Associate Director Astex Pharmaceuticals, United Kingdom
Abstract: Astex has successfully applied its proprietary Fragment-Based Drug Discovery (FBDD) platform to generate multiple new drug candidates that are progressing in clinical development. The FBDD approach utilizes X-ray crystallography, as well as a variety of other biophysical techniques such as NMR, SPR, ITC, and DSF, to identify hits and develop small molecules. Additionally, Astex has established a state-of-the-art cryo-EM facility, which has emerged as another powerful structural biology technique that is expected to accelerate the discovery and development of new drugs that target integral membrane proteins and multi-protein complexes - target classes that have traditionally been difficult to study using X-ray crystallography.
These biophysical techniques provide critical insights into the structure, dynamics, and function of proteins, as well as for characterizing protein-ligand interactions. The production of high-quality, pure, and functional proteins is crucial for the success of the FBDD/SBDD process. While the specific protein production requirements depend on the biophysical technique being used, there are some general considerations that apply across methods. In this talk, I will share our experience and case studies on the expression, purification, and biophysical characterization of some challenging drug targets.