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• W2085648789 endingPage "2143" @default.
• W2085648789 startingPage "2133" @default.
• W2085648789 abstract "Abstract As the rational application of targeted therapies in cancer supplants traditional cytotoxic chemotherapy, there is an ever-greater need for a thorough understanding of the complex machinery of the cell and an application of this knowledge to the development of novel therapeutics and combinations of agents. Here, we review the current state of knowledge of the class of targeted agents known as cyclin-dependent kinase (CDK) inhibitors, with a focus on chronic lymphocytic leukemia (CLL). Flavopiridol (alvocidib) is the best studied of the CDK inhibitors, producing a dramatic cytotoxic effect in vitro and in vivo, with the principal limiting factor of acute tumor lysis. Unfortunately, flavopiridol has a narrow therapeutic window and is relatively non-selective with several off-target (i.e. non-CDK) effects, which prompted development of the second-generation CDK inhibitor dinaciclib. Dinaciclib appears to be both more potent and selective than flavopiridol, with at least an order of magnitude greater therapeutic index, and is currently in phase III clinical trials. In additional to flavopiridol and dinaciclib, we also review the current status of other members of this class, and provide commentary as to the future direction of combination therapy including CDK inhibitors." @default.
• W2085648789 created "2016-06-24" @default.
• W2085648789 creator A5000921376 @default.
• W2085648789 creator A5080781659 @default.
• W2085648789 date "2013-07-29" @default.
• W2085648789 modified "2023-09-27" @default.
• W2085648789 title "Emerging drug profile: cyclin-dependent kinase inhibitors" @default.
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