Flavopiridol, the first cyclin-dependent kinase inhibitor: recent advances in combination chemotherapy.
The cell cycle is the series of events necessary for the division and duplication of a cell. The dysregulation of the cell cycle can promote the development of cancer. A group of proteins, cyclin-dependent kinases (CDKs), that control the cell cycle, provide new targets for treating cancer. As a result, cyclin-dependent kinase inhibitors (CDKIs) represent a novel class of chemotherapeutic agents. Of these, flavopiridol, a semisynthetic flavonoidal alkaloid, emerged as the first CDKI to enter clinical trials. Preclinical data indicate that flavopiridol could block the proliferation of neoplastic cells and induce programmed cell death as a single agent. Furthermore, recent emerging data revealed that flavopiridol can potentiate, generally in a dose- and sequence-dependent manner, the anti-tumor effects of many established chemotherapeutic agents. This review is primarily focused on the role of flavopiridol in combination with various therapeutic agents that are in or near clinical development.
The Department of Natural Products Chemistry, School of Pharmaceutical Science, Shandong University, 44 Wenhua Xi Road, Ji'nan 250012, Shandong Province, China.
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Ren
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D017321:Clinical Trials, Phase I as Topic; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D015195:Drug Design; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D005419:Flavonoids; D010880:Piperidines; C077990:alvocidib; D018844:Cyclin-Dependent Kinases