Because their neurological targets do not exist in yeast, the sensitivity we observe is likely a result of these compounds affecting additional cellular targets in yeast  these “secondary” targets, if conserved, may correspond to additional targets of these compounds in human cells.The cited paper is by Ericson et al. (PLoS Genetics) that seems to be rather underappreciated with just 6 citations in Web of Science (as of this writing). Both studies point to numerous non-GPCR off-targets of many drugs. I think the next step should be to indeed test the predicted drug targets, and I'm actually not quite sure why Hillenmeyer et al. didn't do this. Determining the affinities will be the only way to find out if the target found in yeast are relevant to human.
Friday, March 26, 2010
How to find non-GPCR targets for neuroactive drugs
In a follow-up to their Science paper, Hillenmeyer et al. recently published an extended analysis in Genome Biology. While the first paper was more focussed on the genes, this paper examines the chemicals in more detail. In particular, I am intrigued by this finding:
Posted by Michael Kuhn at 2:44 PM