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Neurochemical Research

, Volume 28, Issue 2, pp 367–371 | Cite as

Target Discovery and Validation in the Post-Genomic Era

  • Steven P. Butcher
Article

Abstract

The recent publication of the human genome sequence provides an opportunity both to combat diseases that are presently considered as pharmaceutically intractable and also to improve current therapies for many common human diseases. The identification of every human gene by ongoing bioinformatic efforts has the potential, when combined with functional genomic approaches, to pinpoint the molecular basis of every human disease, and to discover appropriate intervention points. This exciting prospect is directly relevant to the successful development of effective therapeutics because the past record of drug discovery suggests that 30%–40% of experimental drugs fail because an inappropriate biological target was pursued. The major impact of genomic information may therefore be to reduce this biological failure rate by earlier definition of drug targets related to disease susceptibility or progression. This paper briefly reviews some of the approaches that can be used to identify biologically relevant drug targets.

Genomics target validation drug target 

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REFERENCES

  1. 1.
    Ventner J. C., Adams, M. D., Myers, E. W., et al. 2001. The sequence of the human genome. Science 291:1304–1351.PubMedGoogle Scholar
  2. 2.
    International Human Genome Sequence Consortium. 2001. Initial sequencing and analysis of the human genome. Nature 409:860–921.Google Scholar
  3. 3.
    International SNP Map Working Group. 2001. A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms. Nature 409:928–933.Google Scholar
  4. 4.
    Kazemi-Esfarjani, P. and Benzer, S. 2000. Genetic suppression of polyglutamine toxicity in Drosophila. Science 287:1837–1840.PubMedGoogle Scholar
  5. 5.
    Nass, R., Miller, D. M., and Blakely, R. D. 2002. Neurotoxin-induced degeneration of dopamine neurons in Caenorhabditis elegans. Proc. Natl. Acad. Sci. 99:3264–3269.PubMedGoogle Scholar
  6. 6.
    Nolan, P. M., Peters, J., Rogers, D. et al. 2000. A systematic, genome-wide, phenotype driven mutagenesis programme for gene function studies in the mouse. Nat. Genet. 25:440–443.PubMedGoogle Scholar
  7. 7.
    Hrabe de Angelis, M., Flawinkel, H., Fuchs, H., et al. 2000. Genome-wide, large scale production of mutant mice by ENU mutagenesis. Nat. Genet. 25:444–447.PubMedGoogle Scholar
  8. 8.
    Lewandowski, M. 2001. Conditional control of gene expression in the mouse. Nat. Rev. Genet. 2:743–755.PubMedGoogle Scholar
  9. 9.
    Wahlestedt, C., Salmi, P., Good, L., et al. 2000. Potent and non-toxic antisense oligonucleotides containing locked nucleic acids. Proc. Natl. Acad. Sci. 97:5633–5638.PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 2003

Authors and Affiliations

  • Steven P. Butcher
    • 1
  1. 1.Synaptica Research Ltd.DidcotUnited Kingdom

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