TITLE

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

AUTHOR(S)

Marton, Matthew J.; DeRisi, Joseph L.; Bennett, Holly A.; Iyer, Vishwanath R.; Meyer, Michael R.; Roberts, Christopher J.; Stoughton, Roland; Burchard, Julja; Slade, David; Dai, Hongyue; Bassett, Douglas E.; Hartwell, Leland H.; Brown, Patrick O.; Friend, Stephen H.

PUB. DATE

November 1998

SOURCE

Nature Medicine;Nov98, Vol. 4 Issue 11, p1293

SOURCE TYPE

Academic Journal

DOC. TYPE

Article

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.

ACCESSION #

8818274

Tags: DRUG targeting;  GENE expression

 

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