NCIt definition : An orally bioavailable, selective inhibitor of the serine/threonine cyclin-dependent
kinase 9 (CDK9), the catalytic subunit of the RNA polymerase II (RNA Pol II) elongation
factor positive transcription elongation factor b (PTEF-b; PTEFb), with potential
antineoplastic activity. Upon oral administration, CDK9 inhibitor KB-0742 targets,
binds to and blocks the phosphorylation and kinase activity of CDK9, thereby preventing
PTEFb-mediated activation of RNA Pol II, leading to the inhibition of gene transcription
of various anti-apoptotic proteins and oncogenic transcription factors including MYC
and androgen receptor (AR). This induces cell cycle arrest and apoptosis and prevents
tumor cell proliferation. CDK9 regulates elongation of transcription through phosphorylation
of RNA Pol II at serine 2 (p-Ser2-RNAPII), and is an important cofactor for various
oncogenic transcription factors. It is upregulated in various tumor cell types and
plays a key role in the regulation of Pol II-mediated transcription of anti-apoptotic
proteins. Tumor cells are dependent on anti-apoptotic proteins for their survival.;