Bryan Roth, M.D., Ph.D. is a professor of pharmacology and director of the National Institute of Mental Health Psychoactive Drug Screening Program at UNC, and also a member of the UNC Lineberger Comprehensive Cancer Center and affiliate of the UNC Neuroscience Center.
They have developed a computational method that compares how similar the structures of all known drugs are to the naturally occurring binding partners, known as ligands, of disease targets within the cell. In a study published this week in Nature, the scientists showed that the method predicts potential new uses as well as unexpected side effects of approved drugs.
Many of the most successful drugs on the market today are being prescribed for ailments that are quite different from the ones they were originally designed to treat. Viagra, for instance, was once intended for coronary heart disease but now is used to combat erectile dysfunction. The discovery of surprising uses of developed drugs can sometimes be the result of serendipity, as unforeseen side effects emerge from clinical trials. In the past, researchers have tried to predict drug interactions by looking for chemical similarities among the possible targets of pharmaceutical compounds.
This team of researchers compared the structures of 3,365 FDA-approved and investigational drugs against the structures of hundreds of targets, defining each target by its ligands. They then honed in on thirty of the strongest predictions, validating the actual physical interactions between the drugs and targets in wet laboratory experiments.