Traditional targeted drug discovery focuses on modulating protein activity through catalytic active sites or regulatory sites of disease-modifying targets. However, 80% of human proteins lack an accessible binding pocket and remain largely undruggable. Targeted Protein Degradation overcomes these limitations by exploiting the cell’s own proteasomal clearance mechanisms reliant on E3 ubiquitin ligases.
In contrast to traditional small molecule inhibitors, bifunctional degraders can now target previously undruggable targets, such as transcription factors, scaffold proteins and other non-enzymatic proteins, can be tissue-selective and are designed to have reduced off-target effects.
Eurofins Discovery Targeted Protein Degradation portfolio includes comprehensive biochemical, cell-based, and biophysical solutions along with chemistry and translational support to enable discovery and development of novel protein degraders.
- Characterize and validate the warhead end of novel bifunctional degraders using KINOMEscan™, BROMOscan™, BCL2scan, STAT SH2 ligand binding assays or custom-made binding assays.
- Identify and characterize novel, potent, and selective ligands that bind and reprogram E3 ligase substrate specificity for Targeted Protein Degradation using E3scan™ ligand binding assay platform.
- Quantify changes in endogenous protein levels in disease-relevant cell models using SPRINTer™ protein turnover cell-based assays.
- Perform compound-target engagement with InCELL cell-based target engagement assays.
- Determine the affinity of the interaction, binding kinetics, residence time, ternary complex formation, thermodynamic profile and positive cooperativity for novel leads using custom biophysical assays.
- Streamline compound design, SAR development, virtual screening and compound synthesis by partnering with expert computational, synthetic and medicinal chemistry teams.
- Elucidate novel mechanisms of action and determine cellular consequences of degrader activity in human primary cell models including the BioMAP® and OncoPanel® Platforms.
Broaden drug discovery efforts to include previously undruggable targets with Eurofins Discovery’s Targeted Protein Degradation solutions.
Figure. Eurofins Discovery’s Targeted Protein Degradation Capabilities
