BMS-182123, a fungal metabolite that inhibits the production of TNF-alpha by macrophages and monocytes.
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.
Warr
G A
GA
Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, Connecticut 06492, USA.
Veitch
J A
JA
Walsh
A W
AW
Hesler
G A
GA
Pirnik
D M
DM
Leet
J E
JE
Lin
P F
PF
Medina
I A
IA
McBrien
K D
KD
Forenza
S
S
Clark
J M
JM
Lam
K S
KS
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
D001952:Bridged-Ring Compounds; D015342:DNA Probes; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C099299:trichodimerol