Synthesis and structure-activity relationship study of chemical probes as hypoxia induced factor-1α/malate dehydrogenase 2 inhibitors = HIF-1/MDH2 저해제로서 화학 프로브의 합성 및 활성 구조 상관관계

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dc.contributor.authorR Naik-
dc.contributor.authorMi Sun Won-
dc.contributor.authorHyun Seung Ban-
dc.contributor.authorD Bhattarai-
dc.contributor.authorX Xu-
dc.contributor.authorY Eo-
dc.contributor.authorYe Seul Hong-
dc.contributor.authorS Singh-
dc.contributor.authorY Choi-
dc.contributor.authorH C Ahn-
dc.contributor.authorK Lee-
dc.date.accessioned2017-04-19T09:59:23Z-
dc.date.available2017-04-19T09:59:23Z-
dc.date.issued2014-
dc.identifier.issn00222623-
dc.identifier.uri10.1021/jm501241gko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/12316-
dc.description.abstractA structure-activity relationship study of hypoxia inducible factor-1α inhibitor 3-aminobenzoic acid-based chemical probes, which were previously identified to bind to mitochondrial malate dehydrogenase 2, was performed to provide a better understanding of the pharmacological effects of LW6 and its relation to hypoxia inducible factor-1α (HIF-1α) and malate dehydrogenase 2 (MDH2). A variety of multifunctional probes including the benzophenone or the trifluoromethyl diazirine for photoaffinity labeling and click reaction were prepared and evaluated for their biological activity using a cell-based HRE-luciferase assay as well as a MDH2 assay in human colorectal cancer HCT116 cells. Among them, the diazirine probe 4a showed strong inhibitory activity against both HIF-1α and MDH2. Significantly, the inhibitory effect of the probes on HIF-1α activity was consistent with that of the MDH2 enzyme assay, which was further confirmed by the effect on in vitro binding activity to recombinant human MDH2, oxygen consumption, ATP production, and AMP activated protein kinase (AMPK) activation. Competitive binding modes of LW6 and probe 4a to MDH2 were also demonstrated.-
dc.publisherAmer Chem Soc-
dc.titleSynthesis and structure-activity relationship study of chemical probes as hypoxia induced factor-1α/malate dehydrogenase 2 inhibitors = HIF-1/MDH2 저해제로서 화학 프로브의 합성 및 활성 구조 상관관계-
dc.title.alternativeSynthesis and structure-activity relationship study of chemical probes as hypoxia induced factor-1α/malate dehydrogenase 2 inhibitors-
dc.typeArticle-
dc.citation.titleJournal of Medicinal Chemistry-
dc.citation.number22-
dc.citation.endPage9538-
dc.citation.startPage9522-
dc.citation.volume57-
dc.contributor.affiliatedAuthorMi Sun Won-
dc.contributor.affiliatedAuthorHyun Seung Ban-
dc.contributor.alternativeNameNaik-
dc.contributor.alternativeName원미선-
dc.contributor.alternativeName반현승-
dc.contributor.alternativeNameBhattarai-
dc.contributor.alternativeNameXu-
dc.contributor.alternativeName어유미-
dc.contributor.alternativeName홍예슬-
dc.contributor.alternativeNameSingh-
dc.contributor.alternativeName최용석-
dc.contributor.alternativeName안희철-
dc.contributor.alternativeName이경-
dc.identifier.bibliographicCitationJournal of Medicinal Chemistry, vol. 57, no. 22, pp. 9522-9538-
dc.identifier.doi10.1021/jm501241g-
dc.description.journalClassY-
Appears in Collections:
Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
Division of Biomedical Research > Biotherapeutics Translational Research Center > 1. Journal Articles
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