PTPMT1, protein tyrosine phosphatase localized to the mitochondrion 1, is a recently discovered dual-specificity phosphatase implicated in the regulation of insulin secretion, suggesting PTPMT1 as a potential therapeutic target for type II diabetes. Identification of a selective small molecule inhibitor of PTPMT1 would provide a tool to further characterize the role of PTPMT1. To this end, Shenton et al. screened a commercial chemical library and identified the dibiguanide compound, alexidine dihydrochloride, as a selective inhibitor of PTPMT1. Using alexidine to study the function of PTPMT1, the authors uncovered an unusual kinetic mechanism of cooperative inhibition of PTPMT1 dimers. Treatment of cells with alexidine caused a dose-dependent increase in insulin secretion and inhibition of mitochondrial protein phosphorylation similar to that observed with genetic knockdown. Taken together, these observations not only support PTPMT1 as a pharmacological target for the treatment of type II diabetes but also provide a tool compound to study PTPMT1 function.
See article at J Pharmacol Exp Ther 2010, 333:584–592. (8935)
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