JSH-150 是一种高选择性的CDK9抑制剂， IC50为 1 nM。

JSH-150 is a highly selective CDK9 inhibitor(IC50 : 1 nM).

A highly selective inhibitor compound 40 (JSH-150), which exhibited an IC50 of 1 nM against CDK9 kinase in the biochemical assay and achieved around 300 10000-fold selectivity over other CDK kinase family members.?In addition, it also displayed high selectivity over other 468 kinases/mutants (KINOMEscan S score(1) = 0.01).Compound 40 displayed potent antiproliferative effects against melanoma, neuroblastoma, hepatoma, colon cancer, lung cancer as well as leukemia cell lines.?It could dose-dependently inhibit the phosphorylation of RNA Pol II, suppress the expression of MCL-1 and c-Myc, arrest the cell cycle and induce the apoptosis in the leukemia cells.

In the MV4-11 cell-inoculated xenograft mouse model, 10 mg/kg dosage of 40 could almost completely suppress the tumor progression.?The high selectivity and good in vivo PK/PD profile suggested that 40 would be a good pharmacological tool to study CDK9-mediated physiology and pathology as well as a potential drug candidate for leukemia and other cancers.

2247481-21-4

C24H33ClN6O2S

505.08

DMSO:16 mg/mL (31.68 mM),Need ultrasonic
Powder: -20°C for 3 years
In solvent: -80°C for 2 years