We are hosting our next Early Academic Talks session this month on Thursday 30th April. This is a great opportunity for Early Career Researchers (ECRs) to network and learn about the research at Imperial in a friendly and informal environment.
Modelling G protein biased agonism using glucagon-like peptide-1 receptor (GLP-1R) C-terminal modifications
Biased GLP-1R agonists such as tirzepatide and orfoglipron demonstrate better clinical outcomes than earlier monoagonists like semaglutide, yet the full impact of biased agonism remains difficult to study due to variations in how different ligands behave pharmacokinetically. To address this, targeted mutations introduced into the receptor’s C-terminal tail generate a receptor-based model that recapitulates G protein biased agonism, enabling precise characterisation of this signalling phenomenon without the need for ligand modifications.