Targeted protein degradation is a new therapeutic modality to artificially hijack the components of the UPS to degrade a target protein. Molecular glue degraders destabilize target proteins by bringing them in close proximity to E3 ubiquitin ligases leading to polyubiquitylation and proteasomal degradation of the target protein. So far, the discovery of molecular glues has been serendipitous and lack of reliable technologies to rationally discovery is hampering broad translational efforts. The molecular glue mechanism of action is quite attractive, it enables the targeting of proteins otherwise considered unligandable, since the PROTAC approach effectively requires a defined small molecule ligand.
With tremendous excitement surrounding the field of targeted protein degradation, there is an unmet need for functional assays that can study the effects of molecular glues on ubiquitination of a target(s) and subsequent degradation. Traditional methods such as western blotting and reporter gene assays have been at the forefront of studying target degradation. However, these methods are extremely low throughput, time-consuming, and/or prone to artifacts. LifeSensors has developed high-throughput methods to directly monitor molecular and PROTAC mediated ubiquitylation and degradation of target proteins.