| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 2mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
Silvestrol targets eukaryotic translation initiation factor 4A (eIF4A), an RNA helicase that is essential for cap-dependent translation initiation. By inhibiting eIF4A, silvestrol blocks the translation of mRNAs with highly structured 5' untranslated regions (UTRs), which often encode proteins involved in cancer cell survival, proliferation, and angiogenesis. This mechanism underlies its anticancer and antiviral activities.
|
|---|---|
| ln Vitro |
Translation inhibitors that specifically target eIF4A include silvestrol. With IC50 values ranging from 1 to 7 nM, silvestrol demonstrates strong cytotoxic action against numerous human cancer cell lines, including those from the prostate, breast, and lung [1]. LNCaP cell colonies were substantially fewer in number when sivestrol was used. Via the mitochondrial route, silvestrol (30 nM, 120 nM) causes apoptosis in LNCaP cells. Silvestrol-induced apoptosis involves Apaf-1, Caspase-2, Caspase-9, and Caspase-10, but not Apaf-3 or Caspase-7 [2]. Apoptosis and caspase-3 activation are induced by silvestrol in a dose- and time-dependent manner. In ATG7-null mouse embryonic fibroblasts (MEFs) deficient in functioning autophagy proteins, silvestrol-mediated cell death is reduced [3]. When compared to control cells, silvestrol (50 nM) causes nearly-static cell indices and an instantaneous inhibitory action. Higher doses of silvestrol (50 nM) decreased cell proliferation, whereas silvestrol (6.25 nM) increased proliferation more than vehicle control-treated cells. When combined with CDDP, silvestrol and episilvestrol exhibit synergistic effects [4].
Silvestrol exhibits significant cytotoxic activity against many human cancer cell lines, including lung, prostate, and breast cancer, with IC50 values ranging from 1 to 7 nM. The compound causes autophagy and caspase-mediated apoptosis in cancer cells. Its potent activity across multiple cancer types has made it a subject of intense investigation as an anticancer therapeutic. |
| ln Vivo |
B cells xenografted from mice do not produce less human IgG in response to silvestrol (1.5 mg/kg, ip). Comparing silvestrol to a vehicle, survival was considerably extended. None of the mice treated with silvestrol had such lymphocytic infiltrates in their spleens, and upon necropsy, the mice displayed no other obvious symptoms of lymphoma [5].
Silvestrol has shown promising in vivo activity against various cancer types, including leukemia, breast cancer, and pancreatic cancer. In animal models, silvestrol has demonstrated efficacy in reducing tumor growth. The compound has also shown antiviral activity in vivo against several viruses, including coronaviruses. Silvestrol is being actively investigated for its potential as an anticancer therapeutic agent. |
| Enzyme Assay |
eIF4A RNA helicase activity is assessed using in vitro helicase assays with purified recombinant eIF4A and RNA substrates. Silvestrol is incubated at various concentrations, and its ability to inhibit RNA unwinding is measured. Inhibition of translation is assessed using cell-free translation systems (e.g., rabbit reticulocyte lysate) with reporter mRNAs. IC50 values for translation inhibition are calculated.
|
| Cell Assay |
Cytotoxicity is evaluated using a panel of human cancer cell lines including lung, prostate, and breast cancer cells. Cells are exposed to silvestrol at various concentrations for 48-72 hours, and cell viability is measured using MTT, XTT, or CellTiter-Glo assays. IC50 values are calculated from dose-response curves. Autophagy is assessed by measuring LC3-II conversion or GFP-LC3 puncta formation. Apoptosis is evaluated by Annexin V/PI staining or caspase activity assays.
|
| Animal Protocol |
Silvestrol is administered intraperitoneally or orally in murine xenograft models of various cancers. Tumor-bearing mice are treated with silvestrol at various doses on a daily or every-other-day schedule. Tumor volumes are measured twice weekly, and body weight is monitored. At the end of the study, tumors are harvested for analysis of eIF4A inhibition and apoptosis markers. Antiviral efficacy is evaluated in animal models of viral infection.
|
| ADME/Pharmacokinetics |
Silvestrol has a molecular weight of 654.66 and molecular formula C34H38O13. Purity is typically ≥98%. The compound is a natural product derived from Aglaia foveolata. It is soluble in DMSO. Storage is recommended at -80°C for long-term stability. Silvestrol is a specific eIF4A-targeting translation inhibitor and is used as a research tool in cancer and virology.
