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

Bioorg Med Chem. 2012 Jul 15;20(14):4371-6. doi: 10.1016/j.bmc.2012.05.040. Epub 2012 May 24.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimony / chemistry*
  • Enzyme Inhibitors / chemistry*
  • Kinetics
  • Organometallic Compounds / chemistry*
  • Propionates / chemistry*
  • Structure-Activity Relationship
  • cdc25 Phosphatases / antagonists & inhibitors*
  • cdc25 Phosphatases / metabolism

Substances

  • Enzyme Inhibitors
  • Organometallic Compounds
  • Propionates
  • Antimony
  • cdc25 Phosphatases