BMS-192548
* Please be kindly noted products are not for therapeutic use. We do not sell to patients.
| Category | Enzyme inhibitors |
| Catalog number | BBF-03253 |
| CAS | 156368-93-3 |
| Molecular Weight | 414.36 |
| Molecular Formula | C21H18O9 |
Online Inquiry
Description
BMS-192548 is a neuropeptide Y (NPY) receptor binding inhibitor produced by Aspergillus niger WB2346. It also has weak cytotoxicity, with an IC50 of 240 µmol/L for murine tumor cells M-109.
Specification
| Synonyms | TAN-1612 |
| IUPAC Name | 3-acetyl-4,4a,6,7,12a-pentahydroxy-9-methoxy-1,12-dihydrotetracene-2,5-dione |
| Canonical SMILES | CC(=O)C1=C(C2(C(=O)C3=C(C4=C(C=C(C=C4C=C3CC2(CC1=O)O)OC)O)O)O)O |
| InChI | InChI=1S/C21H18O9/c1-8(22)14-13(24)7-20(28)6-10-3-9-4-11(30-2)5-12(23)15(9)17(25)16(10)19(27)21(20,29)18(14)26/h3-5,23,25-26,28-29H,6-7H2,1-2H3 |
| InChI Key | GEIAHRUFSQGALU-UHFFFAOYSA-N |
Properties
| Appearance | Yellow Crystal |
| Boiling Point | 811.4±0.0°C at 760 mmHg |
| Melting Point | 254°C(dec.) |
| Density | 1.7±0.0 g/cm3 |
Reference Reading
1. BMS-192548, a tetracyclic binding inhibitor of neuropeptide Y receptors, from Aspergillus niger WB2346. I. Taxonomy, fermentation, isolation and biological activity
K Kodukula, M Arcuri, J Q Cutrone, R M Hugill, S E Lowe, D M Pirnik, Y Z Shu, P B Fernandes, R Seethala J Antibiot (Tokyo). 1995 Oct;48(10):1055-9. doi: 10.7164/antibiotics.48.1055.
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.
2. BMS-192548, a tetracyclic binding inhibitor of neuropeptide Y receptors, from Aspergillus niger WB2346. II. Physico-chemical properties and structural characterization
Y Z Shu, J Q Cutrone, S E Klohr, S Huang J Antibiot (Tokyo). 1995 Oct;48(10):1060-5. doi: 10.7164/antibiotics.48.1060.
The structure of BMS-192548, a tetracyclic binding inhibitor of neuropeptide Y receptors, was established by spectroscopic methods. The compound has an unusual B-C-D ring beta-diketone moiety.
3. Comparative characterization of fungal anthracenone and naphthacenedione biosynthetic pathways reveals an α-hydroxylation-dependent Claisen-like cyclization catalyzed by a dimanganese thioesterase
Yanran Li, Yit-Heng Chooi, Yuewei Sheng, Joan S Valentine, Yi Tang J Am Chem Soc. 2011 Oct 5;133(39):15773-85. doi: 10.1021/ja206906d. Epub 2011 Sep 14.
The linear tetracyclic TAN-1612 (1) and BMS-192548 (2) were isolated from different filamentous fungal strains and have been examined as potential neuropeptide Y and neurokinin-1 receptor antagonists, respectively. Although the biosynthesis of fungal aromatic polyketides has attracted much interest in recent years, the biosynthetic mechanism for such naphthacenedione-containing products has not been established. Using a targeted genome mining approach, we first located the ada gene cluster responsible for the biosynthesis of 1 in Aspergillus niger ATCC 1015. The connection between 1 and the ada pathway was verified through overexpression of the Zn(2)Cys(6)-type pathway-specific transcriptional regulator AdaR and subsequent gene expression analysis. The enzymes encoded in the ada gene cluster share high sequence similarities to the known apt pathway linked to the biosynthesis of anthraquinone asperthecin 3. Subsequent comparative investigation of these two highly homologous gene clusters by heterologous pathway reconstitution in Saccharomyces cerevisiae revealed a novel α-hydroxylation-dependent Claisen cyclization cascade, which involves a flavin-dependent monooxygenase that hydroxylates the α-carbon of an acyl carrier protein-bound polyketide and a bifunctional metallo-β-lactamase-type thioesterase (MβL-TE). The bifunctional MβL-TE catalyzes the fourth ring cyclization to afford the naphthacenedione scaffold upon α-hydroxylation, whereas it performs hydrolytic release of an anthracenone product in the absence of α-hydroxylation. Through in vitro biochemical characterizations and metal analyses, we verified that the apt MβL-TE is a dimanganese enzyme and requires both Mn(2+) cations for the observed activities. The MβL-TE is the first example of a thioesterase in polyketide biosynthesis that catalyzes the Claisen-like condensation without an α/β hydrolase fold and forms no covalent bond with the substrate. These mechanistic features should be general to the biosynthesis of tetracyclic naphthacenedione compounds in fungi.
Recommended Products
| BBF-01825 | Loganin | Inquiry |
| BBF-03754 | CASTANOSPERMINE | Inquiry |
| BBF-02614 | Nystatin | Inquiry |
| BBF-05862 | Epirubicin | Inquiry |
| BBF-01693 | Doxorubicin EP Impurity A (Daunorubicin) | Inquiry |
| BBF-02642 | Lactonamycin | Inquiry |
Bio Calculators
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
* Total Molecular Weight:
g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
