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. This allows to exploit cell’s own degradation machinery (Ubiquitin proteasome system) to degrade target proteins. PROTAC approach has shown great promise to degrade proteins that are previously deemed extremely difficult to target but their expansion to vast undruggable proteome remains elusive due to lack of efficient workflow to understand structure-activity relationship and rationally design potent PROTACs. LifeSensors offer a comprehensive evaluation of PROTAC mediated ubiquitination and degradation using traditional western blotting, reporter gene assays (fluorescent proteins, HiBiT) and LifeSensors’ high throughput ubiquitination and degradation assays. Our targeted protein degradation team has a strong track record in developing preclinical PROTAC programs starting with identification of ligands for target, ligands for E3 ligases, designing model PROTACs, establishing ubiquitination, degradation, and lead optimization. During the optimization stage we offer collaboration with chemistry teams to rationally design a PROTAC that has superior ubiquitination and degradation profiles that can translate into reliable clinical candidates.
- Establish PROTAC activity by monitoring ubiquitination and degradation using high throughput screening
- 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 based on extent of ubiquitination
- Target exploration and validation
- Dedicated TPD team with more than 20 years of experience in UPS related drug discovery