Proteolysis Targeting Chimeras (PROTACs) represent a promising set of drugs that target proteins without an inherent enzymatic activity for proteasomal degradation. Despite all the efforts being invested in PROTAC discovery, progress in developing drugs for clinical use is slow mainly due to the methods (Western blot, gene reporter-based methods) used to screen potential PROTAC drugs. In addition to being time-consuming, immuno-blotting techniques are highly irreproducible. Gene reporter assays are appropriate for use in high-throughput screens (HTS) but require establishing stable cell lines prior to the assay development phase. It also does not provide any information regarding the ubiquitination of the target protein prior to its subsequent degradation. The PROTAC community needs a comprehensive HTS assay that can detect not only the degradation, but also the ubiquitination of the endogenous form of the target protein.