Join us in-person in San Francisco, CA at Human PK and Dose Prediction for Small Molecules. Learn more about our involvement in the event below.
Evotec At the 11th Novalix Conference
Biophysical Approaches for Advancing GPCR Targeted Drug Discovery (OC09)
Edoardo Fabini (1), Alicia Churchill-Angus (1), Sara Crespillo Torreno (1), Erika Griss (1), Florian
Krieger (2), Cedric Fiez-Vandal (1), Jay Bertrand (3), James Errey (1)
1) Evotec, 114 Innovation Drive Milton Park, Abingdon OX14 4RZ, United Kingdom
2) Evotec Essener Bogen 7 · 22419 Hamburg, Germany
3) Evotec, 303B College Rd E, Princeton, NJ 08540, United States
G protein-coupled receptors (GPCRs) are critical targets in drug discovery, but their structural complexity and dynamic nature pose significant challenges for their characterization outside of their cellular environment, a critical aspect of advancing compounds into drug candidates [1].
Evotec has developed an advanced biophysical platform for the comprehensive characterization of GPCRs, which includes the optimization of construct design, protein expression, purification, and assay development.
A key advancement in our platform is Grating-Coupled Interferometry (GCI), a technology that enables high-resolution, label-free analysis of binding affinities and kinetics of receptor-ligand interactions. Over the past few years, Evotec has successfully applied this platform to study multiple GPCRs from both Class A and Class B, supporting agonist and antagonist drug discovery programs. GCI is helping us support these programs by dissecting heterogeneous interactions and accelerating the thermodynamic profiling of compounds binding. It also supports computational modeling by enabling the mapping of binding sites via rationally designed mutant proteins. By integrating biophysical techniques with structural analyses, we accelerate the identification of lead molecules targeting GPCRs.
This work will highlight our approach to compound profiling and fragment screening and will present several case studies where Evotec’s platform was leveraged to discover and characterize GPCR binders. It will also demonstrate how coupling affinity-selection mass spectrometry (AS-MS) with GCI can expedite the screening of large compound libraries and identify sub-micromolar hit compounds as a starting point for hit optimization campaigns.
Presented by Edoardo Fabini, PhD, Principal Scientist, Protein Sciences
Date & Time: Thursday, 22 May, 2025 at 09:35am
