NCIt definition : A selective, short-acting 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 intravenous administration, zemirciclib 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.
This induces cell cycle arrest and apoptosis, and leads to a reduction in tumor cell
proliferation. CDK9 regulates elongation of transcription through phosphorylation
of RNA polymerase II at serine 2 (p-Ser2-RNAPII). 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.;