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. 

Advantages of Choosing LifeSensors for your Molecular Glue Drug Discovery

  • Study Molecular Glue mediated Ubiquitination and Degradation simultaneously
  • High through-homogenous ubiuquitnation assays to screen for molecular glues 
  • Complete suite of validation studies to establish binding, ternary complex formation, and cellular degradation
  • Experience with novel E3 ligases – ~30 E3 ligases amenable to PROTAC discovery
  • Proteomics to characterize protein degradation – establish selectivity

With a deep and diverse expertise in medicinal chemistry, biochemistry, and cell-biology specializing in ubiquitin based drug discovery for the last 15 years, LifeSensors is proud to offer efficient methods to accelerate your discovery of novel molecules facilitating targeted protein degradation. We offer our degrader discovery services starting from design and synthesis of novel PROTACs and molecular glues, to monitoring binding to target and E3 ligases (biochemical and biophysical), including functional ubiquitination and degradation assays in cells. Monitoring ubiquitylation in vitro permits rapid screening of compound libraries and allows simplification of the medicinal chemistry approach to rationally design potent molecules. Your biochemists can focus on new targets as LifeSensors will translate its core technologies for in vitro and cellular screens.