Biological Activity
THZ1 is a selective and potent covalent CDK7 inhibitor with an IC50 of 3.2 nM.
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].
References & source
Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.
