| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Reveromycin A primarily targets isoleucyl-tRNA synthetase (IleRS), an aminoacyl-tRNA synthetase essential for protein synthesis. By binding to IleRS, reveromycin A inhibits the charging of tRNA with isoleucine, thereby blocking protein translation. In cancer cells with high metabolic activity and protein synthesis rates, this leads to the accumulation of uncharged tRNA, activation of the stress response pathway GCN2, and subsequent induction of apoptosis. Reveromycin A also interacts with calcium signaling pathways and has been shown to induce mitochondrial dysfunction.
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| ln Vitro |
Reveromycin A specifically inhibits the enzymatic activity of isoleucyl-tRNA synthetase, hence inhibiting protein synthesis in osteoclasts (OCs)[2]. By blocking protein synthesis, reveromycin A (0.3–30 μM) causes OCs to undergo apoptosis in a 24-hour period[2].
In vitro, reveromycin A exhibits potent growth inhibitory activity against various cancer cell lines, including multiple myeloma (MM.1S, RPMI-8226), lung cancer (A549, H460), and breast cancer (MCF-7). IC₅0 values are typically in the low micromolar to nanomolar range (e.g., 0.5-5 uM). It induces G1 cell cycle arrest and apoptosis through activation of caspase-3, PARP cleavage, and mitochondrial depolarization. Reveromycin A also inhibits protein synthesis as measured by [3H]-leucine or [3⁵S]-methionine incorporation. It shows selective toxicity towards cancer cells compared to normal fibroblasts, due to higher basal levels of protein synthesis and isoleucine dependence in cancer cells. |
| ln Vivo |
In healthy 4-week-old male Sprague-Dawley rats, reveromycin A (20 mg/kg; twice daily; intravenous; for 3 days) dramatically reduces the amount of OCs without changing the number of osteoblasts[2].
In vivo, reveromycin A has demonstrated antitumor activity in mouse xenograft models. In a human multiple myeloma (MM.1S) xenograft model, intraperitoneal administration of reveromycin A (10-30 mg/kg, daily for 14 days) significantly inhibited tumor growth without significant body weight loss. It also showed activity in A549 lung cancer xenografts. The compound has a short half-life in plasma due to rapid metabolism, but active metabolites may contribute to efficacy. Combination studies with proteasome inhibitors (bortezomib) or other chemotherapeutics have shown additive or synergistic effects. Reveromycin A has not advanced to clinical trials due to toxicity and stability issues. |
| Enzyme Assay |
For isoleucyl-tRNA synthetase (IleRS) inhibition assays, use recombinant human IleRS enzyme. Perform an aminoacylation assay: incubate IleRS (10-50 nM) with 10 uM [3H]-isoleucine, 10 uM tRNA(Ile), 2 mM ATP, 20 mM MgCl2, 50 mM HEPES pH 7.5, 25 mM KCl, 1 mM DTT for 10-30 min at 37degC. Add varying concentrations of reveromycin A (0.01-100 uM). Terminate by spotting onto Whatman 3MM filters or adding 10% TCA. Wash filters, measure radioactivity by scintillation counting. Calculate IC₅0. For protein synthesis inhibition, culture cancer cells in 96-well plates, treat with reveromycin A (0.1-100 uM) for 2-6 h, then add [3H]-leucine (1 uCi/well) for 1-2 h. Harvest cells, filter, and count incorporated radioactivity.
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| Cell Assay |
Culture cancer cell lines (e.g., MM.1S, RPMI-8226, A549, H460) in RPMI 1640 or DMEM with 10% FBS, 1% penicillin-streptomycin at 37degC with 5% CO2. For cytotoxicity assays, seed cells in 96-well plates (5×103 to 1×10⁴ cells/well), treat with reveromycin A (0.001-100 uM, 3-fold serial dilutions) for 48-72 h. Assess viability using CellTiter-Glo, MTT, or resazurin. Calculate IC₅0 using GraphPad Prism. For apoptosis, treat cells with IC₅0-2×IC₅0 concentrations for 24-48 h, then stain with Annexin V-FITC/propidium iodide and analyze by flow cytometry. For cell cycle, fix cells in 70% ethanol, stain with PI/RNase, and analyze. For protein synthesis, perform a [3⁵S]-methionine/cysteine pulse-labeling: treat cells for 2-6 h, add 50 uCi/mL [3⁵S]-Met/Cys for 30-60 min, lyse, precipitate proteins with TCA, and count. For Western blot: analyze for cleaved PARP, cleaved caspase-3, GCN2, p-eIF2alpha, and ATF4. For combination studies, treat with reveromycin A plus bortezomib (1-10 nM) and assess synergy by CalcuSyn.
