Selective cyclin-dependent kinase inhibitors discriminating between cell cycle and transcriptional kinases: future reality or utopia?
Progression of the cell cycle is controlled by activating and inhibiting cellular factors. The delicate balance between these positive- and negative-acting regulators warrants proper cell cycle progression in normal cells and facilitates cellular response to a variety of stress stimuli. The increased activity of the positive regulators of the cell cycle in cancer cells is frequently accompanied by the loss or inactivation of the inhibitors of cyclin-dependent kinases (CDKs). The supplementation of the cellular CDK inhibitors by the pharmacological counterparts is a very promising therapeutic option. The generated pharmacological inhibitors of CDKs belong to different classes of compounds and display various CDK inhibitory features. In this article the action and specificity of CDK inhibitor roscovitine, belonging to the group of purine analogues, is reviewed and the rationale for dissecting the inhibitory action on cell cycle and transcriptional CDKs is discussed.
Wesierska-Gadek
Józefa
J
Cell Cycle Regulation Group, Department of Medicine I, Division Institute of Cancer Research, Medical University of Vienna, Vienna, Austria. Jozefa.Gadek-Wesierski@meduniwien.ac.at
Krystof
Vladimír
V
D000818:Animals; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology; D000077546:Roscovitine; D014158:Transcription, Genetic / Q000187:drug effects*
D047428:Protein Kinase Inhibitors; D011687:Purines; D000077546:Roscovitine; D016203:CDC2 Protein Kinase; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases