Biological activity of a novel nonpeptide antagonist to the interleukin-6 receptor 20S,21-epoxy-resibufogenin-3-formate

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dc.contributor.authorM Hayashi-
dc.contributor.authorMun Chual Rho-
dc.contributor.authorA Fukami-
dc.contributor.authorA Enomoto-
dc.contributor.authorS Nonaka-
dc.contributor.authorY Sekiguchi-
dc.contributor.authorT Yanagisawa-
dc.contributor.authorA Yamashita-
dc.contributor.authorT Nogawa-
dc.contributor.authorY Kamano-
dc.contributor.authorK Komiyama-
dc.date.accessioned2017-04-19T08:59:23Z-
dc.date.available2017-04-19T08:59:23Z-
dc.date.issued2002-
dc.identifier.issn0022-3565-
dc.identifier.uri10.1124/jpet.102.036137ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/5962-
dc.description.abstractInterleukin (IL)-6 is a key mediator in the regulation and coordination of the immune response and participates in pathogenesis of cancer cachexia, autoimmune disease, and postmenopausal osteoporosis. In the course of a screening program aimed at IL-6 inhibitor from natural products, we isolated 20S,21-epoxy-resibufogenin-3-formate (ERBF) from bufadienolide and examined the effect of ERBF on activities of various cytokines. ERBF dose dependently suppressed IL-6 activity and caused a parallel rightward shift of dose-response curves to IL-6 at concentrations of 0.03 to 10 ng/ml. Analysis of data yields a pA2 of 5.12 and a slope of 0.99. Selectivity of ERBF on activity of cytokines was examined using cytokine-dependent cell lines. ERBF did not affect IL-2-dependent growth of CTLL-2 cells, IL-3-dependent growth of Baf3 cells, or tumor necrosis factor (TNF)α-induced growth suppression in TNFα-sensitive L929 cells. ERBF also did not affect IL-4-stimulated expression of FcεR II receptor (CD23) in U-937 cells, the IL-8-induced chemotaxis of human neutrophils, or nerve growth factor-stimulated neuronal differentiation in PC-12 cells. In contrast, ERBF dose dependently suppressed IL-6-induced neuronal differentiation in PC-12 cells. Furthermore, ERBF suppressed only IL-6-induced osteoclast formation without affecting osteoclast formation induced by IL-11, leukemia inhibitory factor, and 1α,25-dihydroxyvitamin D3. In receptor binding assay, unbound (free) IL-6 was increased in a dose-dependent manner by pretreatment with ERBF on IL-6 receptor (IL-6R), suggesting that ERBF suppresses binding of IL-6 to IL-6R. These results clearly indicate that ERBF is a novel specific small molecule to show IL-6 receptor antagonist activity.-
dc.publisherAmer Soc Pharmacology Experimental Therapeutics-
dc.titleBiological activity of a novel nonpeptide antagonist to the interleukin-6 receptor 20S,21-epoxy-resibufogenin-3-formate-
dc.title.alternativeBiological activity of a novel nonpeptide antagonist to the interleukin-6 receptor 20S,21-epoxy-resibufogenin-3-formate-
dc.typeArticle-
dc.citation.titleJournal of Pharmacology and Experimental Therapeutics-
dc.citation.number1-
dc.citation.endPage109-
dc.citation.startPage104-
dc.citation.volume303-
dc.contributor.affiliatedAuthorMun Chual Rho-
dc.contributor.alternativeNameHayashi-
dc.contributor.alternativeName노문철-
dc.contributor.alternativeNameFukami-
dc.contributor.alternativeNameEnomoto-
dc.contributor.alternativeNameNonaka-
dc.contributor.alternativeNameSekiguchi-
dc.contributor.alternativeNameYanagisawa-
dc.contributor.alternativeNameYamashita-
dc.contributor.alternativeNameNogawa-
dc.contributor.alternativeNameKamano-
dc.contributor.alternativeNameKomiyama-
dc.identifier.bibliographicCitationJournal of Pharmacology and Experimental Therapeutics, vol. 303, no. 1, pp. 104-109-
dc.identifier.doi10.1124/jpet.102.036137-
dc.description.journalClassY-
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Jeonbuk Branch Institute > Functional Biomaterial Research Center > 1. Journal Articles
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