1 research outputs found
Synthesis and Evaluation of Phosphorus Containing, Specific CDK9/CycT1 Inhibitors
Although
there is a significant effort in the design of a selective
CDK9/CycT1 inhibitor, no compound has been proven to be a specific
inhibitor of this kinase so far. The aim of this research was to develop
novel and selective phosphorus containing CDK9/CycT1 inhibitors. Molecules
bearing phosphonamidate, phosphonate, and phosphinate moieties were
synthesized. Prepared compounds were evaluated in an enzymatic CDK9/CycT1
assay. The most potent molecules were tested in cell-based toxicity
and HIV proliferation assays. Selectivity of shortlisted compounds
against CDKs and other kinases was tested. The best compound was shown
to be a highly specific, ATP-competitive inhibitor of CDK9/CycT1 with
antiviral activity