Structure of Class B GPCRs: new horizons for drug discovery |
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Authors: | Andrea Bortolato Andrew S Doré Kaspar Hollenstein Benjamin G Tehan Jonathan S Mason Fiona H Marshall |
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Affiliation: | Heptares Therapeutics Limited, Welwyn Garden City, Hertfordshire, UK |
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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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Keywords: | GPCR Class B druggability CRF1 receptor GPCR molecular signature HHM smoothened receptor glucagon receptor |
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