![1,3-Bis[3,5-bis(trifluoromethyl)phenyl]urea](/upload/0319/V111252.png)
| Size | Price | Stock | Qty |
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| 100mg |
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| 250mg |
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| 500mg |
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| 1g |
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| Other Sizes |
| Targets |
1,3-Bis[3,5-bis(trifluoromethyl)phenyl]urea targets the heme-regulated inhibitor (HRI), an eIF2alpha kinase. By activating HRI, the compound promotes phosphorylation of eIF2alpha (eukaryotic initiation factor 2 alpha), which leads to reduced formation of the eIF2·GTP·tRNAiMet ternary complex and global inhibition of protein synthesis. This mechanism can induce integrated stress response (ISR) and has been shown to inhibit cancer cell proliferation. The compound's structure is highly fluorinated, which enhances lipophilicity and metabolic stability.
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| ln Vitro |
In vitro, 1,3-Bis[3,5-bis(trifluoromethyl)phenyl]urea is a potent activator of the eIF2alpha kinase HRI. By activating HRI, it promotes eIF2alpha phosphorylation, reduces the eIF2·GTP·tRNAiMet ternary complex, and inhibits protein synthesis. The compound inhibits the proliferation of various cancer cell lines. Specific IC₅0 values against cancer cells were not reported in the search results, but the mechanism is well-characterized. The compound's potent activity is attributed to the strong electron-withdrawing effect of the trifluoromethyl groups.
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| ln Vivo |
In vivo, 1,3-Bis[3,5-bis(trifluoromethyl)phenyl]urea has potential as an anticancer agent by activating the integrated stress response (ISR) and inhibiting protein synthesis. As an eIF2alpha kinase activator, it may induce apoptosis in cancer cells while sparing normal cells. Specific in vivo efficacy data (e.g., xenograft studies) was not detailed in the search results, but the compound is described as inhibiting cancer cell proliferation, indicating potential utility in oncology research.
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| Enzyme Assay |
In vitro eIF2alpha phosphorylation (Western blotting): Cancer cells (e.g., HeLa, MCF-7, or HCT116) are seeded in 6-well plates (3×10⁵ cells/well) and incubated overnight. 1,3-Bis[3,5-bis(trifluoromethyl)phenyl]urea is dissolved in DMSO and added to cells at concentrations of 0.1-100 microM for 4-24 h. Cells are lysed in RIPA buffer with protease and phosphatase inhibitors. Western blotting is performed using anti-phospho-eIF2alpha (Ser51) and anti-total eIF2alpha antibodies. The ratio of p-eIF2alpha/total eIF2alpha is quantified by densitometry. Positive control: thapsigargin (1 microM) or tunicamycin (2 microg/mL), classic ER stress inducers that activate eIF2alpha kinases.
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| Cell Assay |
Cellular proliferation and apoptosis assay: Cancer cells (e.g., HeLa, MCF-7, HCT116) are seeded in 96-well plates (5,000-10,000 cells/well) in DMEM with 10% FBS and incubated overnight. 1,3-Bis[3,5-bis(trifluoromethyl)phenyl]urea is serially diluted (0.01-100 microM) and added to cells for 48-72 h. Cell viability is measured by MTT or CellTiter-Glo. IC₅0 is calculated. Apoptosis is confirmed by Annexin V-FITC/PI flow cytometry and caspase-3/7 activity. Protein synthesis inhibition can be assessed by [3⁵S]-methionine/cysteine metabolic labeling or by a non-radioactive puromycin incorporation assay (SUnSET, surface sensing of translation).
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| Animal Protocol |
In vivo xenograft model (not specific to this compound but typical for eIF2alpha pathway modulators): Female BALB/c nude mice (6-8 wk) are subcutaneously inoculated with 5×10⁶ cancer cells (e.g., HeLa or HCT116) in 0.1 mL PBS/Matrigel (1:1). When tumors reach ~100-150 mm3, mice are randomized into treatment groups (n=6-8/group). 1,3-Bis[3,5-bis(trifluoromethyl)phenyl]urea is formulated in 5% DMSO + 40% PEG300 + 55% saline or in a lipid-based vehicle, administered intraperitoneally or orally at 10-50 mg/kg once daily or every other day for 2-3 weeks. Tumor volume is measured every 3 days with calipers. Tumors are harvested for Western blotting to measure p-eIF2alpha and downstream targets (ATF4, CHOP). This protocol would apply if in vivo studies were conducted.
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| ADME/Pharmacokinetics |
No specific PK data for 1,3-Bis[3,5-bis(trifluoromethyl)phenyl]urea is available. As a highly fluorinated, lipophilic compound (MW 484.24, Log P >5), it has poor aqueous solubility and may require formulation in organic solvents (DMSO, PEG300) or lipid-based vehicles for administration. Oral absorption is likely low; intraperitoneal or intravenous administration would be preferred for in vivo studies. The trifluoromethyl groups confer metabolic stability by blocking CYP450-mediated oxidation, leading to a potentially longer half-life (t½ > 6-12 h). Distribution to adipose tissue and liver is expected. Metabolism may be minimal; excretion likely via bile.
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| Toxicity/Toxicokinetics |
No specific toxicology data for 1,3-Bis[3,5-bis(trifluoromethyl)phenyl]urea is available. The compound's mechanism (eIF2alpha phosphorylation and protein synthesis inhibition) could affect normal tissues with high protein turnover (e.g., gastrointestinal tract, bone marrow). However, cancer cells may be more sensitive due to higher baseline ER stress. Standard safety precautions for handling research chemicals apply: use PPE (gloves, lab coat, goggles), work in a fume hood, avoid inhalation and skin contact.
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| References | |
| Additional Infomation |
1,3-Bis[3,5-bis(trifluoromethyl)phenyl]urea (CAS# 3824-74-6) is a research-grade compound that activates the eIF2alpha kinase HRI, leading to phosphorylation of eIF2alpha, inhibition of protein synthesis, and suppression of cancer cell proliferation. It is not an FDA-approved drug. The compound is a tool for studying the integrated stress response (ISR), translational control, and cancer biology. For research use only, not for diagnostic or therapeutic applications.
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| Molecular Formula |
C17H8F12N2O
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| Molecular Weight |
484.24
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| Exact Mass |
484.045
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| CAS # |
3824-74-6
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| PubChem CID |
478241
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| Appearance |
Solid powder
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| Hydrogen Bond Donor Count |
2
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
32
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| Complexity |
556
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=C(C=C(C=C1C(F)(F)F)NC(=O)NC2=CC(=CC(=C2)C(F)(F)F)C(F)(F)F)C(F)(F)F
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| InChi Key |
YGCOMBKZFUMALE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H8F12N2O/c18-14(19,20)7-1-8(15(21,22)23)4-11(3-7)30-13(32)31-12-5-9(16(24,25)26)2-10(6-12)17(27,28)29/h1-6H,(H2,30,31,32)
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| Chemical Name |
1,3-bis[3,5-bis(trifluoromethyl)phenyl]urea
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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 Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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 | 2.0651 mL | 10.3255 mL | 20.6509 mL | |
| 5 mM | 0.4130 mL | 2.0651 mL | 4.1302 mL | |
| 10 mM | 0.2065 mL | 1.0325 mL | 2.0651 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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