A yeast chemical genetics approach identifies the compound 3,4,5-trimethoxybenzyl isothiocyanate as a calcineurin inhibitor

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Abstract

The phosphatase enzyme calcineurin controls gene expression in a variety of biological contexts however few potent inhibitors are currently available. A screen of 360 plant extracts for inhibition of calcineurin-dependent gene expression in the model organism Saccharomyces cerevisiae identified the compound 3,4,5-trimethoxybenzyl isothiocyanate as an inhibitor. The compound was subsequently shown to inhibit human calcineurin via a mixed inhibition mechanism. To gain further mechanistic insight a yeast haploinsufficiency screen of 1152 deletion strains was carried out using a novel liquid medium screening method. The resulting haploinsufficiency profile is similar to that reported for the known calcineurin inhibitor FK506.

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Prescott, T. A. K., Panaretou, B., Veitch, N. C., & Simmonds, M. S. J. (2014). A yeast chemical genetics approach identifies the compound 3,4,5-trimethoxybenzyl isothiocyanate as a calcineurin inhibitor. FEBS Letters, 588(3), 455–458. https://doi.org/10.1016/j.febslet.2013.12.006

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