Photocleavable PROTACs as tools for dynamic regulation of protein function

Proteolysis-targeting chimeras (PROTACs) have emerged as valuable tools for targeted protein degradation. However, conventional designs generally lack mechanisms for temporal regulation. In this study, we explored photocleavable PROTACs incorporating a nitrobenzyl linker, aiming to achieve light-triggered inactivation of BET protein degradation. Docking simulations indicated that the linker did not disrupt the formation of the ternary complex, and LC-MS/MS analyses indicated that photocleavage occurred rapidly within cells. Cellular experiments demonstrated that the compounds promoted efficient degradation of the BET protein at low concentrations, and recovery assays with UV irradiation indicated that protein expression could be restored after transient depletion. These results suggest that photocleavable PROTACs offer a practical approach to controlling degradation with temporal precision and may provide useful chemical biology tools for investigating the dynamic functions of BET proteins.