New Technique Speeds Drug Design Targeting Ion Channels

An international research team has unveiled a groundbreaking technique that significantly accelerates the design of drugs targeting ion channels, proteins closely linked to a variety of diseases, including psychiatric disorders and different forms of cancer. This innovative approach, developed by the Institute of Chemical Research, a collaboration between the University of Seville and the Spanish National Research Council, was published in the Journal of the American Chemical Society on November 15, 2025.

Ion channels are integral membrane proteins that control the flow of ions into and out of cells, playing crucial roles in various physiological processes such as nerve transmission, muscle contraction, and immune responses. Dysfunction in these channels is associated with numerous medical conditions, making them prime targets for therapeutic intervention.

Revolutionizing Drug Interaction Studies

Traditionally, the study of how drugs interact with ion channels required isolating these proteins, a complex process that could alter their natural behavior. According to Jesús Angulo from the Institute of Chemical Research, the new technique employs nuclear magnetic resonance (NMR) to study these interactions in living cells, yielding more relevant biological insights.

“This technique is faster, more cost-effective, and simpler, as it removes the need for extensive protein purification and manipulation,” Angulo stated. The researchers believe this method could establish a new standard in structure-activity relationship studies, which explore how a molecule’s chemical structure influences its pharmacological effects.

Broader Implications for Multiple Diseases

The technique has been successfully tested on P2X7 receptors, which are therapeutic targets for conditions such as depression, certain autism spectrum disorders, and some cancers. Leanne Stokes of the University of East Anglia emphasized the potential of this method: “Our technique could significantly accelerate the development of drugs targeting ion channels and other membrane proteins, opening new avenues for research in neurological, cardiovascular, metabolic, and oncological diseases.”

Furthermore, the researchers utilized software developed at IIQ-CSIC-US to integrate their experimental findings with three-dimensional models of drug-receptor interactions, generated through bioinformatics. This advancement allowed them to validate which computational models aligned with their laboratory observations.

“The interaction between drug and protein can be likened to a lock and key: the membrane protein is the lock, and our drug is the key,” Angulo explained. “Identifying the correct key and determining how to insert it for optimal function is crucial.” He further noted that bioinformatic models play a vital role in drug design and that validating three-dimensional computer-generated models in living cells signifies a transformative approach in developing drugs aimed at these proteins.

This research not only enhances the understanding of drug interactions but also holds promise for more effective and targeted treatments for a range of diseases, marking a significant step forward in pharmacological studies.

For further details, refer to the study: Serena Monaco et al, “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.