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- W2000975094 abstract "Vascular endothelial growth factor (VEGF) and its receptors have been implicated as key factors in tumor angiogenesis that are up-regulated by hypoxia. We evaluated the effects of DNA-binding small molecules on hypoxia-inducible transcription of VEGF . A synthetic pyrrole-imidazole polyamide designed to bind the hypoxia response element (HRE) was found to disrupt hypoxia-inducible factor (HIF) binding to HRE. In cultured HeLa cells, this resulted in a reduction of VEGF mRNA and secreted protein levels. The observed effects were polyamide-specific and dose-dependent. Analysis of genome-wide effects of the HRE-specific polyamide revealed that a number of hypoxia-inducible genes were down-regulated. Pathway-based regulation of hypoxia-inducible gene expression with DNA-binding small molecules may represent a new approach for targeting angiogenesis." @default.
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- W2000975094 date "2004-11-19" @default.
- W2000975094 modified "2023-10-07" @default.
- W2000975094 title "Inhibition of vascular endothelial growth factor with a sequence-specific hypoxia response element antagonist" @default.
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- W2000975094 doi "https://doi.org/10.1073/pnas.0407617101" @default.
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