ROS-Mediated Controllable Targeted Protein Degradation: Progress and Reflections

In recent years, controllable targeted protein degradation has emerged as an innovative chemical tool and therapeutic strategy for drug discovery. As a spatiotemporally precise alternative to conventional PROTACs, ROS-mediated controllable targeted protein degradation has attracted growing attention. This Perspective outlines the design principles, mechanisms, and representative advances of photodynamic, photothermal, and sonodynamic ROS degraders. We critically assess their druggability advantages, clinical translation barriers and limitations, while providing forward-looking insights into rational design and therapeutic applications. We aim to provide a medicinal chemistry-focused guidance for the development of next-generation controllable targeted protein degradation platforms.