Recent advances and new directions in the discovery and development of cyclin-dependent kinase inhibitors.

摘要: The eukaryotic cell division cycle is coordinated by cyclin-dependent protein kinases (CDKs) and cyclin subunits specific for the different phases of cycle. These complexes phosphorylate target substrates, including retinoblastoma susceptibility gene product (pRb) related proteins. Cellular neoplastic transformations are accompanied loss regulation checkpoints, frequently through aberrant expression CDKs cyclins, as well or mutation their negative regulators. Consequently, one strategy in development mechanism-based anticancer therapeutics has been to halt malignant cellular proliferation inhibition enzymatic activity CDKs. inhibitors selective ATP binding sites particular a comparatively recent medicinal chemistry endeavor. Advances relevant CDK reviewed critically alternative approaches inhibition, applications therapeutic areas other than oncology, also discussed.