Discovery and pharmacological characterization of a novel series of highly selective inhibitors of cyclin-dependent kinases 4 and 6 as anticancer agents.

ABSTRACT:

Background and purpose

Cyclin D-dependent kinases 4 and 6 (CDK4/6) are crucial regulators of the G1 to S phase transition of the cell cycle and are actively pursued as therapeutic targets in cancer. We sought to discover a novel series of orally bioavailable and highly selective small molecule inhibitors of CDK4/6.

Experimental approach

The discovery of pharmacological inhibitors and optimization for potency, selectivity and drug properties were achieved by iterative chemical synthesis, biochemical screening against a panel of kinases, cell-based assays measuring cellular viability, cell cycle distribution, induction of apoptosis and the level of retinoblastoma tumour suppressor protein (Rb) phosphorylation and E2 factor (E2F)-regulated gene expression and in vitro biopharma

SUBMITTER: Tadesse S 

PROVIDER: S-EPMC5980294 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature