Abstract
Selective inhibitors of protein tyrosine phosphatases (PTPs) and dual-specificity phosphatases (DSPs) are expected to be useful tools for clarifying the biological functions of the PTPs themselves and also to be candidates for novel therapeutics. We planned a library approach for the identification of PTP/DSP inhibitors in which 3-acyltetronic acid is used as a "core" phosphate mimic. A series of novel tetronic acid derivatives were synthesized and evaluated as inhibitors of the dual-specificity protein phosphatases VHR and cdc25B. Several compounds are found to be potent inhibitors of cdc25B, which is a key enzyme for cell-cycle progression. The promising results described herein strongly indicated that this tetronic acid library is potent as a library focused on the PTP/DSP-selective inhibitor.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Cycle Proteins / antagonists & inhibitors*
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Cell Cycle Proteins / chemistry
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Cell Cycle Proteins / metabolism
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Combinatorial Chemistry Techniques
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Dual Specificity Phosphatase 3
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Escherichia coli / metabolism
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Furans / chemical synthesis*
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Furans / chemistry
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Models, Molecular
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Protein Binding
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Protein Tyrosine Phosphatases / antagonists & inhibitors*
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Protein Tyrosine Phosphatases / chemistry
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Protein Tyrosine Phosphatases / metabolism
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Structure-Activity Relationship
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cdc25 Phosphatases / antagonists & inhibitors*
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cdc25 Phosphatases / chemistry
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cdc25 Phosphatases / metabolism
Substances
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Cell Cycle Proteins
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Enzyme Inhibitors
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Furans
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Dual Specificity Phosphatase 3
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Protein Tyrosine Phosphatases
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cdc25 Phosphatases
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tetronic acid