CDK inhibitors: from the bench to clinical trials.
Cell cycle deregulation is one of the first steps that transform normal cells into tumor cells. CDKs are a family of proteins devoted to controlling cell cycle entry, progression and exit. Studies from animal models show a tissue-specific essentiality of the single CDKs. In cancer cells, mis-regulation of CDK function is a common event. For this reason the pioneer compound Flavopiridol was developed and many new drugs are currently under development. ATP and the last generation of non-ATP competitive inhibitors are now emerging as one of the most potentially powerful target therapies. Many clinical trials are ongoing, as either a single agent or in combination with the classical cytotoxic agents. In this review, we discuss new strategies and methods to design more potent, selective and specific CDK inhibitors, starting from evidence emerging from animal and cancer cell models.
Rizzolio
Flavio
F
Department of Biology, Sbarro Institute for Cancer Research and Molecular Medicines, Centre for Biotechnology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania 19122, USA.
Tuccinardi
Tiziano
T
Caligiuri
Isabella
I
Lucchetti
Chiara
C
Giordano
Antonio
A
D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002986:Clinical Trials as Topic; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D016503:Drug Delivery Systems; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D000255:Adenosine Triphosphate; D018844:Cyclin-Dependent Kinases