Arylstibonic acids are potent and isoform-selective inhibitors of Cdc25a and Cdc25b phosphatases.
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.
Department of Chemistry, Imperial College London, Exhibition Road, London SW7 2AZ, UK.
Lok Hang
LH
Mak
Jessica
J
Knott
Katherine A
KA
Scott
Claire
C
Scott
Gillian F
GF
Whyte
Yu
Y
Ye
David J
DJ
Mann
Oscar
O
Ces
James
J
Stivers
Rudiger
R
Woscholski
D000965:Antimony / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000737:chemistry*; D007700:Kinetics; D009942:Organometallic Compounds / Q000737:chemistry*; D011422:Propionates / Q000737:chemistry*; D013329:Structure-Activity Relationship; D020687:cdc25 Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D004791:Enzyme Inhibitors; D009942:Organometallic Compounds; D011422:Propionates; D000965:Antimony; D020687:cdc25 Phosphatases