title: TMC-256A1 and C1, new inhibitors of IL-4 signal transduction produced by Aspergillus niger var niger TC 1629.
abstract: New inhibitors of IL-4 signal transduction, designated as TMC-256A1 and C1, were discovered together with TMC-256B1, a previously known dihydronaphthopyrone, from the fermentation broth of Aspergillus niger var niger TC 1629 by using an IL-4 driven reporter gene assay. Based on spectroscopic analyses, TMC-256A1 and C1 were found to be new members of the naphthopyrone antibiotics. TMC-256A1, B1 and C1 inhibited the IL-4 driven luciferase activity with IC50 values of 25 microM, 30 microM and 1.7 microM, respectively in this assay system. Furthermore, these compounds inhibited the expression of germline C epsilon mRNA with IC50 values of 6.6 microM , 34 microM and 0.31 microM, respectively.
authors.affiliation: Discovery Research Laboratory, Tanabe Seiyaku Co., Ltd., Toda-shi, Saitama, Japan. sakura@tanabe.co.jp
authors.forename: Masaaki
authors.initials: M
authors.lastname: Sakurai
authors.forename: Jun
authors.initials: J
authors.lastname: Kohno
authors.forename: Kouzou
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Toru
authors.initials: T
authors.lastname: Okuda
authors.forename: Maki
authors.initials: M
authors.lastname: Nishio
authors.forename: Kimio
authors.initials: K
authors.lastname: Kawano
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ohnuki
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001234:Aspergillus niger / Q000145:classification / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology; D002867:Chromones / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation; D009682:Magnetic Resonance Spectroscopy; D009281:Naphthalenes / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011753:Pyrones / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D000900:Anti-Bacterial Agents; D002867:Chromones; D009281:Naphthalenes; D011753:Pyrones; D012333:RNA, Messenger; C467209:TMC 256A1; C467210:TMC 256C1; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma; D008156:Luciferases