| Size | Price | Stock | Qty |
|---|---|---|---|
| 500mg |
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| 1g |
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| Other Sizes |
| Targets |
eIF4A[1]
eIF4AI and eIF4AII, which are ATP-dependent RNA helicases essential for cap-dependent translation initiation. eIF4A3-IN-5 inhibits the helicase activity of these initiation factors, thereby blocking the translation of mRNAs that have long and structured 5' untranslated regions (UTRs). |
|---|---|
| ln Vitro |
eIF4A3-IN-5 has demonstrated potent inhibitory activity against eIF4AI and eIF4AII in biochemical assays. It has the potential for the research of eIF4A dependent diseases, including cancer.
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| ln Vivo |
No specific in vivo activity data has been reported. As a translation inhibitor with potential anticancer effects, it would be studied in tumor xenograft models, where it is expected to reduce the expression of oncogenic proteins with complex 5'UTRs, leading to tumor growth suppression.
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| Enzyme Assay |
A typical protocol for evaluating eIF4A inhibition involves a helicase assay. Recombinant eIF4AI is incubated with a fluorescently labeled RNA substrate in a buffer (25 mM HEPES, pH 7.5, 50 mM KCl, 2.5 mM MgCl2, 2 mM DTT) with varying concentrations of eIF4A3-IN-5 (0.1 nM-10 uM). The reaction is initiated by adding 2 mM ATP, and after 30 minutes at 37degC, the helicase activity is measured by a decrease in fluorescence polarization. The IC50 value is determined by plotting inhibition against compound concentration.
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| Cell Assay |
For in vitro studies, cancer cell lines (e.g., HeLa or MCF-7) are seeded in 96-well plates at 5,000 cells/well. After 24 hours, cells are treated with eIF4A3-IN-5 at concentrations ranging from 0.1-50 uM for 48-72 hours. Cell viability is assessed using the MTT assay. To measure translation inhibition, cells are treated for 6-24 hours, and newly synthesized proteins are labeled with 35S-methionine, followed by SDS-PAGE and autoradiography. Apoptosis is measured by caspase-3/7 activity or Annexin V-FITC staining.
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| Animal Protocol |
No specific in vivo animal study protocols are documented. Based on compounds with a similar mechanism, a typical protocol would involve establishing subcutaneous tumor xenografts in 6-8 week old female BALB/c nude mice. Once tumors reach 100-150 mm3, eIF4A3-IN-5 would be administered via intraperitoneal (i.p.) or oral gavage at doses of 10-50 mg/kg, daily for 3-4 weeks. Tumor volume and body weight would be measured twice weekly. At the end of the study, tumors would be excised, weighed, and analyzed for markers of translation and apoptosis by Western blotting (e.g., p-eIF4E, 4E-BP1, PARP).
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| ADME/Pharmacokinetics |
No pharmacokinetic data has been reported. As a small molecule with a molecular weight of 474.46 g/mol, eIF4A3-IN-5 has the potential for oral bioavailability. However, its specific ADME (absorption, distribution, metabolism, excretion) profile has not been published. Further studies are required to determine its half-life, clearance, and volume of distribution.
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| Toxicity/Toxicokinetics |
No specific toxicity data has been reported. As an inhibitor of a key translational factor, it is expected to have a narrow therapeutic window. Potential on-target toxicity may include effects on essential cellular processes in rapidly dividing normal tissues (e.g., bone marrow, gastrointestinal tract). For research use only.
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| References | |
| Additional Infomation |
eIF4A3-IN-5 is disclosed in patent US20170145026A1. It serves as a chemical probe to study the role of cap-dependent translation in cancer. The molecular formula is C26H22N2O7, and its precise IUPAC name is 2-(2-(3-cyanophenyl)-7-hydroxy-2-(4-methoxypyridin-2-yl)-2H-chromen-5-yl)acetic acid.
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| Molecular Formula |
C26H22N2O7
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|---|---|
| Exact Mass |
474.142
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| CAS # |
2100145-31-9
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| PubChem CID |
162641726
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
2.2
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
35
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| Complexity |
848
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| Defined Atom Stereocenter Count |
5
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| SMILES |
COC1=NC(=C2C(=C1)O[C@@]3([C@]2([C@@H]([C@@H]([C@H]3C4=CC=CC=C4)C(=O)O)O)O)C5=CC=C(C=C5)C#N)OC
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| InChi Key |
UADSEUZFIUVZDF-YHVMUTAASA-N
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| InChi Code |
InChI=1S/C26H22N2O7/c1-33-18-12-17-21(23(28-18)34-2)25(32)22(29)19(24(30)31)20(15-6-4-3-5-7-15)26(25,35-17)16-10-8-14(13-27)9-11-16/h3-12,19-20,22,29,32H,1-2H3,(H,30,31)/t19-,20-,22-,25+,26+/m1/s1
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| Chemical Name |
(2S,3R,4R,5S,6R)-6-(4-cyanophenyl)-2,3-dihydroxy-10,12-dimethoxy-5-phenyl-7-oxa-11-azatricyclo[6.4.0.02,6]dodeca-1(12),8,10-triene-4-carboxylic 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.) |
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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