title: BMS-182123, a fungal metabolite that inhibits the production of TNF-alpha by macrophages and monocytes.
abstract: A fungal metabolite, BMS-182123, which inhibited bacterial endotoxin-induced production of tumor necrosis factor (TNF-alpha) in murine macrophages and human peripheral blood monocytes (in vitro), was isolated from the culture broth of Penicillium chrysogenum strain V39673. The effective BMS-182123 concentration (IC50) resulting in 50% inhibition of lipopolysaccharide-induced TNF-alpha production in murine macrophages and human monocytes was 600 ng/ml and 4.0 microgram/ml, respectively. BMS-182123 suppressed the lipopolysaccharide-induced TNF-alpha promoter activity and did not affect the stability of posttranscriptional mRNA. Addition of hydrophobic resin, Amberlite XAD-8 (1%), to the fermentation enhanced the production of BMS-182123 by 5.5 fold. A total of 577 mg pure BMS-182123 was recovered from a 250-liter fermentation supplemented with 1% Amberlite XAD-8.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, Connecticut 06492, USA.
authors.forename: G A
authors.initials: GA
authors.lastname: Warr
authors.forename: J A
authors.initials: JA
authors.lastname: Veitch
authors.forename: A W
authors.initials: AW
authors.lastname: Walsh
authors.forename: G A
authors.initials: GA
authors.lastname: Hesler
authors.forename: D M
authors.initials: DM
authors.lastname: Pirnik
authors.forename: J E
authors.initials: JE
authors.lastname: Leet
authors.forename: P F
authors.initials: PF
authors.lastname: Lin
authors.forename: I A
authors.initials: IA
authors.lastname: Medina
authors.forename: K D
authors.initials: KD
authors.lastname: McBrien
authors.forename: S
authors.initials: S
authors.lastname: Forenza
authors.forename: J M
authors.initials: JM
authors.lastname: Clark
authors.forename: K S
authors.initials: KS
authors.lastname: Lam
mesh_terms: D000818:Animals; D001483:Base Sequence; D001952:Bridged-Ring Compounds / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D015342:DNA Probes / Q000235:genetics; D005285:Fermentation; D006801:Humans; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D010407:Penicillium / Q000145:classification / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D001952:Bridged-Ring Compounds; D015342:DNA Probes; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C099299:trichodimerol