Cell Cycle Regulatory Kinase Modulators: Interim Progress and Issues

Edward   A.   Sausville

Abstract

Since a prior review of cell cycle inhibitors developed at the National Cancer Institute, (Sausville E.A.; Curr Med Chem -Anti Cancer Agents 2003, 3, 47) 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.

Keywords: anti-proliferative agent, cyclin dependent kinase 1, combinatorial approaches, checkpoint regulation, ucn-01, flavopiridol

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