Cell cycle regulatory kinase modulators: interim progress and issues.
Since a prior review of cell cycle inhibitors developed at the National Cancer Institute, continued progress in the application of these molecules has been pursued. Evidence of preliminary activity on the part of flavopiridol in certain chronic leukemias has pointed to that disease area as of potential interest, but likely by affecting transcriptional regulation through non-cell cycle-related CDKs. Brief duration infusion early phase trials with UCN-01, and combination studies with cytotoxics are commencing. Emerging structural data has refined the basis for screening strategies directed at cell cycle regulatory kinases, including cdks, chk kinases and most recently the mitotic phase aurora kinases. This interval progress report will review and update progress in these related but distinct drug discovery and development interest areas.
Sausville
Edward A
EA
University of Maryland Marlene and Stewart Greenebaum Cancer Center, 22 South Greene St. Baltimore, MD 21201, USA. esausville@umm.edu
D020134:Catalytic Domain; D002453:Cell Cycle / Q000187:drug effects*; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D018844:Cyclin-Dependent Kinases