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Arylstibonic acids are potent and isoform-selective inhibitors of Cdc25a and Cdc25b phosphatases
Authors:Mak Lok Hang  Knott Jessica  Scott Katherine A  Scott Claire  Whyte Gillian F  Ye Yu  Mann David J  Ces Oscar  Stivers James  Woscholski Rudiger
Institution:Department of Chemistry, Imperial College London, Exhibition Road, London SW7 2AZ, UK.
Abstract:Arylstibonates structurally resemble phosphotyrosine side chains in proteins and here we addressed the ability of such compounds to act as inhibitors of a panel of mammalian tyrosine and dual-specificity phosphatases. Two arylstibonates both possessing a carboxylate side chain were identified as potent inhibitors of the protein tyrosine phosphatase PTP-ß. In addition, they inhibited the dual-specificity, cell cycle regulatory phosphatases Cdc25a and Cdc25b with sub-micromolar potency. However, the Cdc25c phosphatase was not affected demonstrating that arylstibonates may be viable leads from which to develop isoform specific Cdc25 inhibitors.
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