Dataset Information


Transcription profiling of human cell lines under bioreductive prodrug PR-104A

ABSTRACT: A variety of human cell lines, were grown, RNA was extracted, and gene expression quantified using Affymetrix hgu133plus2 arrays. Expression of genes was compared to the rate of metabolism of the bioreductive prodrug PR-104A, and genes with expression shown to be statistically significantly correlated to pro-drug metabolic rate were chosen for further investigation.

INSTRUMENT(S): 418 [Affymetrix]

ORGANISM(S): Homo sapiens  

SUBMITTER: Rob Pollock  

PROVIDER: E-TABM-767 | ArrayExpress | 2009-08-25


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PR-104, currently in phase II clinical trials, is a phosphate ester pre-prodrug which is converted in vivo to its cognate alcohol, PR-104A, a prodrug designed to exploit tumor hypoxia. Bioactivation occurs via one-electron reduction to DNA crosslinking metabolites in the absence of oxygen. However, certain tumor cell lines activate PR-104A in the presence of oxygen, suggesting the existence of an aerobic nitroreductase. Microarray analysis identified a cluster of five aldo-keto reductase (AKR) f  ...[more]

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