Abstract
Based on a previously identified lead structure, SC-alphaalphadelta9, we have developed a versatile new chemical scaffold that can be readily modified to generate libraries of both Tyr and dual specificity phosphatase inhibitors with reduced molecular weight and lipophilicity. The most potent analogue identified to date, aminothiazole 8z, inhibits the dual specificity phosphatase Cdc25B with a Ki of 4.6+/-0.4 microM and a Hill coefficient of 2.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Cell Cycle Proteins / antagonists & inhibitors
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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 / pharmacology
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Humans
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Inhibitory Concentration 50
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Phosphoprotein Phosphatases / antagonists & inhibitors*
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Protein Tyrosine Phosphatase, Non-Receptor Type 1
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Protein Tyrosine Phosphatases / antagonists & inhibitors
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Structure-Activity Relationship
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Sulfonic Acids / chemical synthesis
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Sulfonic Acids / pharmacology
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Thiazoles / chemical synthesis
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Thiazoles / pharmacology*
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cdc25 Phosphatases / antagonists & inhibitors
Substances
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Cell Cycle Proteins
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Enzyme Inhibitors
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Sulfonic Acids
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Thiazoles
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sulfamic acid
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Phosphoprotein Phosphatases
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CDC25B protein, human
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DUSP3 protein, human
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Dual Specificity Phosphatase 3
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PTPN1 protein, human
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Protein Tyrosine Phosphatase, Non-Receptor Type 1
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Protein Tyrosine Phosphatases
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cdc25 Phosphatases