Toxicogenomics in drug discovery and development:: mechanistic analysis of compound/class-dependent effects usign the DrugMatrix® database

被引:92
作者
Ganter, Brigitte
Snyder, Ronald D.
Halbert, Donald N.
Lee, May D.
机构
[1] Iconix Biosci, Mountain View, CA USA
[2] Schering Plough Res Inst, Summit, NJ USA
关键词
drug discovery and development; inducible nitric oxide synthase; mechanism of action; mechanism of toxicity; microarray expression data; CYP gene expression; phosphodiesterase inhibitors; RXR protein function; toxicogenomics;
D O I
10.2217/14622416.7.7.1025
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
A range of genomics technologies are increasingly becoming integrated with existing scientific disciplines to broaden and strengthen existing capabilities and open new avenues of research in drug discovery and development. Examples of these new research fields are proteomics, pharmacogenomics, metabolomics and toxicogenomics. Here we review the application of toxicogenomics to improve the evaluation of drug safety, mechanism of action and toxicity in the drug discovery and development process.
引用
收藏
页码:1025 / 1044
页数:20
相关论文
共 112 条
  • [61] Phenotypic anchoring of gene expression changes during estrogen-induced uterine growth
    Moggs, JG
    Tinwell, H
    Spurway, T
    Chang, HS
    Pate, I
    Lim, FL
    Moore, DJ
    Soames, A
    Stuckey, R
    Currie, R
    Zhu, T
    Kimber, I
    Ashby, J
    Orphanides, G
    [J]. ENVIRONMENTAL HEALTH PERSPECTIVES, 2004, 112 (16) : 1589 - 1606
  • [62] Moos PJ, 2002, CLIN CANCER RES, V8, P3118
  • [63] Regulation of cytochromes P450 during inflammation and infection
    Morgan, ET
    [J]. DRUG METABOLISM REVIEWS, 1997, 29 (04) : 1129 - 1188
  • [64] Morgan ET, 2001, DRUG METAB DISPOS, V29, P207
  • [65] Classification of a large microarray data set: Algorithm comparison and analysis of drug signatures
    Natsoulis, G
    El Ghaoui, L
    Lanckriet, GRG
    Tolley, AM
    Leroy, F
    Dunlea, S
    Eynon, BP
    Pearson, CI
    Tugendreich, S
    Jarnagin, K
    [J]. GENOME RESEARCH, 2005, 15 (05) : 724 - 736
  • [66] The utility of DNA microarrays for characterizing genotoxicity
    Newton, RK
    Aardema, M
    Aubrecht, J
    [J]. ENVIRONMENTAL HEALTH PERSPECTIVES, 2004, 112 (04) : 420 - 422
  • [67] Inhibition of AP-1 DNA binding by nitric oxide involving conserved cysteine residues in Jun and Fos
    Nikitovic, D
    Holmgren, A
    Spyrou, G
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1998, 242 (01) : 109 - 112
  • [68] Nuwaysir EF, 1999, MOL CARCINOGEN, V24, P153, DOI 10.1002/(SICI)1098-2744(199903)24:3<153::AID-MC1>3.0.CO
  • [69] 2-P
  • [70] Human and animal hepatocytes in vitro with extrapolation in vivo
    O'Brien, PJ
    Chan, K
    Silber, PM
    [J]. CHEMICO-BIOLOGICAL INTERACTIONS, 2004, 150 (01) : 97 - 114