FR194738 free base
Based on 2 publication(s) in Google Scholar
FR194738 free base is a squalene epoxidase inhibitor. FR194738 inhibits squalene epoxidase activity in HepG2 cell homogenates with an IC50 of 9.8 nM.
For research use only. We do not sell to patients.
- Purity: 99.84%
- CAS No.: 204067-45-8
- Formula: C27H37NO2S
- Molecular Weight:439.65
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Storage:Pure form -20°C, 3 years ; In solvent -80°C, 6 months , -20°C, 1 month
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocol
- Purity & Documentation
- References
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Help & FAQs
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Publications Citing Use of MedChemExpress (MCE) FR194738 free base
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Biological Activity
IC50: 9.8 nM (squalene epoxidase, in HepG2 cell homogenates)[1]
In intact HepG2 cells, FR194738 concentration-dependently inhibits the incorporation of [14C]acetate into free cholesterol and cholesteryl ester, with IC50s of 4.9 and 8.0 nM, respectively. FR194738 induces intracellular [14C]squalene accumulation. FR194738 increases the incorporation of [14C]acetate into squalene, an intermediate of cholesterol synthesis[1]. FR194738 potently inhibits squalene epoxidase (SE) in HepG2 cell homogenate and liver microsomes in dogs and rats. The inhibitory effect of FR194738 in comparison to the HMG-CoA reductase inhibitors, Simvastatin, Fluvastatin and Pravastatin, on cholesterol biosynthesis in HepG2 cells is examined. Among these compounds, FR194738 is the most potent, with an IC50 of 2.1 nM. The IC50s of Simvastatin, Fluvastatin and Pravastatin are 40, 28 and 5100 nM, respectively[2]. FR194738 inhibits hamster liver microsomal squalene epoxidase activity in a concentration-dependent manner with an IC50 of 14 nM[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Chemical Information
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CAS No. 204067-45-8
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Appearance Viscous Liquid
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Molecular Weight 439.65
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Formula C27H37NO2S
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Color Colorless to light yellow
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SMILES
CC(OCC1=CSC=C1)(C)COC2=CC(CN(C/C=C/C#CC(C)(C)C)CC)=CC=C2
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Pure form -20°C 3 years In solvent -80°C 6 months -20°C 1 month
Publications (2)
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Journal Impact Factor
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Most Recent
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Cancer Res
Squalene Epoxidase Metabolic Dependency Is a Targetable Vulnerability in Castration-Resistant Prostate Cancer. [Abstract]2022 Sep 2;82(17):3032-3044. PMID: 35767703 -
Clin Transl Med
Identifying squalene epoxidase as a metabolic vulnerability in high-risk osteosarcoma using an artificial intelligence-derived prognostic index. [Abstract]2024 Feb;14(2):e1586. PMID: 38372422
Solvent & Solubility
DMSO : 100 mg/mL (227.45 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (5.69 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: 2.5 mg/mL (5.69 mM); Suspended solution; Need ultrasonic
This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocol
HepG2 cells are grown in 225 cm2 culture flasks, and incubated for 18 h in medium A containing 10% human lipoprotein deficient serum and 1 μM L-654,969 to increase their squalene epoxidase activity. The HepG2 cells are washed and harvested by trypsin treatment. After centrifugation (1000×g, 5 min at 4°C), the supernatant fraction is removed by aspiration. The cell pellet is frozen and kept at -80 °C until use. On the day of the experiment, the stocked cell pellet is thawed, ruptured by sonication (5 s at 4°C) in 0.1 M Tris-HCl, pH 7.5 containing 1 mM EDTA, mixed with one-fourth volume of 2% Triton X-100, stood at 4°C for 30 min, and assayed for squalene epoxidase activity with some modifications. Aliquots of the mixture are incubated for 90 min at 37 °C with or without test compound (FR194738; 0.01 nM, 0.1 nM, 1 nM, 10 nM, 100 nM, 1 μM, and 10 μM) dissolved in DMSO (final 1%) in a final volume of 0.3 mL containing 0.1 M Tris-HCl, pH 7.5, 1 mM EDTA, 1 mM NADPH, 0.1 mM FAD, 0.3 mM AMO1618, an inhibitor of 2,3-oxidosqualene cyclase, 0.17% Triton X-100, and 8 μM [3H]squalene (3.7 kBq) dispersed in 0.075% Tween 80. The reaction is stopped by the addition of 0.3 mL of 10% ethanolic KOH. After incubation for 90 min at 75°C, non-saponifiable materials are extracted with 2 mL of petroleum ether. The extracts are evaporated under a nitrogen stream. The residue is taken up in a small volume of diethylether, spotted on a silica gel thin layer chromatography (TLC) plate and developed in benzene/ethyl acetate (99.5:0.5, v/v)[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Hamsters[3]
Six-week-old male golden Syrian hamsters (70-110 g) are used. Drugs are administered as a diet mixture for 10 d. Blood samples are collected via heart puncture under ether anesthesia and serum is prepared by centrifugation. The dose of 0.32% in diet corresponds to 127 and 116 mg/kg/d for FR194738 and Pravastatin, respectively, calculated from body weight and food intake.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Purity & Documentation
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Data Sheet (276 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Portuguese - PT (393 KB)
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Handling Instructions (2659 KB)
References
[1]. Sawada M, et al. Effect of FR194738, a potent inhibitor of squalene epoxidase, on cholesterol metabolism in HepG2 cells. Eur J Pharmacol. 2001 Nov 9;431(1):11-6. [Content Brief]
[2]. Sawada M, et al. Synthesis and biological activity of a novel squalene epoxidase inhibitor, FR194738. Bioorg Med Chem Lett. 2004 Feb 9;14(3):633-7. [Content Brief]
[3]. Sawada M, et al. Inhibition of cholesterol synthesis causes both hypercholesterolemia and hypocholesterolemia in hamsters. Biol Pharm Bull. 2002 Dec;25(12):1577-82. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.2745 mL | 11.3727 mL | 22.7454 mL | 56.8634 mL |
| 5 mM | 0.4549 mL | 2.2745 mL | 4.5491 mL | 11.3727 mL | |
| 10 mM | 0.2275 mL | 1.1373 mL | 2.2745 mL | 5.6863 mL | |
| 15 mM | 0.1516 mL | 0.7582 mL | 1.5164 mL | 3.7909 mL | |
| 20 mM | 0.1137 mL | 0.5686 mL | 1.1373 mL | 2.8432 mL | |
| 25 mM | 0.0910 mL | 0.4549 mL | 0.9098 mL | 2.2745 mL | |
| 30 mM | 0.0758 mL | 0.3791 mL | 0.7582 mL | 1.8954 mL | |
| 40 mM | 0.0569 mL | 0.2843 mL | 0.5686 mL | 1.4216 mL | |
| 50 mM | 0.0455 mL | 0.2275 mL | 0.4549 mL | 1.1373 mL | |
| 60 mM | 0.0379 mL | 0.1895 mL | 0.3791 mL | 0.9477 mL | |
| 80 mM | 0.0284 mL | 0.1422 mL | 0.2843 mL | 0.7108 mL | |
| 100 mM | 0.0227 mL | 0.1137 mL | 0.2275 mL | 0.5686 mL |
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