Liang Chang, Min Wang, Huijie Zhang, Zhen Li, Zixuan Song, Lijie Zhao, Fengli Jiang, Yi-Xiang Wang, Quan Yuan
In 2025, the U.S. Food and Drug Administration (FDA) continued to advance therapeutic innovation by approving a diverse range of novel drugs. According to the FDA's 2025 Novel Drug Approvals list, 46 new drugs received approval, including both new chemical entities such as Ziftomenib, Sevabertinib, Zoliflodacin, and Gepotidacin, as well as new biologics. These approvals cover a wide range of therapeutic areas, including oncology, rare genetic diseases, infectious diseases, cardiovascular diseases, and immunomodulation. A significant proportion of the approved products navigated accelerated or priority review pathways, reflecting their potential impact on unmet medical needs. This review provides a comprehensive overview of the synthetic routes and clinical applications of FDA-approved small-molecule drugs in 2025, aiming to inspire future development in drug discovery.