title: Novel potent pharmacological cyclin-dependent kinase inhibitors.
abstract: Progression of the cell cycle is controlled by various activating and inhibiting cellular factors. The subtle balance between these counteracting regulators in normal cells ensures proper cell cycle progression and facilitates cellular responses to a variety of stress stimuli. Key activators include cyclin-dependent kinases (CDKs) and, consequently, loss or inactivation of CDK inhibitors contributes to the escape of cancer cells from cell cycle control and hyperactivation of CDKs occurs in various neurodegenerative disorders. However, these adverse effects may be compensated by pharmacological counterparts. Inhibitors of CDKs representing various classes of compounds with diverse CDK inhibitory patterns have been developed, but inhibitors that have high selectivity and offer highly targeted activity against both cell cycle and transcriptional CDKs are of particular interest. This review focuses on pharmacological CDK inhibitors that have entered clinical trials and some compounds that have been evaluated preclinically. Recent discoveries in cell cycle regulation have provided rationales for clinical applications of CDK inhibitors in both monotherapeutic and combined therapeutic regimens.
authors.affiliation: Cell Cycle Regulation Group, Department of Medicine, Institute of Cancer Research, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria. jozefa.gadek-wesierski@meduniwien.ac.at
authors.forename: Józefa
authors.initials: J
authors.lastname: Węsierska-Gądek
authors.forename: Ivo
authors.initials: I
authors.lastname: Chamrád
authors.forename: Vladimír
authors.initials: V
authors.lastname: Kryštof
mesh_terms: D002453:Cell Cycle / Q000187:drug effects; D002986:Clinical Trials as Topic; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016213:Cyclins / Q000737:chemistry / Q000378:metabolism; D006331:Heart Diseases / Q000188:drug therapy; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D019636:Neurodegenerative Diseases / Q000188:drug therapy; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000627:therapeutic use; D012319:RNA Polymerase II / Q000378:metabolism
chemical_list: D016213:Cyclins; D047428:Protein Kinase Inhibitors; D018844:Cyclin-Dependent Kinases; D012319:RNA Polymerase II