151. A yeast chemical genetics approach identifies the compound 3,4,5-trimethoxybenzyl isothiocyanate as a calcineurin inhibitor.
- Author
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Prescott TA, Panaretou B, Veitch NC, and Simmonds MS
- Subjects
- Calcineurin Inhibitors, Cell Line, Enzyme Inhibitors, Gallic Acid chemistry, Gallic Acid isolation & purification, Humans, Immunosuppressive Agents pharmacology, Plant Extracts chemistry, Saccharomyces cerevisiae drug effects, Saccharomyces cerevisiae genetics, Tacrolimus pharmacology, Calcineurin biosynthesis, Gallic Acid analogs & derivatives, Gene Expression Regulation, Fungal drug effects, Plant Extracts pharmacology
- 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., (Copyright © 2013 Federation of European Biochemical Societies. All rights reserved.)
- Published
- 2014
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