Automated Profiling of PROTAC-Induced Cereblon Neosubstrate Degradation Using Simple Western

Targeted protein degradation by PROTACs is an exciting new therapeutic modality with the potential to expand the 'druggable' proteome to new target proteins called neosubstrates. PROTAC protein degradation typically involves the E3 ligase cereblon to ubiquitinate a neosubstrate that is subsequently degraded by the proteasome. However, cereblon protein degradation is often measured by Western blot, which is poorly reproducible and has a lengthy, manual workflow, slowing PROTAC cereblon drug development.

Here, we present data showing the power of automated Simple Western™ platforms to screen panels of Degrader and IMiD compounds in order to quantify cereblon protein degradation activity. We demonstrate the time savings achieved by automating cereblon protein degradation assays as well as Simple Western's ability to accurately quantify the PROTAC cereblon degradation of protein neosubstrate with DC₅₀ and D_max values.