Design of compound libraries for fragment screening

被引：58

作者：

Blomberg, Niklas ^{[2
]}

Cosgrove, David A. ^{[1
]}

Kenny, Peter W. ^{[1
]}

Kolmodin, Karin ^{[3
]}

机构：

[1] AstraZeneca R&D Alderley Pk, Macclesfield SK10 4TG, Cheshire, England

[2] AstraZeneca R&D, S-43183 Molndal, Sweden

[3] AstraZeneca R&D Sodertalje, S-15185 Sodertalje, Sweden

来源：

JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN | 2009年 / 23卷 / 08期

关键词：

Fragment based; Fragment based drug discovery; Fragment based lead generation; Fragment screening; FBDD; FBLG; NMR screening; Screening library; Library design; Molecular complexity; Molecular similarity; Neighborhood; Fingerprint; Foyfi; Flush; Bigpicker; Filter; Leatherface; SMARTS; Solubility; LEAD GENERATION; BETA-SECRETASE; BINDING-SITES; HOT-SPOTS; DISCOVERY; NMR; INHIBITORS; VALIDATION; SIMILARITY; STRATEGY;

D O I：

10.1007/s10822-009-9264-5

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：

Approaches to the design of libraries for fragment screening are illustrated with reference to a 20 k generic fragment screening library and a 1.2 k generic NMR screening library. Tools and methods for library design that have been developed within AstraZeneca are described, including Foyfi fingerprints and the Flush program for neighborhood characterization. It will be shown how Flush and the BigPicker, which selects maximally diverse sets of compounds, are used to apply the Core and Layer method for library design. Approaches to partitioning libraries into cocktails are also described.

引用

页码：513 / 525

页数：13

共 52 条

[31] Fragment-based lead discovery using X-ray crystallography [J].

Hartshorn, MJ ;

Murray, CW ;

Cleasby, A ;

Frederickson, M ;

Tickle, IJ ;

Jhoti, H .

JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (02) :403-413

[32] 5-substituted-1H-tetrazoles as carboxylic acid isosteres:: Medicinal chemistry and synthetic methods [J].

Herr, RJ .

BIOORGANIC & MEDICINAL CHEMISTRY, 2002, 10 (11) :3379-3393

[33] Fragment-based activity space: smaller is better [J].

Hesterkamp, Thomas ;

Whittaker, Mark .

CURRENT OPINION IN CHEMICAL BIOLOGY, 2008, 12 (03) :260-268

[34] Novel prostaglandin D synthase inhibitors generated by fragment-based drug design [J].

Hohwy, Morten ;

Spadola, Loredana ;

Lundquist, Britta ;

Hawtin, Paul ;

Dahmen, Jan ;

Groth-Clausen, Ib ;

Nilsson, Ewa ;

Persdotter, Sofia ;

Von Wachenfeldt, Karin ;

Folmer, Rutger H. A. ;

Edman, Karl .

JOURNAL OF MEDICINAL CHEMISTRY, 2008, 51 (07) :2178-2186

[35]

HSIEH P, HASH CODES

[36] ON THE ATTRIBUTION AND ADDITIVITY OF BINDING-ENERGIES [J].

JENCKS, WP .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1981, 78 (07) :4046-4050

[37] Fragment-based screening using X-ray crystallography and NMR spectroscopy [J].

Jhoti, Harren ;

Cleasby, Anne ;

Verdonk, Marcel ;

Williams, Glyn .

CURRENT OPINION IN CHEMICAL BIOLOGY, 2007, 11 (05) :485-493

[38]

Kenny PW, 2005, METH PRIN MED CHEM, V22, P271, DOI 10.1002/3527603743.ch11

[39] Multifingerprint based similarity searches for targeted class compound selection [J].

Kogej, Thierry ;

Engkvist, Ola ;

Blomberg, Niklas ;

Muresan, Sorel .

JOURNAL OF CHEMICAL INFORMATION AND MODELING, 2006, 46 (03) :1201-1213

[40] Statistical tools for virtual screening [J].

Krumrine, JR ;

Maynard, AT ;

Lerman, CL .

JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (23) :7477-7481

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