Reveromycin A
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| Category | Enzyme inhibitors |
| Catalog number | BBF-04647 |
| CAS | 134615-37-5 |
| Molecular Weight | 660.79 |
| Molecular Formula | C36H52O11 |
| Purity | >99% by HPLC |
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Description
The dominant analogue of complex of spiroketals isolated from streptomyces sp. It is an inhibitor of the mitogenic activity of EGF and a G1 phase cell cycle inhibitor. It selectively inhibits isoleucyl-trna synthetase. It has anti-proliferation effect on human cell lines KB and K562, and has potent antifungal activity.
Specification
| Synonyms | (-)-Reveromycin A; [2S-[2α(1E,3E),3β,6α[8S*(2E,4E,6R*,7R*,8E),9R*]]]-butanedioic acid mono[3-butyl-8-(9-carboxy-6-hydroxy-3,7-dimethyl-2,4,8-nonatrienyl)-2-(4-carboxy-3-methyl-1,3-butadienyl)-9-methyl-1,7-dioxaspiro[5.5]undec-3-yl] Ester; Butanedioic Acid Mono[(2S,3R,6S,8R,9S)-3-butyl-8-[(2E,4E,6S,7S,8E)-9-carboxy-6-hydroxy-3,7-dimethyl-2,4,8-nonatrienyl]-2-[(1E,3E)-4-carboxy-3-methyl-1,3-butadienyl]-9-methyl-1,7-dioxaspiro[5.5]undec-3-yl] Ester |
| Storage | Store at -20°C |
| IUPAC Name | (2E,4S,5S,6E,8E)-10-[(2S,3R,6S,8R,9S)-3-butyl-2-[(1E,3E)-4-carboxy-3-methylbuta-1,3-dienyl]-3-(3-carboxypropanoyloxy)-9-methyl-1,7-dioxaspiro[5.5]undecan-8-yl]-5-hydroxy-4,8-dimethyldeca-2,6,8-trienoic acid |
| Canonical SMILES | CCCCC1(CCC2(CCC(C(O2)CC=C(C)C=CC(C(C)C=CC(=O)O)O)C)OC1C=CC(=CC(=O)O)C)OC(=O)CCC(=O)O |
| InChI | InChI=1S/C36H52O11/c1-6-7-19-35(47-34(44)17-16-32(40)41)21-22-36(46-30(35)14-10-25(3)23-33(42)43)20-18-27(5)29(45-36)13-9-24(2)8-12-28(37)26(4)11-15-31(38)39/h8-12,14-15,23,26-30,37H,6-7,13,16-22H2,1-5H3,(H,38,39)(H,40,41)(H,42,43)/b12-8+,14-10+,15-11+,24-9+,25-23+/t26-,27-,28-,29+,30-,35+,36-/m0/s1 |
| InChI Key | ZESGNAJSBDILTB-OXVOKJAASA-N |
| Source | Streptomyces sp. |
Properties
| Appearance | Tan Solid |
| Antibiotic Activity Spectrum | Neoplastics (Tumor); Fungi |
| Boiling Point | 849.0±65.0°C (Predicted) |
| Density | 1.21±0.1 g/cm3 (Predicted) |
| Solubility | Soluble in Ethanol, Methanol, DMF, DMSO; Poorly soluble in Water |
Reference Reading
1. Reveromycin A inhibits osteolytic bone metastasis of small-cell lung cancer cells, SBC-5, through an antiosteoclastic activity
Hiroaki Muguruma, Saburo Sone, Hisanori Uehara, Seiji Yano, Soji Kakiuchi, Hiroyuki Osada, Makoto Kawatani Clin Cancer Res . 2005 Dec 15;11(24 Pt 1):8822-8. doi: 10.1158/1078-0432.CCR-05-1335.
Purpose:The purpose of this study was to determine therapeutic effect of a novel antibiotic, reveromycin A, against osteolytic bone metastasis of human small cell lung cancer (SBC-5) cells.Results:Reveromycin A induced apoptosis specifically in osteoclasts in vitro. Although reveromycin A did not inhibit SBC-5 cell proliferation, it suppressed the expression of parathyroid hormone-related peptide. Intravenous inoculation of SBC-5 cells in natural killer cell-depleted severe combined immunodeficient mice produced experimental metastases in multiple organs, including the bone. Daily administration of reveromycin A inhibited the bone metastasis, but not visceral metastasis, in a dose-dependent manner. Histologic analyses revealed that although treatment with reveromycin A did not affect the number of proliferating tumor cells, it decreased the number of osteoclasts and increased apoptotic cells in bone lesions.Conclusions:These findings suggest that reveromycin A may inhibit osteolytic bone metastasis through suppression of osteoclast activity by directly inducing apoptosis and indirectly inhibiting tumor cell-derived parathyroid hormone-related peptide production. Therefore, reveromycin A may be a novel, potent therapeutic agent against osteolytic bone metastasis of lung cancer in humans.
