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• W39858769 abstract "Protein kinase C (PKC) is a family of serine/threonine-directed protein kinases that are pivotal regulators of cellular growth, transformation and death. PKC has therefore been considered to be a suitable target for novel antineoplastic drugs. Twenty years ago, staurosporine was isolated from bacteria and identified as a potent inhibitor of PKC activity. Its analogs UCN-01 and CGP 41251 effectively arrest the growth of several human-derived tumor cell lines in vitro. They also possess antineoplastic activity in vivo in human tumors grown as xenografts in nude mice. CGP 41251 reverses the multidrug-resistance phenotype of cancer cells. Both agents are currently under clinical evaluation as potential antitumor drugs. Staurosporine analogs inhibit “conventional” PKC isoenzymes more potently than “novel” and “atypical” ones. They are also potent modulators of the cyclin-dependent kinase system, which determines the progression of cells through the cell cycle. The nature of this interaction is complex. UCN-01 blocks cells in G1 phase by promoting accumulation of dephosphorylated retinoblastoma protein as a consequence of inhibition of the activity of certain cyclin-dependent kinases, downregulation of their partner cyclins and an increase in the expression of cyclin-dependent kinase inhibitor proteins. Preliminary results of early clinical trials suggest that UCN-01 and CGP41251 are without remarkable toxicity but display high binding to human plasma protein." @default.
• W39858769 created "2016-06-24" @default.
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• W39858769 date "1998-11-01" @default.
• W39858769 modified "2023-10-18" @default.
• W39858769 title "Analogs of Staurosporine" @default.
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• W39858769 doi "https://doi.org/10.1016/s0306-3623(98)00069-x" @default.
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