Modulating proteins beyond active sites: fragment-based drug discovery approach

Fragment-based drug discovery (FBDD) is a powerful approach for identifying novel chemical starting points and uncovering previously unknown ligandable sites on proteins. Because fragment hits typically bind weakly, sensitive biophysical methods are essential for their detection and characterization. In this presentation, I will focus on the use of surface plasmon resonance (SPR) for fragment screening and hit validation. I will then illustrate how fragment screening can reveal new opportunities for protein modulation using the example of allosteric kinase inhibitors. Finally, I will introduce the emerging field of induced proximity and molecular glues and discuss how fragment-based approaches may contribute to the discovery of compounds that modulate protein-protein interactions and enable novel therapeutic mechanisms.