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ID: ALA2057094

Journal: Bioorg Med Chem Lett

Title: Inhibition of VEGF transcription through blockade of the hypoxia inducible factor-1α-p300 interaction by a small molecule.

Authors: Kwon HS, Kim DR, Yang EG, Park YK, Ahn HC, Min SJ, Ahn DR.

Abstract: Vascular endothelial growth factor (VEGF) plays a pro-angiogenic role in tumor progression. Stabilization of a key regulator termed the hypoxia inducible factor (HIF)-1α under oxygen deficient environment around tumor is known to elicit expression of VEGF through binding to p300. Thus, inhibition of the HIF-1α-p300 interaction would lead to down-regulation of VEGF expression, thereby providing potential cancer therapeutics. Here, we have screened a chemical library against the interaction of the HIF-1α-derived peptide with p300 employing a fluorescence polarization-based assay. We have identified a compound as the most prominent inhibitor against the protein-protein interaction. Further, we have observed suppression of the mRNA level of VEGF upon treatment of HeLa cells with the compound, demonstrating its inhibitory effect at the cellular level.

CiteXplore: 22789427

DOI: 10.1016/j.bmcl.2012.06.054