Scientists from the University of Seville and international partners have introduced a rapid analytical technique that could significantly accelerate the design of new drugs targeting ion-channel proteins, which play central roles in a wide range of diseases. The findings are reported in the Journal of the American Chemical Society.
Ion channels are key regulators of electrical and chemical communication in cells. Because their dysfunction is linked to neurological disorders, immune-related conditions, metabolic diseases, and several cancers, they are considered high-value drug targets. However, developing medicines against these proteins has been slow, largely because researchers must isolate and purify the channels—steps that are technically demanding and often distort how the proteins behave in real biological environments.
The newly developed approach overcomes this barrier by using nuclear magnetic resonance (NMR) to track drug–protein interactions directly inside living cells. This allows scientists to observe how candidate molecules actually bind to their targets under realistic conditions. The experiments can be completed in under an hour, offering a faster and more economical route to screening and optimizing drug candidates.
To demonstrate its potential, the team applied the method to P2X7 ion channels, important therapeutic targets in depression, certain autism spectrum disorders, and oncology. The technique revealed which portions of a drug molecule attach to specific regions of the receptor, giving researchers precise guidance for modifying chemical structures to improve potency and specificity.
Advanced software developed at the Institute of Chemical Research was used to match the experimental observations with three-dimensional computational models of drug–receptor binding. This validation step helps identify which predicted molecular “fits” are realistic, strengthening the reliability of drug-design workflows.
According to the authors, the combination of cell-based NMR and computational modeling introduces a more efficient path for structure-activity studies, potentially shortening the time needed to progress drug candidates from concept to preclinical testing. They anticipate broad applications across drug development for neurological, cardiovascular, metabolic, and cancer-related conditions.