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

Autor: Bortolato A; Heptares Therapeutics Limited, Welwyn Garden City, Hertfordshire, UK., Doré AS, Hollenstein K, Tehan BG, Mason JS, Marshall FH
Jazyk: angličtina
Zdroj: British journal of pharmacology [Br J Pharmacol] 2014 Jul; Vol. 171 (13), pp. 3132-45.
DOI: 10.1111/bph.12689
Abstrakt: 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.
(© 2014 The British Pharmacological Society.)
Databáze: MEDLINE
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