Reveromycin A

• CAS: 134615-37-5
• Catalog Number: ACM134615375-2
• Category: Main Products
• Molecular Weight: 660.8
• Molecular Formula: C36H52O11
• Synonyms: (2E,6E,8E)-10-[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
• Boiling Point: 849.02 °C at 760 mmHg (Predicted)
• Appearance: Lyophilized

Case Study

Effects of Reveromycin A on Cell Death in Normal and Disease-Related Joint Cells

Svrcina, Haley, et al. Journal of Cellular Biochemistry, 2018, 119(6), 4382-4396.

Reveromycin A (Rev A), an antibiotic isolated from soil bacteria, induces osteoclast apoptosis via caspase 9 activation but does not induce necrosis after prolonged treatment. This work investigated the cell death effects of Rev A on normal and diseased joint cells. The data indicate that under acidic conditions, a physiological dose of Rev A prompts normal synoviocytes to undergo apoptosis, whereas pathological fibroblast-like synoviocytes exhibit resistance to both apoptosis and necrosis.
Evaluation methods and results
· At a physiological pH of 7.4 or an inflamed joint-mimicking pH of 6.8, a concentration of 10 μM Rev A does not trigger apoptosis or necrosis in normal chondrocytes. In contrast, normal synoviocytes do experience apoptosis at this concentration under acidic conditions, although the process is not mediated by caspase 8 or caspase 9. Fibroblast-like synoviocytes (FLS) derived from rheumatoid arthritis patients show resistance to apoptosis and necrosis induced by Rev A at both pH levels.
· Normal FLS also exhibit resistance to Rev A-induced apoptosis and necrosis at these pH levels; however, they do undergo apoptosis when exposed to 10 μM mitomycin C. To explore the underlying reasons for the differing effects of these two antibiotics on apoptosis, a structural analysis concerning their ability to permeate cell membranes was conducted. This comparative structure-activity analysis indicated that Rev A is less effective at traversing the cell membrane at near-neutral pH.

Co-Crystal Structure Study of Reveromycin A and Saccharomyces Cerevisiae IleRS (ScIleRS)

Chen, Bingyi, et al. Nature communications, 2021, 12(1), 1616.

Reveromycin A (RM-A) exhibits antifungal, anticancer, anti-bone metastasis, anti-periodontitis and anti-osteoporosis activities by selectively inhibiting eukaryotic cytoplasmic isoleucyl-tRNA synthetase (IleRS). This work studied the co-crystal structure of RM-A in complex with Saccharomyces cerevisiae IleRS (ScIleRS), and the results showed that the RM-A molecule mainly occupies the 3' CCA end binding site of tRNA^Ile.
Inhibitory mechanism of reveromycin A at the tRNA binding site
· The co-crystal structure revealed that RM-A binds to the 3' CCA end of tRNAIle within the catalytic domain of eukaryotic cytoplasmic IleRS, effectively preventing the productive interaction of tRNAIle with this domain. However, the alternative binding of tRNAIle to the editing domain of IleRS may remain unaffected. Additionally, RM-A might partially interfere with the phosphate groups of ATP. Conversely, the substrate l-isoleucine and the intermediate product Ile-AMP can simultaneously interact with RM-A within the aminoacylation pocket of IleRS.
· Given that class I aminoacyl-tRNA synthetases (AARSs) utilize the conserved Rossmann-fold catalytic domain for tRNA charging at the CCA end, the structural framework and inhibitory action of RM-A could be leveraged to design tRNA-site inhibitors for other class I AARSs. These inhibitors could be combined with compounds targeting different binding sites on the same enzyme or used together to address multiple AARSs, thereby potentially mitigating drug resistance.

Custom Q&A

What is the molecular formula of Reveromycin A?

The molecular formula of Reveromycin A is C36H52O11.

What are some synonyms for Reveromycin A?

Some synonyms for Reveromycin A are 134615-37-5 and CHEMBL332724.

What is the molecular weight of Reveromycin A?

The molecular weight of Reveromycin A is 660.8 g/mol.

When was Reveromycin A created?

Reveromycin A was created on October 25, 2006.

What is the structure of Reveromycin A?

The structure of Reveromycin A can be viewed in the reference link provided.

What is the IUPAC name of Reveromycin A?

The IUPAC name of Reveromycin A is (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.

What is the InChI of Reveromycin A?

The InChI of Reveromycin A is 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.

What is the InChIKey of Reveromycin A?

The InChIKey of Reveromycin A is ZESGNAJSBDILTB-OXVOKJAASA-N.

What is the CAS number of Reveromycin A?

The CAS number of Reveromycin A is 134615-37-5.

What is the ChEMBL ID of Reveromycin A?

The ChEMBL ID of Reveromycin A is CHEMBL332724.