The 2025 FDA Small-Molecule Portfolio: Clinical Applications, Synthetic Approaches, Challenges, and Solutions

In 2025, the U.S. Food and Drug Administration (FDA) approved 46 new drugs comprising 31 small-molecule entities. These approvals represent significant milestones in the evolution of privileged structures and novel mechanisms of action, serving as invaluable leads for the development of next-generation therapeutics with enhanced efficacy. This article reviews the synthetic routes and clinical indications of these newly marketed drugs, highlighting their significance in the current pharmaceutical landscape.