tacrolimus and 3-4-5-trimethoxybenzoic-acid

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.

Topics: Calcineurin; Calcineurin Inhibitors; Cell Line; Enzyme Inhibitors; Gallic Acid; Gene Expression Regulation, Fungal; Humans; Immunosuppressive Agents; Plant Extracts; Saccharomyces cerevisiae; Tacrolimus