Adverse drug reactions can limit the clinical use of otherwise effective drugs, and are the leading cause of failure for new drugs in clinical trials. Drugs frequently interact with more than one protein target, and hundreds of such proteins are linked to the side effects of clinically used therapeutics. This large-scale computational study predicted the activity of 656 drugs against 73 protein targets that have been associated with adverse drug reactions. Of the 1,042 predictions tested, approximately half were confirmed. One prediction was that abdominal pain, a known side effect of the synthetic oestrogen chlorotrianisene, was mediated through its inhibition of COX-1, and the clinical relevance of this inhibition was borne out in whole human blood platelet-aggregation assays. The researcher’s approach could be used to weed out drugs most likely to fail before they go to clinical trial.
- (News & Views p326, doi: 10.1038/nature11198)
- Large-scale prediction and testing of drug activity on side-effect targets (Article p361, doi: 10.1038/nature11159)
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