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Thiuram disulfides as pseudo-irreversible inhibitors of lymphoid tyrosine phosphatase.

ABSTRACT: We screened a small library of thiuram disulfides for inhibition of lymphoid tyrosine phosphatase (LYP) activity. The parent thiuram disulfide, disulfiram, inhibited LYP activity in vitro and in Jurkat T?cells, whereas diethyldithiocarbamate failed to inhibit LYP at the concentrations tested. Compound 13, an N-(2-thioxothiazolidin-4-one) analogue, was found to be the most potent LYP inhibitor in this series, with an IC50 value of 3??M. Compound 13 inhibits LYP pseudo-irreversibly, as evidenced by the time-dependence of inhibition, with a K(i) value of 1.1??M and a k(inact) value of 0.004?s?¹. The inhibition of LYP by compound 13 could not be reversed significantly by incubation with glutathione or by prolonged dialysis, but could be partially reversed by incubation with dithiothreitol. Compound 13 also inhibited LYP activity in Jurkat T?cells.

SUBMITTER: Kulkarni RA

PROVIDER: S-EPMC3863632 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Thiuram disulfides as pseudo-irreversible inhibitors of lymphoid tyrosine phosphatase.

Kulkarni Rhushikesh A RA Stanford Stephanie M SM Vellore Nadeem A NA Krishnamurthy Divya D Bliss Matthew R MR Baron Riccardo R Bottini Nunzio N Barrios Amy M AM

ChemMedChem 20130719 9

We screened a small library of thiuram disulfides for inhibition of lymphoid tyrosine phosphatase (LYP) activity. The parent thiuram disulfide, disulfiram, inhibited LYP activity in vitro and in Jurkat T cells, whereas diethyldithiocarbamate failed to inhibit LYP at the concentrations tested. Compound 13, an N-(2-thioxothiazolidin-4-one) analogue, was found to be the most potent LYP inhibitor in this series, with an IC50 value of 3 μM. Compound 13 inhibits LYP pseudo-irreversibly, as evidenced b ...[more]

PMID: 23873737

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