell carcinoma tumour growth in vivo without loss of body weight or other common toxic effects[2]. THZ1 (10 mg/kg, i.v.) inhibits tumor growth in a mouse model of human MYCN-amplified NB and shows no toxicity[4].

Jiang YY, et al. Targeting super-enhancer-associated oncogenes in oesophageal squamous cell carcinoma. Gut. 2016 May 10. pii: gutjnl-2016-311818. Christensen CL, et al. Targeting transcriptional addictions in small cell lung cancer with a covalent CDK7 inhibitor. Cancer Cell. 2014 Dec 8;26(6):909-22. Chipumuro, et al. CDK7 inhibition suppresses super-enhancer-linked oncogenic transcription in MYCN-driven cancer. Cell. 2014 Nov 20;159(5):1126-39.   Kwiatkowski N, et al. Targeting transcription regulation in cancer with a covalent CDK7 inhibitor. Nature. 2014 Jul 31;511(7511):616-20.