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Sep 11, 2008
 |  BC Innovations  |  Tools & Techniques

Nature of the Yeast

University of Toronto researchers have developed a yeast-based strategy to identify off-target effects of psychoactive drugs.1 The approach could provide an early screen to find compounds with improved side effects and has already been licensed by a handful of biopharma companies. The unanswered question is whether findings in yeast will correlate with effects in humans.

Targets of traditional antipsychotics include dopaminereceptors. Side effects associated with these first-generation drugs range from sexual and reproductive issues to seizures.2 The impact on quality of life and patient compliance with these drugs prompted development of the next generation of drugs, dubbed atypical antipsychotics, which often target both serotonin (5-HT) and dopamine receptors. Atypical antipsychotics have been linked to cardiovascular and neurological problems such asmyocarditis and agranulocytosis.3

Corey Nislow and colleagues at the University of Toronto have developed a screening method that uses a library of yeast strains with single gene deletions to help identify the genes or pathways potentially responsible for a compound's side effects. In their PLoS Genetics paper describing the method, the researchers propose that the approach might help identify compounds with improved side-effect profiles.

According to Nislow, because yeast does not express the primary targets of either typical or atypical antipsychotics, any effects of a compound on yeast growth can be attributed to activity on secondary targets.

The hypothesis is that the equivalent human genes and pathways may be responsible for...

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