Teaching old drugs new tricks( Researchers from the European Molecu...)

Researchers from the European Molecular Biology Laboratory (EMBL) discovered a new way to make use of drugs' unwanted side effects. They developed a computational method that compares how similar the side effects of different drugs are and predicts how likely the drugs act on the same target molecule. The study, published in Science this week, hints at new uses of marketed drugs.

Similar drugs often share target proteins, modes of action and unpleasant side effects. In reverse this means that drugs that evoke similar side effects likely act on the same molecular targets. A team of EMBL researchers now developed a computational tool that compares side effects to test if they can predict common targets of drugs.

"Such a correlation not only reveals the molecular basis of many side effects, but also bears a powerful therapeutic potential. It hints at new uses of marketed drugs in the treatment of diseases they were not specifically developed for," says Peer Bork, Joint Coordinator of EMBL's Structural and Computational Biology Unit.

The approach would prove particularly useful for chemically dissimilar drugs used in different therapeutic areas that nevertheless have an overlapping, so far unknown protein target profile. Similar strategies have proven successful in the past. For example, the drug marketed as Viagra was initially developed to treat angina, but its side effects of prolonged penile erection led to a change in its therapeutic area.

Applying the new method to 746 marketed drugs, the scientists found 261 dissimilar drugs that in addition to their known action also likely bind to other unexpected molecular targets. 20 of these drugs were then tested experimentally and 13 showed binding to the targets that were predicted by side effect similarity. Testing 9 of these drugs further in cellular assays they all showed activity and thus a desired effect on the cell through their interaction with the newly discovered
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