Despite the tremendous promise of PROTACs, their widespread application has been tempered by concerns of off-target effects and related toxicities . Protein degraders have been developed against a variety of clinically relevant protein targets in cancer, such as the androgen receptor and estrogen receptor , with candidates in clinical trials. However, the lack of precise control over their activity has raised concerns . The powerful catalytic nature of PROTACs may lead to uncontrolled degradation of the POIs in both pathological and healthy tissues -leading to broad-scale toxicity. For example, inhibition of BET bromodomains is relatively well tolerated, while complete loss of BRD2 and BRD4 is lethal, which reduces the therapeutic window of dBET1, a PROTAC targeting BET bromodomains . Moreover, the inherent promiscuity of traditional chemistries employed in PROTAC design can result in unintended interactions, leading to unwanted degradation of non-target proteins and contributing to systemic toxicity . As such, there is an urgent need for advanced strategies that can fine-tune the activity of PROTACs, ensuring they are activated with control, without causing collateral damage to the proteome. To this end, the design of stimuli-activatable PROTAC prodrugs has been a promising approach. Such designs feature PROTACs that persist in an inactive-state until activated by endogenous or exogenous stimuli in specific tissues -thus, remaining "silent" elsewhere. PROTAC activation has been induced with click chemistry , light , hypoxia , and reactive oxygen species . However, to our knowledge, there has been no development of a PROTAC 'off' switch, which is important for temporal control to reduce off-target activity.