Small molecules as inhibitors of cyclin-dependent kinases.
Cell division (mitosis) is one of the basic requirements for multicellular oranisms. The capability of a cell to replicate enables a complex assembly to be created. Faulty regulation of the control mechanism in the cell cycle leads to an excessive cell proliferation and is the cause of cancer. The key position of the cyclin-dependent kinases (CDKs) and their direct partners, as well as the fact that the majority of malign illnesses show defects in at least one of these key players of the cell cycle, is of great interest for the development of low-molecular-weight CDK inhibitors. In this Review an overview of the different structural classes of ATP-competitive inhibitors of CDKs are given, whose devlopment was aimed at battling cancer. The Review shows how far the development of selective CDK inhibitors has progressed and to what extent the expectations for such drugs have so far been fulfilled.
Huwe
Axel
A
Institut für Organische Chemie, Universität Leipzig, Johannisallee 29, 04103 Leipzig, Germany.
Mazitschek
Ralph
R
Giannis
Athanassios
A
D000818:Animals; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure; D008970:Molecular Weight
D047908:Intracellular Signaling Peptides and Proteins; C015482:protein kinase modulator; D018844:Cyclin-Dependent Kinases