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Updated: May 2, 2026

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Structure of Class B GPCRs: new horizons for drug discovery
Andrea Bortolato1, Andrew S Doré, Kaspar Hollenstein
1Heptares Therapeutics Limited, Welwyn Garden City, Hertfordshire, UK.
Abstract:
Class B GPCRs of the secretin family are important drug targets in many human diseases including diabetes, neurodegeneration, cardiovascular disease and psychiatric disorders. X-ray crystal structures for the glucagon receptor and corticotropin-releasing factor receptor 1 have now been published. In this review, we analyse the new structures and how they compare with each other and with Class A and F receptors. We also consider the differences in druggability and possible similarity in the activation mechanisms. Finally, we discuss the potential for the design of small-molecule modulators for these important targets in drug discovery. This new structural insight allows, for the first time, structure-based drug design methods to be applied to Class B GPCRs.
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