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

Hyuk Sung Kwon, Da Rae Kim, Eun Gyeong Yang, Yong Keun Park, Hee Chul Ahn, Sun Joon Min, Dae Ro Ahn

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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.

Original languageEnglish
Pages (from-to)5249-5252
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume22
Issue number16
DOIs
StatePublished - 15 Aug 2012

Keywords

  • Fluorescence polarization
  • HIF-1α-p300 interaction
  • Inhibitor
  • Protein-protein interaction
  • VEGF

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