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Br J Pharmacol. 2014 Jul;171(13):3132-45. doi: 10.1111/bph.12689.

Structure of Class B GPCRs: new horizons for drug discovery.

Author information

1
Heptares 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.

KEYWORDS:

CRF1 receptor; Class B; GPCR; GPCR molecular signature; HHM; druggability; glucagon receptor; smoothened receptor

PMID:
24628305
PMCID:
PMC4080969
DOI:
10.1111/bph.12689
[Indexed for MEDLINE]
Free PMC Article

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