To evaluate the ability of SIM1-6 trivalent compounds to induce intracellular degradation of BET proteins, we first treated human HEK293 cells for 4h at 1µM and assessed protein levels by western blot. Profound degradation across BET proteins was observed with VHL-based SIM1-SIM3, while minimal to partial degradation was observed with CRBN-based SIM4-SIM6 (Fig. ). To confirm the results we next used live cell continual luminescent monitoring of CRISPR/Cas9 endogenously tagged HiBiT-BRD4 in HEK293 cells over 24h . Faster rates of BRD4 degradation accompanied by greater maximal degradation levels were seen with SIM1-SIM3 as compared to the slower and partial loss observed with SIM4-6 (Extended Data Fig. ).