Allosteric Modulators: Unlocking New Dimensions from Molecular Discovery to Therapeutic Potential

Dear Colleagues,

Allosteric modulation is a promising and increasingly indispensable strategy in contemporary drug discovery. In contrast to orthosteric ligands that engage the primary active site, allosteric modulators exert their influence through topographically distinct binding sites, enabling modulation of receptor conformation, signaling bias and receptor activation kinetics in a finely tuned manner. This alternative mode of regulation offers the potential for enhanced subtype selectivity and a broader therapeutic window. This Special Issue aims to showcase the latest advances in the discovery, characterization and therapeutic exploitation of allosteric modulators across a diverse range of medical conditions and diseases. We welcome original research articles, reviews, communications, and perspectives that explore:

• Identification and characterization of novel allosteric binding sites
• Protein–ligand interactions beyond the active site
• Modulation of isoform selectivity and signal bias
• Structure-based designs of allosteric modulators
• Allosteric modulation of GPCRs, kinases, ion channels and other pharmacological targets
• Integration of allosteric anchoring strategies into PROTACs, LYTACs and other heterobifunctional technologies
• Synergistic or cooperative interactions between orthosteric and allosteric sites

By bringing together cutting-edge studies from medicinal chemistry, structural biology, pharmacology and computational chemistry, this Special Issue seeks to illuminate how allosteric modulation continues to reshape our understanding of ligand-target engagement and to catalyze the development of next-generation therapeutics.

Dr. Changho Han
Dr. Lisa Barbaro
Dr. Kwangho Kim
Guest Editors

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