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

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

doi:10.1016/j.bmc.2012.05.040

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

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

School of Medicine

Research output: Contribution to journal › Article

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.

Original language	English (US)
Pages (from-to)	4371-4376
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry
Volume	20
Issue number	14
DOIs	https://doi.org/10.1016/j.bmc.2012.05.040
State	Published - Jul 15 2012

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Keywords

Arylstibonic acids
Cdc25 inhibitor
Protein tyrosine phosphatase

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

Cite this

Mak, L. H., Knott, J., Scott, K. A., Scott, C., Whyte, G. F., Ye, Y., Mann, D. J., Ces, O., Stivers, J., & Woscholski, R. (2012). Arylstibonic acids are potent and isoform-selective inhibitors of Cdc25a and Cdc25b phosphatases. Bioorganic and Medicinal Chemistry, 20(14), 4371-4376. https://doi.org/10.1016/j.bmc.2012.05.040

Arylstibonic acids are potent and isoform-selective inhibitors of Cdc25a and Cdc25b phosphatases. / Mak, Lok Hang; Knott, Jessica; Scott, Katherine A.; Scott, Claire; Whyte, Gillian F.; Ye, Yu; Mann, David J.; Ces, Oscar; Stivers, James; Woscholski, Rudiger.

In: Bioorganic and Medicinal Chemistry, Vol. 20, No. 14, 15.07.2012, p. 4371-4376.

Research output: Contribution to journal › Article

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10.1016/j.bmc.2012.05.040