Studies on novel HIF activators, A-503451s II: biological activities of A-503451A

In the course of our screening, we discovered a novel compound, A-503451A, as a potent hypoxia-inducible factor (HIF) activator. In human hepatocarcinoma HepG2 cells, A-503451A induced HIF-mediated luciferase reporter gene expression and stabilized HIF-1α protein. A-503451A increased the mRNA expres...

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Bibliographic Details
Published inJournal of antibiotics Vol. 69; no. 10; pp. 754 - 758
Main Authors Kobayashi, Hideki, Ohyama, Takao, Kitamura-Miyazaki, Michiko, Hirota-Takahata, Yuki, Ando, Osamu
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 01.10.2016
Subjects
13/95
631/154/1435/2163
631/80/86
Bacteriology
Biomedical and Life Sciences
Bioorganic Chemistry
Life Sciences
Medicinal Chemistry
Microbiology
Organic Chemistry
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Summary:In the course of our screening, we discovered a novel compound, A-503451A, as a potent hypoxia-inducible factor (HIF) activator. In human hepatocarcinoma HepG2 cells, A-503451A induced HIF-mediated luciferase reporter gene expression and stabilized HIF-1α protein. A-503451A increased the mRNA expression levels and the protein secretion of HIF-dependent genes, vascular endothelial growth factor and erythropoietin. Addition of excess ferric chloride to the culture medium suppressed the HIF-induction activity of A-503451A. A-503451A did not have iron-chelating activity in vitro , but decreased the intracellular labile iron pool concentration. These data indicate that A-503451A is a unique HIF activator.
ISSN:0021-8820
1881-1469
DOI:10.1038/ja.2016.20