Small molecules and their importance as therapeutic options in daily practice

Just when newer technologies threaten to render them obsolete, small-molecule drugs are on their way to becoming first-in-class drugs in allergy and immunology. This is why understanding how they fit into the treatment paradigm is key for modern clinical decision-making. In various disease states, small molecules have therapeutic applications seen in daily practice, with more on the horizon. With many targeted therapeutic uses, they can easily diffuse across cell membranes, affect other molecules once inside, and achieve the desired biological outcome. Although oral formulation is a possibility and often an advantage, they can also be delivered as topicals, injectables, and aerosols. What is more, we have seen, studied, and used many of these compounds, perhaps more frequently than any other category of medication in our field. Beyond their strong legacy in the therapeutic world, small molecules have now expanded their repertoire by hitting nodes that biologics cannot (eg, Janus kinase 1, phosphoinositide-3 kinase delta, and interleukin-1 receptor-associated kinase 4), including degraders that remove scaffolding functions, modulating microRNA, and affecting multiple targets, to name a few. The flexibility afforded by being able to explore all the "chemical space" in this way offers this approach a marked advantage over other modalities. With their advantage in effective targeting, convenience, cost, and diverse modes of delivery, small molecules are here to stay. With more options on the horizon, including genetic modification and editing, artificial intelligence-driven discovery should help small-molecule drugs provide a true and tested modality that we can still rely on, without major negative trade-offs.