Phenotype-first screening for the identification of novel drug targets

被引:20
作者
Austen, M [1 ]
Dohrmann, C [1 ]
机构
[1] DeveloGen AG, D-37079 Gottingen, Germany
关键词
D O I
10.1016/S1359-6446(05)03368-4
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Modem drug discovery is predominantly a target-driven process, where success is intricately linked to the selection of an appropriate molecular target. Ideally, there is conclusive functional evidence that a selected target is disease-relevant and, furthermore, suitable for drug development. Phenotype-first screening is a highly attractive approach for target identification because it offers the unique possibility to analyse entire genomes in an unbiased fashion for disease-related phenotypes. Various studies have demonstrated that phenotype-first screening can be successfully applied to the identification of drug targets, thus establishing this approach as a valuable tool for future target discovery efforts.
引用
收藏
页码:275 / 282
页数:8
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共 69 条
[41]   Mouse mutants from chemically mutagenized embryonic stem cells [J].
Munroe, RJ ;
Bergstrom, RA ;
Zheng, QY ;
Libby, B ;
Smith, R ;
John, SWM ;
Schimenti, KJ ;
Browning, VL ;
Schimenti, JC .
NATURE GENETICS, 2000, 24 (03) :318-321
[42]   Effective targeted gene 'knockdown' in zebrafish [J].
Nasevicius, A ;
Ekker, SC .
NATURE GENETICS, 2000, 26 (02) :216-220
[43]   A systematic, genome-wide, phenotype-driven mutagenesis programme for gene function studies in the mouse [J].
Nolan, PM ;
Peters, J ;
Strivens, M ;
Rogers, D ;
Hagan, J ;
Spurr, N ;
Gray, IC ;
Vizor, L ;
Brooker, D ;
Whitehill, E ;
Washbourne, R ;
Hough, T ;
Greenaway, S ;
Hewitt, M ;
Liu, XH ;
McCormack, S ;
Pickford, K ;
Selley, R ;
Wells, C ;
Tymowska-Lalanne, Z ;
Roby, P ;
Glenister, P ;
Thornton, C ;
Thaung, C ;
Stevenson, JA ;
Arkell, R ;
Mburu, P ;
Hardisty, R ;
Kiernan, A ;
Erven, H ;
Steel, KP ;
Voegeling, S ;
Guenet, JL ;
Nickols, C ;
Sadri, R ;
Naase, M ;
Isaacs, A ;
Davies, K ;
Browne, M ;
Fisher, EMC ;
Martin, J ;
Rastan, S ;
Brown, SDM ;
Hunter, J .
NATURE GENETICS, 2000, 25 (04) :440-443
[44]   Modeling human hematopoietic and cardiovascular diseases in zebrafish [J].
North, TE ;
Zon, LI .
DEVELOPMENTAL DYNAMICS, 2003, 228 (03) :568-583
[45]   A genetic screen in Drosophila for metastatic behavior [J].
Pagliarini, RA ;
Xu, T .
SCIENCE, 2003, 302 (5648) :1227-1231
[46]   PI3Kγ modulates the cardiac response to chronic pressure overload by distinct kinase-dependent and -independent effects [J].
Patrucco, E ;
Notte, A ;
Barberis, L ;
Selvetella, G ;
Maffei, A ;
Brancaccio, M ;
Marengo, S ;
Russo, G ;
Azzolino, O ;
Rybalkin, SD ;
Silengo, L ;
Altruda, F ;
Wetzker, R ;
Wymann, MP ;
Lembo, G ;
Hirsch, E .
CELL, 2004, 118 (03) :375-387
[47]   The art and design of genetic screens: Zebrafish [J].
Patton, EE ;
Zon, LI .
NATURE REVIEWS GENETICS, 2001, 2 (12) :956-966
[48]   Chemical suppression of a genetic mutation in a zebrafish model of aortic coarctation [J].
Peterson, RT ;
Shaw, SY ;
Peterson, TA ;
Milan, DJ ;
Zhong, TP ;
Schreiber, SL ;
MacRae, CA ;
Fishman, MC .
NATURE BIOTECHNOLOGY, 2004, 22 (05) :595-599
[49]   Small molecule developmental screens reveal the logic and timing of vertebrate development [J].
Peterson, RT ;
Link, BA ;
Dowling, JE ;
Schreiber, SL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (24) :12965-12969
[50]   Drosophila in cancer research -: an expanding role [J].
Potter, CJ ;
Turenchalk, GS ;
Xu, T .
TRENDS IN GENETICS, 2000, 16 (01) :33-39