Side Effects Help Teach Old Drugs New Tricks

The seemingly endless list of possible side effects that accompanies each dispensed prescription medication may now hold the clue to identifying new uses for existing drugs. Unlike traditional drug discovery methods, which use molecular structure and binding assays, a team led by Peer Bork at Germany's Max Delbrück Center for Molecular Medicine, instead examined a drug's side effects (Science 2008, 321, 263). To identify chemically dissimilar drugs that bind the same protein, the team compiled listings of the side effects of more than 700 different drugs. Bork's team created a mathematical model to predict the likelihood that two different drugs would interact with the same protein. Of the 2,903 pairs of drugs predicted to target the same protein on the basis of their shared side effects, 754 pairs were from drugs used to treat entirely different clinical conditions. The group tested their predictions on 20 of these pairings through in vitro binding assays and found that in 13 of these, the drugs indeed bound to the same target. The researchers say this type of analysis shows that side effects can identify additional targets for an existing drug in unrelated disease categories.