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Arylstibonic acids are potent and isoform-selective inhibitors of Cdc25a and Cdc25b phosphatases. 2012
Lok Hang Mak, and
Jessica Knott, and
Katherine A Scott, and
Claire Scott, and
Gillian F Whyte, and
Yu Ye, and
David J Mann, and
Oscar Ces, and
James Stivers, and
Rudiger Woscholski
Department of Chemistry, Imperial College London, Exhibition Road, London SW7 2AZ, UK.
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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