Fragment-based drug discovery is a powerful approach in drug discovery, applicable to a wide range of targets. This method enables the discovery of potent compounds that can modulate target functions, starting from fragment compounds that bind weakly to the targets. While biochemical, biophysical, and cell-based assays are commonly used to identify fragments, 19F-NMR spectroscopy has emerged as a powerful tool for exploring interactions between biomolecules and ligands. Because fluorine atoms are not naturally present in biological systems, 19F-NMR serves as a sensitive method for fragment screening against diverse targets. Herein, we reviewed the applications of 19F-NMR in fragment screening, highlighting its effectiveness in identifying fragments that bind weakly to various targets such as proteins and RNA. The accumulated evidence suggests that 19F-NMR will continue to be a crucial tool in drug discovery.
Keywords: 19F-NMR; drug discovery; fragment screening; fragment-based drug design; in-cell 19F-NMR.