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
相关论文
共 69 条
[1]   The genome sequence of Drosophila melanogaster [J].
Adams, MD ;
Celniker, SE ;
Holt, RA ;
Evans, CA ;
Gocayne, JD ;
Amanatides, PG ;
Scherer, SE ;
Li, PW ;
Hoskins, RA ;
Galle, RF ;
George, RA ;
Lewis, SE ;
Richards, S ;
Ashburner, M ;
Henderson, SN ;
Sutton, GG ;
Wortman, JR ;
Yandell, MD ;
Zhang, Q ;
Chen, LX ;
Brandon, RC ;
Rogers, YHC ;
Blazej, RG ;
Champe, M ;
Pfeiffer, BD ;
Wan, KH ;
Doyle, C ;
Baxter, EG ;
Helt, G ;
Nelson, CR ;
Miklos, GLG ;
Abril, JF ;
Agbayani, A ;
An, HJ ;
Andrews-Pfannkoch, C ;
Baldwin, D ;
Ballew, RM ;
Basu, A ;
Baxendale, J ;
Bayraktaroglu, L ;
Beasley, EM ;
Beeson, KY ;
Benos, PV ;
Berman, BP ;
Bhandari, D ;
Bolshakov, S ;
Borkova, D ;
Botchan, MR ;
Bouck, J ;
Brokstein, P .
SCIENCE, 2000, 287 (5461) :2185-2195
[2]   Zebrafish as a cancer model system [J].
Amatruda, JF ;
Shepard, JL ;
Stern, HM ;
Zon, LI .
CANCER CELL, 2002, 1 (03) :229-231
[3]   Identification of 315 genes essential for early zebrafish development [J].
Amsterdam, A ;
Nissen, RM ;
Sun, ZX ;
Swindell, EC ;
Farrington, S ;
Hopkins, N .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (35) :12792-12797
[4]   Genome-wide RNAi analysis of Caenorhabditis elegans fat regulatory genes [J].
Ashrafi, K ;
Chang, FY ;
Watts, JL ;
Fraser, AG ;
Kamath, RS ;
Ahringer, J ;
Ruvkun, G .
NATURE, 2003, 421 (6920) :268-272
[5]   Identification of modulators of TRAIL-induced apoptosis via RNAi-based phenotypic screening [J].
Aza-Blanc, P ;
Cooper, CL ;
Wagner, K ;
Batalov, S ;
Deveraux, QL ;
Cooke, MP .
MOLECULAR CELL, 2003, 12 (03) :627-637
[6]   ENU mutagenesis: Analyzing gene function in mice [J].
Balling, R .
ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS, 2001, 2 :463-492
[7]   A large-scale RNAi screen in human cells identifies new components of the p53 pathway [J].
Berns, K ;
Hijmans, EM ;
Mullenders, J ;
Brummelkamp, TR ;
Velds, A ;
Heimerikx, M ;
Kerkhoven, RM ;
Madiredjo, M ;
Nijkamp, W ;
Weigelt, B ;
Agami, R ;
Ge, W ;
Cavet, G ;
Linsley, PS ;
Beijersbergen, RL ;
Bernards, R .
NATURE, 2004, 428 (6981) :431-437
[8]  
BRENNER S, 1974, GENETICS, V77, P71
[9]   Induction of an interferon response by RNAi vectors in mammalian cells [J].
Bridge, AJ ;
Pebernard, S ;
Ducraux, A ;
Nicoulaz, AL ;
Iggo, R .
NATURE GENETICS, 2003, 34 (03) :263-264
[10]  
*CAEN EL SEQ CONS, 1998, SCIENCE, V252, P2012