Allosteric binding sites on cell-surface receptors: novel targets for drug discovery.
Cell-surface receptors are the targets for more than 60% of current drugs. Traditionally, optimizing the interaction of lead molecules with the binding site for the endogenous agonist (orthosteric site) has been viewed as the best means of achieving selectivity of action. However, recent developments have highlighted the fact that drugs can interact with binding sites on the receptor molecule that are distinct from the orthosteric site, known as allosteric sites. Allosteric modulators could offer several advantages over orthosteric ligands, including greater selectivity and saturability of their effect.
Department of Pharmacology, University of Melbourne, Grattan Street, Parkville, Victoria 3010, Australia. arthurc1@unimelb.edu.au
Arthur
A
Christopoulos
D000495:Allosteric Site; D000818:Animals; D006801:Humans; D007700:Kinetics; D004364:Pharmaceutical Preparations / Q000737:chemistry; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000502:physiology; D013329:Structure-Activity Relationship
D004364:Pharmaceutical Preparations; D011956:Receptors, Cell Surface