Groundbreaking Technique Speeds Up Drug Design for Ion Channel Disorders

An international research team has developed a pioneering technique that promises to accelerate drug design for diseases linked to ion channels, crucial proteins found in cell membranes. This study, led by the Institute of Chemical Research, a joint center of the University of Seville and the Spanish National Research Council, alongside partners from the University of East Anglia and the Quadram Institute, was published on November 15, 2025, in the Journal of the American Chemical Society.

Ion channels play a vital role in regulating the passage of ions into cells, influencing various physiological processes from nerve transmission to immune responses. Their dysfunction is linked to a wide range of ailments, including psychiatric disorders and certain cancers. Traditionally, studying drug interactions with these proteins required isolating them in a complex process that could alter their behavior. The new technique utilizes nuclear magnetic resonance, allowing researchers to observe these interactions in living cells, thus providing more accurate biological data.

“This method significantly simplifies and speeds up the study of drug interactions,” said Jesús Angulo from the Institute of Chemical Research. The new approach enables experiments to be conducted in under an hour, eliminating the need for intricate protein purification steps. Researchers believe this innovation could standardize structure-activity studies, which examine how the chemical structure of a molecule impacts its pharmacological effect.

The technique has already shown promise in targeting P2X7 receptors, which are relevant for conditions such as depression and certain autism spectrum disorders. “We can identify which parts of the drug interact with the protein in real-time, allowing us to optimize these interactions,” explained Serena Monaco, a researcher at the Quadram Institute. This insight is crucial for developing more effective and specific therapeutics.

In addition to the experimental advancements, the team employed software developed at IIQ-CSIC-US to integrate their findings with three-dimensional models of drug-receptor interactions generated through bioinformatics. This validation process confirms which computational models align with laboratory observations.

“The drug-protein interaction is like a lock and key: the membrane protein acts as the lock while the drug is the key,” Angulo elaborated. “Finding the right key is just the beginning; we also need to understand how to insert it effectively.” The ability to validate computer models using real-time observations from living cells marks a significant shift in the drug development landscape.

The implications of this new technique extend beyond ion channels, opening avenues for research in areas such as neurological, cardiovascular, and metabolic diseases. The potential for accelerated drug discovery could have a profound impact on the development of therapies for various conditions that currently lack effective treatment options.

For more detailed information, refer to the article by Serena Monaco et al., titled “On-Cell Saturation Transfer Difference NMR Spectroscopy on Ion Channels: Characterizing Negative Allosteric Modulator Binding Interactions of P2X7,” published in the Journal of the American Chemical Society. The findings underscore the innovative strides being made in the realm of pharmacological studies and their promise for future drug development.