Biophysics for Successful Drug Discovery Programs

Biophysics has an essential role in identifying and characterizing small molecules and biologics for targets of interest throughout the drug discovery process. In purpose-built laboratory space using state-of-the art equipment, our experts offer integrated custom biophysical solutions, adapted to client needs. With a comprehensive understanding of biophysics methodology, our team provides precise interpretation of data in addition to customized guidance for biophysics cascade strategy and complementary approaches.
 
Using high-quality soluble and membrane proteins produced by Eurofins DiscoverX® and Eurofins CALIXAR, biophysics can be applied from hit finding to candidate selection, for a variety of different modalities: fragments, small molecules, targeted protein degraders, RNA/DNA binders, aptamers, peptides and biologics. We support clients with complex screening solutions for various stages of drug discovery programs, available as individual LeadHunter® services, as well as part of our integrated DiscoveryOne™ program.
 

 

Affinity-based screening for Hit Finding

Biophysical methods with direct target-binding are a breakthrough for early drug discovery. For the first time, using High Throughput Spectral Shift (HT-SpS), binders can be identified in large-scale, single-dose screening projects using a direct biophysical measurement. It provides a valuable alternative to existing solutions, such as Affinity-Selection Mass Spectrometry (AS-MS) and DNA-encoded library (DEL). HT-SpS makes high-throughput, site-agnostic binding approaches achievable with a very small amount of the tested target, no data deconvolution, and with no need of compound multiplexing.
 
Alternatively, Thermal Shift Assay (TSA) also allows for large affinity-based screening, with the added advantage of simplified assay development and the possibility to distinguish between types of binders (i.e. stabilizers, destabilizers or no effect).
 
For high-throughput analysis, Genedata Screener® can efficiently analyze large data sets. By applying data normalization or providing outlier detection and quality control, it enhances the reproducibility and reliability for decision-making in binder identification.

Fragment-based Screening (FBS)

Biophysical methods are well suited for fragment-based screening as they are sensitive enough to detect weak binding and reliable enough to avoid false positives. A variety of methods can be applied to fragment screening, such as Surface Plasmon Resonance (SPR), microscale thermophoresis (MST), Spectral Shift (SpS) or TSA. With an increasing number of compounds identified through these methods, fragment-based drug discovery (FBDD) will play an essential role in target-based drug discovery.

Biophysics for Hit Confirmation, Hit-to-lead and Lead Optimization

Our experts support orthogonal assays for screening projects, follow-up strategies for hit profiling, Mechanisms of Actions (MoA) insights as well as Structure-Activity Relationship (SAR) for MedChem analysis. Biophysics is especially relevant for compound ranking as it is a highly sensitive approach in determining the affinity of the interaction (dissociation constant, KD), binding kinetics (Kon and Koff), residence time and thermodynamic profile for novel chemical leads.

Biophysics for Ternary Complex Formation Characterization

Biophysics methods can measure the binding affinity, kinetics and thermodynamics parameters of protein-targeted degraders. It enables the study of dynamic, transient interactions such as the formation of ternary complexes. Understanding binding cooperativity between degrader, target protein and E3 ligase is critical for optimizing the design of proximity-induced modalities. Biophysics assays can be adapted for high throughput screening to identify effective degraders such as molecular glues from a library of compounds.

Macromolecule Characterization

Regardless of whether you are working on antibodies, biosimilars, or cell and gene therapies, biophysical characterization is a powerful tool to profile drug function, activity and stability. The benefit of working with our team means our experts can monitor conformational integrity, help you understand the relationship between protein structure and stability, and provide insight into protein aggregation in solution.
 
These key characterizations provide valuable information on antibody-drug manufacturability, and an early CMC assessment will ensure that your biologic has the best chance of development and clinical success.
 
From hit profiling through lead optimization and candidate selection: Defining the mechanism of action through biophysical characterization of your biologic ensures your next blockbuster biotherapeutic is safe and efficacious.

Our Broad Range of Biophysics Assays

Explore our portfolio of ready-to-use optimized assays or leverage Eurofins Discovery’s expertise for custom assay projects. We currently offer:

• Affinity-based screening for binder identification with Eurofins Discovery’s library or our client’s library
• Fragment-based drug discovery (FBDD) with Eurofins Discovery’s fragment library or our client’s library
• Hit profiling (binding characterization of small molecules with POI)
• Mechanisms of action (Identification of allosteric binders)
• Ternary complex formation with Proteolysis-targeting Chimeras (PROTACs)
• Binding characterization with Molecular Glues (MG)
• Compound solubility
• Protein characterization (aggregation, buffer selection, stability)
• Biologic characterization (stability, aggregation, formulation, etc.)
• Biologic binding studies
• Epitope binning

Biophysical Technologies

Eurofins Discovery’s cutting-edge biophysical platforms: