Is this a golden age of small-molecule drug discovery?

Abstract

At one stage, small-molecule drugs seemed at risk of going out of fashion, as industry began to favor biotherapeutics. But over the past 10 years, small molecules have made it clear that they aren’t going away. New classes of molecules, such as proteolysis-targeting chimeras (PROTACs) and molecular glues, have people excited. So do technologies, such as machine learning and generative artificial intelligence, that are helping drive drug discovery. Today, drug hunters have more ambition to go after difficult targets and to use novel chemistry. And that makes it an exciting time for chemists. Last year, sales of the 10 top-selling drugs were split 40:60 between small molecules and larger, more complicated biologics, according to Drug Discovery and Development . But those numbers are skewed by the huge cost of some biologic blockbusters. On a global scale, around 90% of all drugs sold are small molecules, according to a Medicine in