title: Discovery of a VHL and HIF1α interaction inhibitor with in vivo angiogenic activity via structure-based virtual screening.
abstract: We describe herein compound 1, which is similar to many known natural products, as an inhibitor of the VHL-HIF1α interaction via structure-based virtual screening. Compound 1 disrupts VHL-mediated HIF1α degradation, leading to significantly increased VEGF expression. To our knowledge, compound 1 is a member of only the second class of small molecule inhibitors of the VHL-HIF1α interaction.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China. duncanleung@umac.mo.
authors.forename: Chao
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China. edmondma@hkbu.edu.hk.
authors.forename: Wanhe
authors.initials: W
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China. duncanleung@umac.mo.
authors.forename: Linmin
authors.initials: L
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China. duncanleung@umac.mo.
authors.forename: Jiaxin
authors.initials: J
authors.lastname: Liang
authors.affiliation: Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China. edmondma@hkbu.edu.hk.
authors.forename: Sheng
authors.initials: S
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China. duncanleung@umac.mo.
authors.forename: Ming-Yuen
authors.initials: MY
authors.lastname: Lee
authors.affiliation: Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China. edmondma@hkbu.edu.hk.
authors.forename: Dik-Lung
authors.initials: DL
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China. duncanleung@umac.mo.
authors.forename: Chung-Hang
authors.initials: CH
authors.lastname: Leung
mesh_terms: D030562:Databases, Protein; D057809:HEK293 Cells; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors*; D062105:Molecular Docking Simulation; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011487:Protein Conformation / Q000187:drug effects*; D060066:Protein Interaction Maps / Q000187:drug effects*; D054852:Small Molecule Libraries / Q000494:pharmacology*; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000037:antagonists & inhibitors*
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D054852:Small Molecule Libraries; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human