2. Reveromycin A-Induced Apoptosis in Osteoclasts Is Not Accompanied by Necrosis
Megan Gragg, Brittany Mead, Tyler Derr, Jonathan Stofer, David Collins, Chris Sloan, Heather Morgan, Kaitlin Riemann, Emily Heller, Laura Tedeschi, Daniel Jones, Paul Landis, Spenser Lang, Nathan Linna, Cory Hines, Alyssa Mann-Knowlton J Cell Biochem . 2015 Aug;116(8):1646-57. doi: 10.1002/jcb.25125.
Reveromycin A (RM-A), a small natural product isolated from Streptomyces bacteria, is a potential osteoporosis therapeutic in that it specifically induces apoptosis in osteoclasts but not osteoblasts. The purpose of the study presented here was to further elucidate the intracellular mechanisms of RM-A death effects in mature osteoclasts. A specific clone of RAW264.7 murine macrophages that was previously characterized for its ability to acquire an osteoclast nature on differentiation was differentiated in the presence of receptor activator of nuclear factor kappa B ligand (RANKL). Subsequent staining was performed for tartrate-resistant acid phosphatase to confirm their osteoclast character. These osteoclasts were treated with ten micromolar RM-A for 2, 4, 6, 24, and 48 h at a pH of 5.5. Peak apoptosis induction occurred at 4-6 h as measured by caspase 3 activity. Lactate dehydrogenase release assay revealed no significant RM-A-induced necrosis. Western blot analysis of cytoplasmic extracts demonstrated activation of caspase 9 (2.3-fold at 2 h and 2.6-fold at 4 h, each P < 0.05) and no significant changes in Bcl-XL . In nuclear extracts, NFκB levels significantly increased on differentiation with RANKL but then remained constant through RM-A treatment. Over the extended time course studied, RM-A-induced apoptosis in osteoclasts was not accompanied by necrosis, suggesting that RM-A would likely have limited effects on immediate, neighboring bone cell types. This specific cell death profile is promising for potential clinical investigations of RM-A as a bone antiresorptive.
3. Does local injection of reveromycin A inhibit tooth movement without causing systemic side effects?
Yuki Aoki, Fumika Kimura, Shunsuke Kako, Shigemi Goto, Makoto Kawatani, Ken Miyazawa, Hatsuhiko Maeda, Yuichiro Asano, Hiroyuki Osada, Chisato Minamoto, Masako Tabuchi, Miyuki Tanaka, Takuma Sato Eur J Orthod . 2021 Dec 1;43(6):658-664. doi: 10.1093/ejo/cjaa067.
Objective:To determine the feasibility of local inhibition of osteoclast activity and control of tooth movement with local intraoral reveromycin A (RMA) injection in model mice for experimental tooth movement.Materials and methods:Eight-week-old wild-type mice (n = 6 per group) were divided into four groups consisting of two non-RMA groups that received normal saline for 14 (14-day non-RMA group) or 21 consecutive days (21-day non-RMA group) and 2 RMA groups that received RMA (1.0 mg/kg of weight) for 14 (14-day RMA group) or 21 consecutive days (21-day RMA group). RMA was injected locally into the buccal mucosa of the left first maxillary molar twice daily starting 3 days before placement of the 10-gf Ni-Ti closed coil spring. Tooth movement distance was analysed using micro-computed tomography. The effects on surrounding alveolar bone were evaluated by measuring the ratio of bone surface area to tissue surface area with haematoxylin-eosin-stained sections and counting the number of osteoclasts in periodontal tissue with TRAP-stained sections. Blood tests were performed and bone volume and trabecular separation at the tibial neck were measured to analyse systemic side effects.Results:Local RMA injection inhibited tooth movement by 40.6 per cent, promoted alveolar bone volume maintenance by 37.4 per cent, and inhibited osteoclast activity around the tooth root at 21 days by 40.8 per cent. Systemic effects on osteoclasts or osteoblasts were not observed.Conclusion:Local injection of RMA enabled control of tooth movement without systemic side effects in a mouse model.
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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 ╳
