PROTACs (PROteolysis TArgeting Chimeras) are heterobifunctional molecules with a distinct ligand that targets a specific E3 ligase which is tethered by another ligand specific for the target protein, using an optimized chemical linker. Current PROTAC discovery heavily relies on monitoring the Ternary complex formation using biophysical and biochemical approaches like TR-FRET proximity ligand assays and SPR that does not monitor true function of PROTAC i.e., PROTAC mediated ubiquitination. Designing PROTACs that harness the protein’s intrinsic properties, such as exposed lysines that in turn result in efficient ubiquitination, is crucial to develop potent degraders. Most current PROTACs utilize only a few E3 ligases, which ultimately hinders the vast expansion of the undruggable proteasome. LifeSensors offers a comprehensive evaluation of PROTAC mediated ubiquitination and degradation using customized assays. The in vitro ubiquitination platform was designed to monitor multiple variants of PROTAC with variable linkerology, exit vectors, variable ligands for an E3 ligase, or targets to evaluate the best combination that results in robust ubiquitination. We offer collaboration with chemistry teams to rationally design PROTACs that have superior ubiquitination efficiency that can translate into superior degradation in vivo.
Service Highlights
- Monitor PROTAC activity by monitoring ubiquitination, with the target of your choice in HTS format.
- Accurately establish rank order potencies to guide medicinal chemists for reliable SAR.
- Screen for superior E3 ligases for novel targets based on ubiquitination potential.
- Rationally discover and design molecular glues.