Arylstibonic acids are potent and isoform-selective inhibitors of Cdc25a and Cdc25b phosphatases

芳基锑酸是 Cdc25a 和 Cdc25b 磷酸酶的有效异构体选择性抑制剂

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作者:Lok Hang Mak, Jessica Knott, Katherine A Scott, Claire Scott, Gillian F Whyte, Yu Ye, David J Mann, Oscar Ces, James Stivers, Rudiger Woscholski

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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