Eurofins Discovery accelerates Target Protein Degradation drug discovery
Michele Modugno, Scientific Project Leader, michele.modugno@discovery.eurofinseu.com; Olivier Mirguet, Development Project Leader, Olivier.Mirguet@discovery.eurofinseu.com; Jean Bernatchez, Senior Scientist Group leader, Jean.Bernatchez@discovery.eurofinsus.com
Eurofins Discovery, a global leader in providing drug discovery and development solutions, has built a comprehensive toolbox of capabilities to enable programmes in the Targeted Protein Degradation field. With wide-ranging applications for Molecular Glues and PROTACs® (Proteolysis Targeting Chimeras) spanning multiple therapeutic areas, such as oncology, neurodegenerative diseases, and beyond, these approaches hold promise for targeting notoriously challenging proteins that were previously considered “undruggable,” and offer new avenues for treating diseases with enhanced precision and reduced side effects.
Eurofins Discovery’s advanced capabilities in developing Molecular Glues and PROTACs® integrates computational, medicinal and automated synthetic chemistry, molecular and cellular biology, and pharmacology. As a case study, this process is being applied to generate PROTACs targeting the PIM3 kinase and includes:
- Medicinal chemistry-driven precision design of PROTACs® based on known PIM inhibitors as well as hit compounds obtained from an internal HTS campaign.
- Use of a state-of-the-art robotics lab that accelerates PROTAC® preparation by enabling the simultaneous synthesis of multiple compounds in parallel.
- Characterisation and validation of novel PIM3 bifunctional degraders using KINOMEscan®, KinaseProfiler™ and E3scan™ platforms to assess potency and selectivity.
- Use of biophysics methods like Surface Plasmon Resonance (SPR) or MicroScale Thermophoresis (MST) to assess binary (PIM3-PROTAC®) and ternary (PIM3-PROTAC®-E3 ligase) complex formation, as well as establishing the key interaction parameters between PROTACs® and their target proteins, such as the affinity, binding kinetics, residence time and cooperativity factor.
- Cellular assays assessing quantitative protein degradation and translational phenotypic assays (including the BioMAP® and OncoPanel™ Platforms) evaluating pharmacological effects in human cells, determining cellular efficacy, and directing potential clinical applications.
These cutting-edge capabilities in Targeted Protein Degradation position Eurofins Discovery as an ideal collaborator for biotech and pharma partners aiming to develop novel treatment approaches, offering hope for innovative therapies that significantly impact patient care. For more information, visit: www.eurofinsdiscovery.com
