Small-molecule-based therapeutics play a vital role in drug discovery. These molecules are preferred owing to their oral bioavailability, ease of tuning the physicochemical properties, and broad target accessibility. In this review article, we have explored the small molecules approved by the US Food and Drug Administration (USFDA) in 2025. Through the analysis, we found 44 drug approvals, out of which 30 candidates were approved as new molecular entities (NMEs), while the remaining 14 were approved in the category of biologics, including 10 approved as biosimilars. Considering the therapeutic area distribution of 30 NMEs, 28 drugs are approved as monotherapy, with 10 drugs as anticancer agents, 4 drugs for genetic disorders, 2 drugs each for the conditions of immunological, respiratory, ophthalmic, and endocrine disorders, along with the treatment of cardiac and infectious diseases. The structural diversity analysis revealed that 29 approved drugs were aromatic (azaheterocycles) in nature, and 13 drugs possess at least one stereogenic center. Considering the elemental diversity, the near-universal presence of nitrogen in the form of amines, amides, and as a heteroatom, followed by the oxygen atom. Additionally, the prevalence of 3- or 4-membered carbocyclic or heterocyclic rings was found in five approved drugs. For metabolism, most drugs rely on CYP3A-mediated metabolism, primarily through CYP3A4, CYP2D6, and CYP2C8. Collectively, the analysis and compilation of the drugs presented are expected to provide practical insights and offer guidance to medicinal chemists, biologists, and scientists associated with current drug-discovery paradigms, making continuous strides for future medicinal chemistry innovations and evolutions.
Rao et al. (Mon,) studied this question.