The impact of genomics-based technologies on drug safety evaluation

被引:34
作者
Waring, JF [1 ]
Ulrich, RG [1 ]
机构
[1] Abbott Labs, Strateg & Exploratory Sci, Abbott Pk, IL 60064 USA
关键词
molecular toxicology; microarrays; high throughput; real-time PCR; drug screening;
D O I
10.1146/annurev.pharmtox.40.1.335
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Determining the potential toxicity of compounds early in the drug discovery process can be extremely beneficial in terms of both time and money conservation. Because of the speed of modern chemical synthesis and screening, to accurately evaluate the large number of compounds being produced, toxicology assays must have both high-fidelity and high-throughput capabilities. In addition, assays must be performed using Limited amounts of compound. In the past decade, several new and innovative techniques have been developed that not only allow for high-throughput screening but can also provide detailed information concerning the molecular mechanisms behind toxic effects. Techniques such as hybridization microarrays, real-time polymerase chain reaction, and large-scale sequencing are some of the methods that have been or are starting to be used routinely in pharmaceutical companies. This review examines the contributions of these and related techniques toward toxicity evaluation of potential drug candidates and their future role in the discovery of new therapeutics.
引用
收藏
页码:335 / 352
页数:18
相关论文
共 54 条
[1]   High-throughput gene expression analysis using SAGE [J].
Bertelsen, AH ;
Velculescu, VE .
DRUG DISCOVERY TODAY, 1998, 3 (04) :152-159
[2]   Options available - from start to finish - for obtaining expression data by microarray [J].
Bowtell, DDL .
NATURE GENETICS, 1999, 21 (Suppl 1) :25-32
[3]   Risk assessment [J].
Brecher, RW .
TOXICOLOGIC PATHOLOGY, 1997, 25 (01) :23-26
[4]  
CHEN I, 1999, TOXICOL SCI, V48, P1007
[5]   SACCHAROMYCES CEREVISIAE 3-METHYLADENINE DNA GLYCOSYLASE HAS HOMOLOGY TO THE ALKA GLYCOSYLASE OF ESCHERICHIA-COLI AND IS INDUCED IN RESPONSE TO DNA ALKYLATION DAMAGE [J].
CHEN, J ;
DERFLER, B ;
SAMSON, L .
EMBO JOURNAL, 1990, 9 (13) :4569-4575
[6]   Making and reading microarrays [J].
Cheung, VG ;
Morley, M ;
Aguilar, F ;
Massimi, A ;
Kucherlapati, R ;
Childs, G .
NATURE GENETICS, 1999, 21 (Suppl 1) :15-19
[7]   CCL4-INDUCED INCREASE OF HEPATOCYTE FREE ARACHIDONATE LEVEL - PATHOGENESIS AND CONTRIBUTION TO CELL-DEATH [J].
CHIARPOTTO, E ;
BIASI, F ;
COMOGLIO, A ;
LEONARDUZZI, G ;
POLI, G ;
DIANZANI, MU .
CHEMICO-BIOLOGICAL INTERACTIONS, 1990, 74 (1-2) :195-206
[8]   Identification of genes differentially regulated by interferon α, β, or γ using oligonucleotide arrays [J].
Der, SD ;
Zhou, AM ;
Williams, BRG ;
Silverman, RH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (26) :15623-15628
[9]   Suppression subtractive hybridization: A method for generating differentially regulated or tissue-specific cDNA probes and libraries [J].
Diatchenko, L ;
Lau, YFC ;
Campbell, AP ;
Chenchik, A ;
Moqadam, F ;
Huang, B ;
Lukyanov, S ;
Lukyanov, K ;
Gurskaya, N ;
Sverdlov, ED ;
Siebert, PD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (12) :6025-6030
[10]   Analysis of gene expression in lung and thymus of TCDD treated C57BL6 mice using differential display RT-PCR [J].
Donat, S ;
Abel, J .
CHEMOSPHERE, 1998, 37 (9-12) :1867-1872