Hafez-Ghoran_2025_Bioorg.Med.Chem_125_118212

Among the various multiple nuclear magnetic resonance (NMR) approaches available, saturation transfer difference (STD) NMR spectroscopy has proven to be highly effective in identifying potential binders (ligands). Researchers increasingly recognize the integration of STD-NMR data with ligand-receptor docking studies as a reliable approach for elucidating binding modes at an atomic level. Beyond drug discovery, STD-NMR provides significant contributions to fundamental biological interactions. This review compiles natural and synthetic molecules identified as potential binders through STD-NMR spectroscopy for specific targets associated with chronic diseases, including cancers, neurological disorders, infectious diseases, and others. In cancer research, STD-NMR has helped identify ligands targeting B-cell lymphoma 2, fucosyltransferase 2, ubiquitin ligase, RNA-binding protein HuR, microtubules, cadherins, and urease. Similarly, various synthetic and natural scaffolds have been identified as modulators of enzymes and proteins implicated in neurological disorders, such as acetylcholinesterase, butyrylcholinesterase, amyloid beta, and alpha1A- and alpha1B-adrenoceptors. This review also highlights potential identified hits for validated and emerging drug targets in infectious and other diseases.