Drug Repurposing: Then, Now, and in the Future

Contrary to the definition of a drug, drug repurposing usually involves the redevelopment of an active pharmaceutical ingredient (API) for a substantially different medical use; only rarely is this done with an off-the-shelf drug approved for a different disease. There is a qualitative difference between API redevelopment and additional approvals for an existing drug; to qualify as repurposing, the additional therapeutic indication must not be closely related to the original one. Using the mechanism for which the drug is approved and marketed to treat a different disease context is called on-target repurposing, and while the new use may seem obvious in retrospect, it requires ingenuity to connect the dots of evidence leading to it. Off-target repurposing is even more innovative: it relies on a newly discovered mechanism, or one that was known but only considered in terms of the drug's side effects. While clever pharmacological thinking and occasional serendipity have long driven repurposing, algorithmic approaches are now making their mark, and more recently, artificial intelligence applications are taking drug repurposing to unprecedented levels.