G-protein-coupled receptor allosterism: the promise and the problem(s). (26th October 2004)

• Record Type: Journal Article
• Authors: Christopoulos, A.; May, L.T.; Avlani, V.A.; Sexton, P.M.
• Is Part Of: Biochemical Society transactions. Volume 32:Number 5(2004)
• Page Start: 873
• Page End: 877
• Publication Date: 2004-10-26
• Subjects: allosteric interaction -- drug discovery -- G-protein-coupled receptor -- kinetics -- ternary complex model; Biochemistry -- Congresses; 572
• DOI: 10.1042/BST0320873
• Languages: English
• ISSNs: 0300-5127

Abstract

Abstract : Allosteric modulators of G-protein-coupled receptors interact with binding sites that are topographically distinct from the orthosteric site recognized by the receptor's endogenous agonist. Allosteric ligands offer a number of advantages over orthosteric drugs, including the potential for greater receptor subtype selectivity and a more 'physiological' regulation of receptor activity. However, the manifestations of allosterism at G-protein-coupled receptors are quite varied, and significant challenges remain for the optimization of screening methods to ensure the routine detection and validation of allosteric ligands.