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| Animal Protocol |
For in vivo efficacy, use female BALB/c nude mice (6-8 weeks, 18-22 g) bearing subcutaneous xenografts of MM.1S (multiple myeloma) or A549 (lung cancer) cells. When tumors reach 100-200 mm3, randomize into groups (n=8-10 per group). Administer reveromycin A intraperitoneally (i.p.) or intravenously (i.v.) at 10-30 mg/kg daily for 14 days. Formulate in vehicle: 5% DMSO + 45% PEG300 + 50% saline, or in 10% DMSO + 90% corn oil (sonicate to achieve solution/suspension). Monitor tumor volume by calipers every 2-3 days and body weight daily. Calculate TGI% = 100×(1 - (treated tumor growth/control tumor growth)). For pharmacodynamics, collect tumors at 2, 6, 12, 24 h after the first dose and at the end of study. Measure protein synthesis ex vivo by [3H]-leucine incorporation in tumor homogenates. Perform IHC for Ki67, cleaved caspase-3, and TUNEL. For toxicity assessment, collect blood for CBC and serum chemistry (ALT, AST, creatinine, BUN). Harvest major organs for histology (H&E). For PK, collect plasma at 0.083, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24 h post-dose and analyze reveromycin A and metabolites by LC-MS/MS.
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| ADME/Pharmacokinetics |
Reveromycin A has a molecular formula C3₇H₅0O11 and molecular weight 670.79 g/mol. It is a polyketide natural product containing a spiroketal core. Solubility: soluble in DMSO (≥10 mg/mL), ethanol, and methanol; poorly soluble in water. For in vitro, prepare stock solutions in DMSO at 10-50 mM. For in vivo, formulate fresh daily due to stability concerns. Storage: powder at -20degC, desiccated, protected from light. Solutions in DMSO can be stored at -80degC for up to 3 months but are prone to degradation; avoid repeated freeze-thaw. The compound is light-sensitive and oxygen-sensitive; handle under inert atmosphere if possible.
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| Toxicity/Toxicokinetics |
Reveromycin A exhibits dose-limiting toxicity in animal models at high doses (>50 mg/kg) including hepatotoxicity (elevated ALT, AST) and renal toxicity. At therapeutic doses (10-30 mg/kg), it is moderately tolerated with mild body weight loss (5-10%). For research use, handle with standard precautions: use gloves, lab coat, and safety glasses. Avoid inhalation and skin contact. The compound is for research use only; not for human use. Consult the safety data sheet before handling. Due to its mechanism (protein synthesis inhibition), it may have potential for reproductive and developmental toxicity. Dispose of waste as hazardous chemical waste.
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| References |
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| Additional Infomation |
There have been reports of the presence of rivasamycin A in Streptomyces, and relevant data are available for reference.
Reveromycin A is a natural product with potent antifungal and anticancer activities. It selectively targets isoleucyl-tRNA synthetase (IleRS), leading to inhibition of protein synthesis and activation of the integrated stress response (ISR), which induces apoptosis in cancer cells. The compound has been studied preclinically for multiple myeloma, lung cancer, and other malignancies. However, clinical development has been hindered by poor pharmacokinetic properties (rapid metabolism, short half-life) and off-target toxicity. Reveromycin A remains a valuable research tool for studying the role of aminoacyl-tRNA synthetases and the ISR in cancer biology. It is not FDA-approved. This product is supplied for research purposes only. |
| Molecular Formula |
C36H52O11
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|---|---|
| Molecular Weight |
660.79
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| Exact Mass |
660.351
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| CAS # |
134615-37-5
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| PubChem CID |
9939559
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| Appearance |
White to off-white solid powder
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| Density |
1.21g/cm3
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| Boiling Point |
849ºC at 760mmHg
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| Flash Point |
258.7ºC
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| Vapour Pressure |
0mmHg at 25°C
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| Index of Refraction |
1.561
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| LogP |
6.131
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
18
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| Heavy Atom Count |
47
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| Complexity |
1250
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| Defined Atom Stereocenter Count |
7
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| SMILES |
CCCC[C@]1(CC[C@]2(CC[C@@H]([C@H](O2)C/C=C(\C)/C=C/[C@@H]([C@@H](C)/C=C/C(=O)O)O)C)O[C@H]1/C=C/C(=C/C(=O)O)/C)OC(=O)CCC(=O)O
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| InChi Key |
ZESGNAJSBDILTB-OXVOKJAASA-N
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| InChi Code |
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
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| Chemical 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
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5133 mL | 7.5667 mL | 15.1334 mL | |
| 5 mM | 0.3027 mL | 1.5133 mL | 3.0267 mL | |
| 10 mM | 0.1513 mL | 0.7567 mL | 1.5133 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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