Thiuram Disulfides as Pseudo-irreversible Inhibitors of Lymphoid Tyrosine Phosphatase

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Author list: Kulkarni RA, Stanford SM, Vellore NA, Krishnamurthy D, Bliss MR, Baron R, Bottini N, Barrios AM
Publisher: Wiley: 12 months
Publication year: 2013
Volume number: 8
Issue number: 9
Start page: 1561
End page: 1568
Number of pages: 8
ISSN: 1860-7179
Languages: English-Great Britain (EN-GB)


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 Tcells, 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 mu M. Compound 13 inhibits LYP pseudo-irreversibly, as evidenced by the time-dependence of inhibition, with a K-i value of 1.1 mu 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 Tcells.


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Last updated on 2019-23-08 at 11:15