NCIt definition : A 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 administration, the CDK9 inhibitor GFH009 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.
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). 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.;