Fluorine-containing FDA-approved small-molecule drugs in 2025: significance, synthetic insights, and therapeutic applications

Abstract

Fluorine has been widely incorporated into small-molecule drugs as an effective strategy to modulate metabolic stability, lipophilicity, target interactions, and overall pharmacokinetic profile. As a result, fluorine-containing compounds remain well represented among newly approved therapeutics across a broad spectrum of disease areas; notably, in 2025, 14 of the 29 small-molecule drugs approved by the U.S. Food and Drug Administration (FDA) contained at least one fluorine atom, underscoring the continued relevance of fluorine in contemporary drug design. This annual review highlights the role of fluorine in modern medicinal chemistry by summarizing FDA-approved fluorine-containing small-molecule drugs in 2025. The review examines their therapeutic indications, molecular targets, and structural features, and outlines representative synthetic strategies used in their preparation. Overall, this review provides an updated perspective on the continued importance of fluorine chemistry in modern drug discovery and development.