Inhibition of VEGF transcription through blockade of the hypoxia inducible factor-1α–p300 interaction by a small molecule
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.
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References 19 · Cited by 21
- Authors
- Kwon, H. S., Kim, D.-R., Yang, E. G., Park, Y. K., Ahn, H.-C., Min, S.-J., & Ahn, D.-R.
- Affiliations
- Korea University (KR)
- Korea Institute of Science and Technology (KR)
- Dongguk University (KR)
- Corresponding author
- Ahn, Dae-Ro
- Venue
- Bioorganic & Medicinal Chemistry Letters
- Publisher
- Elsevier BV
- Published
- 2012-08
- Volume
- 22
- Issue
- 16
- Pages
- 5249-5252
- ISSN
- 0960-894X (ISSN-L)
- OpenAlex
- W2044539114
- Cited by
- 21
- References
- 19
- Citations by year
- 2026: 1 · 2022: 1 · 2021: 2 · 2019: 1 · 2018: 1 · 2016: 1 · 2015: 6 · 2014: 4 · 2013: 4
- FWCI
- 1.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Bioorganic & Medicinal Chemistry Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education (2013000014)
- Korea Institute of Science and Technology (2011-0009172)
- National Research Foundation of Korea
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Physical Sciences › Chemistry › Organic Chemistry › Synthesis and biological activity
- Keywords
- vascular endothelial growth factor, hypoxia-inducible factor-1α, P300, protein-protein interaction inhibition, small molecule inhibitors, tumor angiogenesis, transcriptional regulation, fluorescence polarization assay, HeLa cells, anticancer drug discovery
- MeSH terms
- Cell Survival, Fluorescence Polarization, HeLa Cells, Humans, Protein Binding, Transcription, Genetic, Protein Interaction Mapping, Vascular Endothelial Growth Factor A, E1A-Associated p300 Protein, Hypoxia-Inducible Factor 1, alpha Subunit, Small Molecule Libraries
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