Roundtable Discussion: Building in High Binding Affinity & Selectivity into GPCR Ligands Using Structure-Guided & Biophysical Approaches
- What are the main challenges in overcoming GPCR ligand promiscuity, and how can we ensure selectivity when overlapping signalling pathways risk off-target effects and reduced therapeutic precision?
- How can allosteric modulators that bind to alternative receptor sites be leveraged to achieve more refined control of receptor activity and significantly improve specificity?
- In what ways can high-resolution structural data inform the rational design of GPCR ligands, helping to optimise binding interactions and accelerate the development of highly selective therapeutic agents?
- Can we optimise binding kinetics so that ligands have a long residence time in the receptor to achieve higher efficacy?