Tools for target identification and validation

被引:62
作者
Wang, SL [1 ]
Sim, TB [1 ]
Chang, YT [1 ]
机构
[1] NYU, Dept Chem, New York, NY 10003 USA
关键词
D O I
10.1016/j.cbpa.2004.06.001
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
Reliable technologies for addressing target identification and validation are the foundation of successful drug development. Microarrays have been well utilized in genomics/proteomics approaches for gene/protein expression profiling and tissue/ cell-scale target validation. Besides being used as an essential step in analyzing high-throughput experiments such as those involving microarrays, bioinformatics can also contribute to the processes of target identification and validation by providing functional information about target candidates and positioning information to biological networks. Antisense technologies (including RNA interference technology, which is recently very 'hot') enable sequence-based gene knockdown at the RNA level. Zinc finger proteins are a DNA transcription-targeting version of knockdown. Chemical genomics and proteomics are emerging tools for generating phenotype changes, thus leading to target and hit identifications. NMR-based screening, as well as activity-based protein profiling, are trying to meet the requirement of high-throughput target identification.
引用
收藏
页码:371 / 377
页数:7
相关论文
共 44 条
[1]   RNAi and related mechanisms and their potential use for therapy [J].
Agami, R .
CURRENT OPINION IN CHEMICAL BIOLOGY, 2002, 6 (06) :829-834
[2]   Questioning the role of checkpoint kinase 2 in the p53 DNA damage response [J].
Ahn, JW ;
Urist, M ;
Prives, C .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (23) :20480-20489
[3]   Microarrays: the use of oligonucleotides and cDNA for the analysis of gene expression [J].
Barrett, JC ;
Kawasaki, ES .
DRUG DISCOVERY TODAY, 2003, 8 (03) :134-141
[4]   Standardization of protocols in cDNA microarray analysis [J].
Benes, V ;
Muckenthaler, M .
TRENDS IN BIOCHEMICAL SCIENCES, 2003, 28 (05) :244-249
[5]   Developing a strategy for activity-based detection of enzymes in a protein microarray [J].
Chen, GYJ ;
Uttamchandani, M ;
Zhu, Q ;
Wang, G ;
Yao, SQ .
CHEMBIOCHEM, 2003, 4 (04) :336-339
[6]   Small RNAs make big splash [J].
Couzin, J .
SCIENCE, 2002, 298 (5602) :2296-2297
[7]   Drug discovery: A historical perspective [J].
Drews, J .
SCIENCE, 2000, 287 (5460) :1960-1964
[8]   Extending the utility of gene profiling data by bridging microarray platforms [J].
Ferl, GZ ;
Timmerman, JM ;
Witte, ON .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (19) :10585-10587
[9]   In vivo we trust [J].
Simon Frantz .
Nature Reviews Drug Discovery, 2003, 2 (6) :501-501
[10]   Genomic profiling of drug sensitivities via induced haploinsufficiency [J].
Giaever, G ;
Shoemaker, DD ;
Jones, TW ;
Liang, H ;
Winzeler, EA ;
Astromoff, A ;
Davis, RW .
NATURE GENETICS, 1999, 21 (03) :278-283