Sulfonyl-bridged Calix[4]arene as an Inhibitor of Protein Tyrosine Phosphatases

Vladyslav Buldenko, Oleksandr Kobzar, Viacheslav Trush, Andriy Drapailo, Vitaly Kalchenko, Andriy Vovk


Previously, phosphonic acid derivatives of calix[4]arene and thiacalix[4]arene were found to be potential inhibitors of protein tyrosine phosphatase 1B. In the present paper, the inhibitory activity of unsubstituted sulfonyl-bridget calix[4]arene towards some of the therapeutically important protein tyrosine phosphatases has been established. The obtained results showed that the sulfonylcalix[4]arene is able to inhibit protein tyrosine phosphatase MEG2 with IC50 value in the micromolar range. At the same time, the inhibitor demonstrated lower activity in case of other protein tyrosine phosphatases such as PTP1B, MEG1, TC-PTP, SHP2, and PTPβ. The performed molecular docking indicated that the inhibitor binds to the active site region of MEG2 and PTP1B with WPD-loop in the open conformation.


sulfonylcalix[4]arene; protein tyrosine phosphatase MEG2; PTP1B; inhibition; molecular docking

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