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

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

来源：Bioorganic & Medicinal Chemistry, 2012, 20(14): 4371-4376.

DOI：10.1016/j.bmc.2012.05.040

• Arylstibonic acids
• Protein tyrosine phosphatase
• Cdc25 inhibitor

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-beta. 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.

• 出版日期2012-7-15