Allosteric binding sites on cell-surface receptors: Novel targets for drug discovery

被引：535
作者：
Christopoulos, A [1 ]
机构：
[1] Univ Melbourne, Dept Pharmacol, Parkville, Vic 3010, Australia
来源：
NATURE REVIEWS DRUG DISCOVERY | 2002年 / 1卷 / 03期
基金：
英国医学研究理事会;
关键词：
D O I：
10.1038/nrd746
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 ; 0836 ; 090102 ; 100705 ;
摘要：
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.
引用
收藏
页码：198 / 210
页数：13
相关论文
共 130 条
[71]   Two-point kinetic experiments to quantify allosteric effects on radioligand dissociation [J].
Kostenis, E ;
Mohr, K .
TRENDS IN PHARMACOLOGICAL SCIENCES, 1996, 17 (08) :280-283
[72]  
Kostenis E, 1996, TRENDS PHARMACOL SCI, V17, P443
[73]   Differential effects of the allosteric enhancer (2-amino-4,5-dimethyl-trienyl)[3-(trifluoromethyl) phenyl]methanone (PD81,723) on agonist and antagonist binding and function at the human wild-type and a mutant (T277A) adenosine A1 receptor [J].
Kourounakis, A ;
Visser, C ;
de Groote, M ;
IJzerman, AP .
BIOCHEMICAL PHARMACOLOGY, 2001, 61 (02) :137-144
[74]   Ivermectin:: A positive allosteric effector of the α7 neuronal nicotinic acetylcholine receptor [J].
Krause, RM ;
Buisson, B ;
Bertrand, S ;
Corringer, PJ ;
Galzi, JL ;
Changeux, JP ;
Bertrand, D .
MOLECULAR PHARMACOLOGY, 1998, 53 (02) :283-294
[75]   The pharmacology of amino-acid responses in septal neurons [J].
Kumamoto, E .
PROGRESS IN NEUROBIOLOGY, 1997, 52 (03) :197-259
[76]  
LANGLEY JN, 1906, J PHYSIOL-LONDON, V34, P170
[77]   Interactions of agonists with an allosteric antagonist at muscarinic acetylcholine M(2) receptors [J].
Lanzafame, A ;
Christopoulos, A ;
Mitchelson, F .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1996, 316 (01) :27-32
[78]  
LAZARENO S, 1995, MOL PHARMACOL, V48, P362
[79]   Subtype-selective positive cooperative interactions between brucine analogues and acetylcholine at muscarinic receptors: Radioligand binding studies [J].
Lazareno, S ;
Gharagozloo, P ;
Kuonen, D ;
Popham, A ;
Birdsall, NJM .
MOLECULAR PHARMACOLOGY, 1998, 53 (03) :573-589
[80]  
LAZARENO S, 1998, DRUGS PHARM SCI, V89, P49
3456789101112