|
| Toxicity/Toxicokinetics |
Preclinical toxicity studies of silvestrol have shown that it is tolerated at therapeutic doses in animal models. The primary mechanism-based toxicities may include effects on normal cells that rely on cap-dependent translation. However, the compound's selectivity for mRNAs with structured 5' UTRs may confer a therapeutic window. In antiviral studies, silvestrol has been used without significant adverse effects. Further toxicological characterization is needed for clinical development.
|
| References |
|
| Additional Infomation |
Silvestrol is an organic heterocyclic tricyclic compound with a structure comprising a 2,3,3a,8b-tetrahydro-H-benzo[b]cyclopentano[d]furan skeleton. This skeleton is substituted with hydroxyl groups at C-1 and C-8b, with a methoxycarbonyl group at C-2, a phenyl group at C-3, a 4-methoxyphenyl group at C-3a, a methoxy group at C-8, and a 1,4-dioxane-2-oxy group at C-6. The C-6 position is further substituted with both a methoxy group and a 1,2-dihydroxyethyl group. Silvestrol was isolated from wild Aglaia silvestris and possesses antitumor activity. It is both a plant metabolite and an antitumor drug. It is an organic heterocyclic tricyclic compound belonging to the dioxane, ether, and methyl ester classes. According to reports, Silvstrol has been found in both Aglaia foveolata and Aglaia silvestris, and relevant data is available for reference.
Silvestrol (CAS#: 697235-38-4) is a natural product derived from Aglaia foveolata belonging to the rocaglate family. It is a specific eIF4A-targeting translation inhibitor with potent cytotoxic activity against human cancer cell lines (IC50 1-7 nM) and broad-spectrum antiviral activity. Silvestrol causes autophagy and caspase-mediated apoptosis and is being investigated as an anticancer therapeutic. It is a valuable research tool for studying translation regulation, cancer biology, and viral infections. |
| Molecular Formula |
C34H38O13
|
|---|---|
| Molecular Weight |
654.6577
|
| Exact Mass |
654.231
|
| CAS # |
697235-38-4
|
| Related CAS # |
Silvestrol aglycone;960365-65-5;Episilvestrol;697235-39-5
|
| PubChem CID |
11787114
|
| Appearance |
White to off-white solid powder
|
| Density |
1.5±0.1 g/cm3
|
| Boiling Point |
800.8±65.0 °C at 760 mmHg
|
| Flash Point |
252.4±27.8 °C
|
| Vapour Pressure |
0.0±3.0 mmHg at 25°C
|
| Index of Refraction |
1.652
|
| LogP |
2.32
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
13
|
| Rotatable Bond Count |
11
|
| Heavy Atom Count |
47
|
| Complexity |
1050
|
| Defined Atom Stereocenter Count |
9
|
| SMILES |
CO[C@H]1[C@@H](O[C@H](CO1)[C@@H](CO)O)OC2=CC3=C(C(=C2)OC)[C@@]4([C@@H]([C@@H]([C@H]([C@@]4(O3)C5=CC=C(C=C5)OC)C6=CC=CC=C6)C(=O)OC)O)O
|
| InChi Key |
GVKXFVCXBFGBCD-QKDMMWSPSA-N
|
| InChi Code |
InChI=1S/C34H38O13/c1-40-20-12-10-19(11-13-20)34-27(18-8-6-5-7-9-18)26(30(38)42-3)29(37)33(34,39)28-23(41-2)14-21(15-24(28)47-34)45-32-31(43-4)44-17-25(46-32)22(36)16-35/h5-15,22,25-27,29,31-32,35-37,39H,16-17H2,1-4H3/t22-,25-,26-,27-,29-,31-,32-,33+,34+/m1/s1
|
| Chemical Name |
methyl (1R,2R,3S,3aR,8bS)-6-[[(2S,3R,6R)-6-[(1R)-1,2-dihydroxyethyl]-3-methoxy-1,4-dioxan-2-yl]oxy]-1,8b-dihydroxy-8-methoxy-3a-(4-methoxyphenyl)-3-phenyl-2,3-dihydro-1H-cyclopenta[b][1]benzofuran-2-carboxylate
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ≥ 6.6 mg/mL (~10.08 mM)
H2O : < 0.1 mg/mL |
|---|---|
| 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 | 1.5275 mL | 7.6376 mL | 15.2751 mL | |
| 5 mM | 0.3055 mL | 1.5275 mL | 3.0550 mL | |
| 10 mM | 0.1528 mL | 0.7638 mL | 1.5275 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA