Innovations and Breakthroughs in Bifunctional Molecules

Dear Colleagues,

This Special Issue focuses on bifunctional molecules, a field rapidly redefining the boundaries of "druggability" by bringing countless disease targets once considered "undruggable" within therapeutic reach. Traditional small-molecule inhibitors rely on an "occupancy-driven" mechanism, requiring high-affinity binding to the active site of a target protein to block its function—an approach often ineffective against targets lacking well-defined binding pockets. In contrast, bifunctional molecule technology adopts a novel "event-driven" paradigm. Through sophisticated molecular design, a target protein ligand is covalently linked to an effector function ligand (e.g., an E3 ubiquitin ligase recruiter) via a connector, enabling the recruitment of powerful biological systems (e.g., the ubiquitin–proteasome system, the lysosomal system, etc.) within the body to precisely regulate or eliminate pathogenic target proteins. This Special Issue highlights cutting-edge technologies and intends to feature groundbreaking research on emerging platforms such as PROTAC, molecular glues, LYTAC, AUTAC (autophagy-targeting chimera), and RIBOTAC (RNA-targeting chimera), covering their molecular design, mechanisms of action, and optimization strategies. By gathering insights from leading researchers in the field, we will provide a valuable resource for scientists, drug development experts, and students, fostering collaboration to advance this dynamic discipline and, ultimately, deliver next-generation transformative therapies to patients worldwide. We invite you to contribute to this Special Issue and jointly explore the boundless possibilities of bifunctional molecules.

Dr. Xiaoli Xu
Guest Editor

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