Drug target validation and identification of secondary drug target effects using DNA microarrays View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1998-11

AUTHORS

M J Marton, J L DeRisi, H A Bennett, V R Iyer, M R Meyer, C J Roberts, R Stoughton, J Burchard, D Slade, H Dai, D E Bassett, L H Hartwell, P O Brown, S H Friend

ABSTRACT

We describe here a method for drug target validation and identification of secondary drug target effects based on genome-wide gene expression patterns. The method is demonstrated by several experiments, including treatment of yeast mutant strains defective in calcineurin, immunophilins or other genes with the immunosuppressants cyclosporin A or FK506. Presence or absence of the characteristic drug 'signature' pattern of altered gene expression in drug-treated cells with a mutation in the gene encoding a putative target established whether that target was required to generate the drug signature. Drug dependent effects were seen in 'targetless' cells, showing that FK506 affects additional pathways independent of calcineurin and the immunophilins. The described method permits the direct confirmation of drug targets and recognition of drug-dependent changes in gene expression that are modulated through pathways distinct from the drug's intended target. Such a method may prove useful in improving the efficiency of drug development programs. More... »

PAGES

1293-1301

References to SciGraph publications

Journal

TITLE

Nature Medicine

ISSUE

11

VOLUME

4

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/3282

    DOI

    http://dx.doi.org/10.1038/3282

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1011136384

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/9809554


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