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 for exploitation of the cell’s own degradation machinery (Ubiquitin proteasome system) to degrade target proteins. Validation of a novel target’s ability to degrade with subsequent observation of the predicted phenotype is crucial for PROTAC drug discovery. At LifeSensors, we offer a comprehensive overview of endogenous target protein expression, generate cell lines with a degrader tag (dTAG, BromoTAG®) on target protein of interest and induce selective degradation with TAGged protein of interest that can elucidate the role of the target in physiological function or a disease mechanism to produce a relevant phenotype. Successful validation of a target followed by the design of chemical modulators like PROTACs that can selectively modulate the endogenous target is largely considered direct evidence of TPD campaign.
Service Highlights
- Validate Target expression levels in relevant cellular models for exploring TPD approach
- Validate role of target in physiological function and disease mechanism
- Dedicated TPD team with more than 20 years of experience in UPS related drug discovery