Allosteric modulators of GPCRs: a novel approach for the treatment of CNS disorders

被引：867

作者：

Conn, P. Jeffrey ^{[1
]}

Christopoulos, Arthur ^{[2
,3
]}

Lindsley, Craig W. ^{[1
,4
]}

机构：

[1] Vanderbilt Univ Sch Med, Vanderbilt Program Drug Discovery, Dept Pharmacol, Nashville, TN 37232 USA

[2] Monash Univ, Drug Discovery Biol Lab, Monash Inst Pharmaceut Sci, Melbourne, Vic 3004, Australia

[3] Monash Univ, Dept Pharmacol, Melbourne, Vic 3004, Australia

[4] Vanderbilt Univ, Dept Chem, Nashville, TN 37232 USA

来源：

NATURE REVIEWS DRUG DISCOVERY | 2009年 / 8卷 / 01期

关键词：

METABOTROPIC GLUTAMATE RECEPTORS; PROTEIN-COUPLED RECEPTORS; MUSCARINIC ACETYLCHOLINE-RECEPTORS; METHYL-D-ASPARTATE; CALCIUM SENSING RECEPTOR; SMALL-MOLECULE INHIBITOR; SUBTYPE SELECTIVITY; BINDING-SITE; 2-METHYL-6-(PHENYLETHYNYL)-PYRIDINE MPEP; NONCOMPETITIVE ANTAGONISTS;

D O I：

10.1038/nrd2760

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 [微生物学]; 090105 [作物生产系统与生态工程];

摘要：

Despite G-protein-coupled receptors (GPCRs) being among the most fruitful targets for marketed drugs, intense discovery efforts for several GPCR subtypes have failed to deliver selective drug candidates. Historically, drug discovery programmes for GPCR ligands have been dominated by efforts to develop agonists and antagonists that act at orthosteric sites for endogenous ligands. However, in recent years, there have been tremendous advances in the discovery of novel ligands for GPCRs that act at allosteric sites to regulate receptor function. These compounds provide high selectivity, novel modes of efficacy and may lead to novel therapeutic agents for the treatment of multiple psychiatric and neurological human disorders.

引用

页码：41 / 54

页数：14

共 135 条

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Activation of NMDA receptors reverses desensitization of mGluR5 in native and recombinant systems [J].