Small molecule degraders such as PROteolysis TArgeting Chimeras (PROTACs) and molecular glues are new modalities for drug development and important tools for target validation. When appropriately optimized, both modalities lead to proteasomal degradation of the protein of interest (POI). Due to the complexity of the induced multistep degradation process, controls for degrader evaluation are critical and commonly used in the literature. However, comparative studies and evaluations of cellular potencies of these control compounds have not been published so far. Here, we investigated a diverse set of ubiquitin pathway inhibitors and evaluated their potency and utility within the CRBN and VHL-mediated degradation pathway. We used the HiBiT system to measure the level of target rescue after treatment with the control compounds. In addition, the cell health was assessed using a multiplexed high-content assay. These assays allowed us to determine nontoxic effective concentrations for control experiments and to perform rescue experiments in the absence of cellular toxicity.