AZ'5576, a selective CDK9 inhibitor, demonstrates in vitro and in vivo activity in diverse preclinical models of nonHodgkin lymphoma

Abstract

Abstract Cyclin-dependent kinase 9 (Cdk9) is a serine/threonine kinase that regulates elongation of transcription through phosphorylation of RNA polymerase II at serine 2 (pSer2-RNAPII). Transient inhibition of Cdk9 results in modulation of genes with short-lived transcripts and labile proteins, thereby representing a potential therapeutic opportunity in tumors dependent upon oncogenes fitting these criteria. Mcl1, an anti-apoptotic protein that has been linked to increased survival and chemotherapy resistance in various cancers, and Myc, a proto-oncogenic transcription factor that coordinates diverse transcription programs and is over-expressed, amplified, or translocated in ..