Molecular ‘glues’ and ‘bumpers’ on receptors can bias signalling inside the cell

Compounds that bind to the intracellular core of G-protein-coupled receptors can encourage interactions with some G proteins and prevent them with others, leading to a switch in downstream signalling pathways. Rational design of such core-targeted compounds could be used to find small molecules that modulate this diverse superfamily of receptors. Small molecules that bind to G-protein-coupled receptors’ intracellular pockets can be designed to have pathway-selective effects.