PROTAC & DUBTAC Drug Discovery

PROTACs (Proteolysis-targeting chimeric molecules) artificially hijack the components of the UPS (Ubiquitin Proteasome System) to degrade a target protein, founding the concept of PROTAC Drug Discovery. PROTAC drugs are hetero-bifunctional small molecules that contain two functional ligands connected via a linker; one ligand binds to a target protein and the other ligand binds to an E3 ligase. Bringing these two entities into proximity theoretically leads to polyubiquitylation and proteasomal degradation of the target protein. However, given the complexity this scenario does not always play out, and the PROTAC discovery platform faces several challenges.

With tremendous excitement surrounding the field of targeted protein degradation, there is an unmet need for functional assays that can study the effects of PROTACs on the ubiquitination of a target(s) and subsequent degradation. Traditional methods such as western blotting and reporter gene assays have been at the forefront to study PROTAC mediated degradation. However, these methods are extremely low throughput, time-consuming, and/or prone to artifacts. LifeSensors has developed high-throughput methods to directly monitor PROTAC mediated ubiquitylation and degradation of target proteins.

Advantages of Choosing LifeSensors for your PROTAC Drug Discovery

• Study PROTAC mediated Ubiquitination and Degradation simultaneously
• 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 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, to monitoring PROTAC binding to target and E3 ligases (biochemical and biophysical), including functional ubiquitination and degradation assays in cells. PROTAC-mediated 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 PROTAC targets as LifeSensors will translate its core technologies for in vitro and cellular PROTAC screens.