This paper used computational methods based on chemical structural similarity to predict the off-target activity of 656 marketed drugs against 73 protein targets. About 600 of the ∼900 predictions were then tested experimentally, and around 50% were found to be genuine. For example, the methods predicted that the non-steroidal synthetic oestrogen chlorotrianisene (which is linked to abdominal pain) had potent affinity for cyclooxygenase 1 (an enzyme found in gastric mucosa); this prediction was confirmed using an ex vivo assay. So this model can detect previously unappreciated side effects, albeit with a high false-positive rate.
ORIGINAL RESEARCH PAPER
Lounkine, E. et al. Large-scale prediction and testing of drug activity on side-effect targets. Nature 486, 361–367 (2012)Article
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Harrison, C. Computational model predicts side effects. Nat Rev Drug Discov 11, 602 (2012). https://doi.org/10.1038/nrd3813
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DOI: https://doi.org/10.1038/nrd3813