FR194738 free base |
| Catalog No.GC31434 |
FR194738 base libre est un inhibiteur de la squalène époxydase.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 204067-45-8
Sample solution is provided at 25 µL, 10mM.
;)
_1-7.$$$37316672@70.jpg');)
;)
;)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
;)
;)
;)
_1124-1138.$$$35908550@30.jpg');)
_766-780.$$$37100057@30.jpg');)
_418-432.$$$36893736@30.jpg');)
_240-255.$$$35108512@29.jpg');)
_533-545.$$$36543525@28.jpg');)
_264-276.$$$36600053@22.jpg');)
_2214998.$$$@0.jpg');)
FR194738 free base is a squalene epoxidase inhibitor. FR194738 inhibits squalene epoxidase activity in HepG2 cell homogenates with an IC50 of 9.8 nM.
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].
Serum lipid levels in hamsters after daily administration of FR194738 and Pravastatin for 10 d are measured. FR194738 reduces the serum levels of total, non high density lipoprotein (HDL) and HDL cholesterol, and triglyceride. Treatment of hamsters with FR194738 increases HMG-CoA reductase activity by 1.3-fold at 32 mg/kg compared to the control group and does not significantly change that at 100 mg/kg[3].
[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. [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. [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.
Cell experiment: | 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]. |
Animal experiment: | 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. |
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. | |
| Cas No. | 204067-45-8 | SDF | |
| Canonical SMILES | CC(OCC1=CSC=C1)(C)COC2=CC(CN(C/C=C/C#CC(C)(C)C)CC)=CC=C2 | ||
| Formula | C27H37NO2S | M.Wt | 439.65 |
| Solubility | Soluble in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.2745 mL | 11.3727 mL | 22.7454 mL |
| 5 mM | 0.4549 mL | 2.2745 mL | 4.5491 mL |
| 10 mM | 0.2275 mL | 1.1373 mL | 2.2745 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 24 reference(s) in Google Scholar.)
GLPBIO products are for RESEARCH USE ONLY. Please make sure your review or question is research based.
Required fields are marked with *