Abstract
The dual specificity CDC25 phosphatases dephosphorylate two inhibitory phospho-amino acids of cyclin-dependent kinases, a major family of cell cycle regulators. CDC25 inhibitors constitute new anti-mitotic agents with potential anticancer activity. While screening through a collection of natural products derived from marine organisms for CDC25A inhibitors, we purified and identified coscinosulfate 1, a sesquiterpene sulfate from the New Caledonian sponge Coscinoderma matthewsi, along with 4. The purified compound 1 displayed significant inhibitory activity towards CDC25A (IC(50): 3 microM).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / isolation & purification*
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Antineoplastic Agents / pharmacology
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / isolation & purification
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Enzyme Inhibitors / pharmacology
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Humans
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Inhibitory Concentration 50
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Magnetic Resonance Spectroscopy
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Molecular Structure
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Porifera / chemistry*
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Recombinant Fusion Proteins / antagonists & inhibitors
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Sesquiterpenes / chemistry
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Sesquiterpenes / isolation & purification
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Sesquiterpenes / pharmacology
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Terpenes / chemistry
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Terpenes / isolation & purification*
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Terpenes / pharmacology
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cdc25 Phosphatases / antagonists & inhibitors*
Substances
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Antineoplastic Agents
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Enzyme Inhibitors
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Recombinant Fusion Proteins
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Sesquiterpenes
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Terpenes
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coscinosulfate
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cdc25 Phosphatases