Pharmaceutical profiling in drug discovery

被引:217
作者
Kerns, EH [1 ]
Di, L [1 ]
机构
[1] Wyeth Ayerst Res, Chem Sci, Discovery Analyt Chem, Princeton, NJ 08543 USA
关键词
D O I
10.1016/S1359-6446(03)02649-7
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Drug discovery research organizations are building capability for measuring an ensemble of crucial 'drug-like' properties. These structure-property relationship (SPR) data complement current SAR information. This pharmaceutical profiling strategy enables research teams to better plan and interpret discovery experiments, be alerted to potential 'show stoppers', improve property liabilities, and select the best candidates for advancement. High throughput property assays for physicochemical properties - solubility, permeability, lipophilicity, stability, and pK(a) - in vitro ADME - metabolism, transporters, protein binding and CYP inhibition - and in vivo PK/exposure provide a wealth of data for teams to make informed decisions.
引用
收藏
页码:316 / 323
页数:8
相关论文
共 69 条
[1]   Caco-2 monolayers in experimental and theoretical predictions of drug transport (Reprinted from Advanced Drug Delivery Reviews, vol 22, pg 67-84, 1996) [J].
Artursson, P ;
Palm, K ;
Luthman, K .
ADVANCED DRUG DELIVERY REVIEWS, 2001, 46 (1-3) :27-43
[2]  
ARTURSSON P, 2002, PAMPA 2002 C SAN FRA
[3]   Drug absorption in vitro model:: filter-immobilized artificial membranes 2.: Studies of the permeability properties of lactones in Piper methysticum Forst [J].
Avdeef, A ;
Strafford, M ;
Block, E ;
Balogh, MP ;
Chambliss, W ;
Khan, I .
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 2001, 14 (04) :271-280
[4]   High-throughput measurements of solubility profiles [J].
Avdeef, A .
PHARMACOKINETIC OPTIMIZATION IN DRUG RESEARCH: BIOLOGICAL, PHYSICOCHEMICAL, AND COMPUTATIONAL STRATEGIES, 2001, :305-325
[5]  
Bajpai M, 2000, Curr Opin Drug Discov Devel, V3, P63
[6]   Determination of dissociation constants of cytokinins by capillary zone electrophoresis [J].
Barták, P ;
Bednár, P ;
Stránsky, Z ;
Bocek, P ;
Vespalec, R .
JOURNAL OF CHROMATOGRAPHY A, 2000, 878 (02) :249-259
[7]   A high-throughput screening method for the determination of aqueous drug solubility using laser nephelometry in microtiter plates [J].
Bevan, CD ;
Lloyd, RS .
ANALYTICAL CHEMISTRY, 2000, 72 (08) :1781-1787
[8]  
Box K. J., 2000, HIGH THROUGHPUT SCRE, P67
[9]  
Caldwell G W, 2000, Curr Opin Drug Discov Devel, V3, P30
[10]  
Chu IH, 2000, RAPID COMMUN MASS SP, V14, P207, DOI 10.1002/(SICI)1097-0231(20000229)14:4<207::AID-RCM863>3.0.CO