Uncovering GPCR heteromer-biased ligands

The formation of complexes involving different G-protein-coupled receptors (GPCRs) is now an established phenomenon, termed heteromerization. The relevance of higher order structures, in particular heteromerization, has been demonstrated by differential pharmacology displayed by GPCR heteromers compared to monomers/homomers of the respective constituent receptor units. The concepts of heteromerization and heteromer-selective/biased ligands introduce exciting opportunities for enhancing signal specificity and therefore have the potential to play a crucial role in future drug discovery.