BMS-192548, a tetracyclic binding inhibitor of neuropeptide Y receptors, from Aspergillus niger WB2346. I. Taxonomy, fermentation, isolation and biological activity.
During the screening of microbial fermentation extracts for their ability to inhibit the binding of 125I-peptid YY (PYY) to the neuropeptide Y (NPY) receptor using the scintillation proximity assay (SPA), BMS-192548 was isolated from the extract of Aspergillus niger WB2346 by bioassay-guided fractionation. BMS-192548 showed the inhibitory activity against 125I-PYY binding to SK-N-MC and SMS-KAN cells, which express NPY1 and NPY2 receptors, respectively, with IC50 values of 24 microM in Y1 and 27 microM in Y2 receptor binding. BMS-192548 demonstrated weak cytotoxicity against murine tumor cell line M-109 with an IC50 value of 240 microM.
D001234:Aspergillus niger; D005285:Fermentation; D009279:Naphthacenes / Q000302:isolation & purification* / Q000494:pharmacology; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014407:Tumor Cells, Cultured
C096925:BMS 192548; D009279:Naphthacenes; D017476:Receptors, Neuropeptide Y