Virtual screening in lead discovery: A viewpoint

被引：85

作者：

Oprea, TL ^{[1
]}

机构：

[1] AstraZeneca R&D, EST Lead Informat, S-43183 Molndal, Sweden

来源：

MOLECULES | 2002年 / 7卷 / 01期

关键词：

ADME filters; combinatorial library design; drug discovery;

D O I：

10.3390/70100051

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Virtual screening (VS) methods have emerged as an adaptive response to massive throughput synthesis and screening technologies. Based on the structure-permeability paradigm, the Lipinski rule of five has become a standard property filtering protocol for VS. Three possible VS scenarios with respect to optimising binding affinity and pharmacokinetic properties are discussed. The parsimony principle for selecting candidate leads for further optimisation is advocated.

引用

页码：51 / 62

页数：12

共 48 条

[1] Consensus scoring: A method for obtaining improved hit rates from docking databases of three-dimensional structures into proteins [J].

Charifson, PS ;

Corkery, JJ ;

Murcko, MA ;

Walters, WP .

JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (25) :5100-5109

[2] Rapid calculation of polar molecular surface area and its application to the prediction of transport phenomena. 2. Prediction of blood-brain barrier penetration [J].

Clark, DE .

JOURNAL OF PHARMACEUTICAL SCIENCES, 1999, 88 (08) :815-821

[3] Rapid calculation of polar molecular surface area and its application to the prediction of transport phenomena. 1. Prediction of intestinal absorption [J].

Clark, DE .

JOURNAL OF PHARMACEUTICAL SCIENCES, 1999, 88 (08) :807-814

[4] Predicting blood-brain barrier permeation from three-dimensional molecular structure [J].

Crivori, P ;

Cruciani, G ;

Carrupt, PA ;

Testa, B .

JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (11) :2204-2216

[5] Molecular fields in quantitative structure-permeation relationships: the VolSurf approach [J].

Cruciani, C ;

Crivori, P ;

Carrupt, PA ;

Testa, B .

JOURNAL OF MOLECULAR STRUCTURE-THEOCHEM, 2000, 503 (1-2) :17-30

[6]

Darvas F, 1999, CHIM OGGI, V17, P10

[7]

Davis AM, 1999, ANGEW CHEM INT EDIT, V38, P737, DOI 10.1002/(SICI)1521-3773(19990315)38:6<736::AID-ANIE736>3.0.CO

[8]

2-R

[9] Drug discovery: A historical perspective [J].

Drews, J .

SCIENCE, 2000, 287 (5460) :1960-1964

[10] Innovation deficit revisited: reflections on the productivity of pharmaceutical R&D [J].

Drews, J .

DRUG DISCOVERY TODAY, 1998, 3 (11) :491-494

← 1 2 3 4 5 →