Discovery of Potent and Brain-Penetrant Inverse Agonists for GPR61, an Orphan G Protein-Coupled Receptor - PubMed
4 hours ago
- #inverse agonists
- #GPCR
- #GPR61
- GPR61 is an orphan G protein-coupled receptor (GPCR) expressed in the pituitary gland and brain regions regulating appetite.
- Research suggests GPR61 as a potential therapeutic target for modulating appetite and body weight.
- A class of potent, selective, and brain-penetrant GPR61 inverse agonists has been discovered.
- Cryogenic electron microscopy reveals that these inverse agonists bind to an intracellular allosteric pocket.
- The binding disrupts GPR61's interactions with G protein, eliminating its constitutive activity.
- This represents a novel mechanism of action for GPCR inverse agonism.