Targeting Transcriptional Addiction by a Novel Highly Selective CDK9 Kinase Inhibitor for AML.

we reported a novel CDK9 high selective inhibitor JSH-009, it displayed high potency against CDK9 (IC50=1nM) and achieved high selectivity over CDKs family kinases (range from 200-10000 fold). JSH-009 showed high potent anti-proliferation effect in a range of AML cells and primary patient cells through downregulation of a number of transcriptional, apoptotic genes and related signaling pathways. In addition, this compound exhibited great anti-leukemic efficacy in the MV4-11 mediated xenograft, engraftment and AML PDX preclinical models. Currently, JSH-009 is under extensive preclinical development and We believe the work presented here would be of great interest to readers of Leukemia. AML cell HL60's mRNA profiles of JSH-009 treatment and DMSO treatment were generated by deep sequencing, in two replicates, using Illumina HiSeq2000.