New small molecular drug approvals for 2025: clinical applications, mechanism of action, and chemical synthesis.

Abstract

In 2025, the U.S. FDA approved 46 new drug applications, including 34 new molecular entities and 12 biologics license applications. The new molecular entities include 31 small-molecule drugs and 3 oligonucleotides, while the biological license applications cover monoclonal antibodies, bispecific antibodies, antibody-drug conjugates, and fusion proteins. These newly approved molecules not only feature favorable skeletal structures but also embody the comprehensive achievements of multiple fields, including modern drug discovery, drug synthesis, and the study of pathogenesis. In this review, we comprehensively summarize the clinical indications, mechanisms of action, and synthetic routes of the 31 newly approved small-molecule drugs in 2025, providing a reference for follow‑up drug‑discovery practice.