title: A new anti-angiogenic small molecule, G0811, inhibits angiogenesis via targeting hypoxia inducible factor (HIF)-1α signal transduction.
abstract: Regulation of hypoxia inducible factor (HIF)-1α stabilization, which in turn contributes to adaptation of tumor cells to hypoxia has been highlighted as a promising therapeutic target in angiogenesis-related diseases. We have identified a new small molecule, G0811, as a potent angiogenesis inhibitor that targets HIF-1α signal transduction. G0811 suppressed HIF-1α stability in cancer cells and inhibited in vitro and in vivo angiogenesis, as validated by tube formation, chemoinvasion, and chorioallantoic membrane (CAM) assays. In addition, G0811 effectively decreased the expression of vascular endothelial growth factor (VEGF), which is one of target genes of HIF-1α. However, G0811 did not exhibit anti-proliferative activities or toxicity in human umbilical vein endothelial cells (HUVECs) at effective doses. These results demonstrate that G0811 could be a new angiogenesis inhibitor that acts by targeting HIF-1α signal transduction pathway.
authors.affiliation: Chemical Genomics National Research Laboratory, Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science & Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Ki Hyun
authors.initials: KH
authors.lastname: Kim
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Jung
authors.forename: Ho Jeong
authors.initials: HJ
authors.lastname: Kwon
mesh_terms: D000726:Androgen Antagonists / Q000737:chemistry / Q000494:pharmacology*; D001572:Benzofurans / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D009369:Neoplasms / Q000098:blood supply; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D055550:Protein Stability / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D000726:Androgen Antagonists; D001572:Benzofurans; D017077:Culture Media, Conditioned; C585661:G0811 compound; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D013449:Sulfonamides; D042461:Vascular Endothelial Growth Factor A
keywords: Angiogenesis; Hypoxia inducible factor (HIF)-1α; Small molecule; VEGF