Reactive oxygen species-responsive Pre-PROTAC for tumor-specific protein degradation

By introducing a reactive oxygen species (ROS) triggered leaving group (arylboronic acid) to the parent PROTACs, ROS-responsive Pre-PROTACs were designed and evaluated. Pre-PROTAC (7) efficiently degraded the target protein BRD3 according to ROS levels. Our research provides an effective approach to control PROTAC activation by the endogenous ROS-related microenvironment.