[CAS NO. 204067-45-8] FR194738 free base
PRODUCTS SPECIFICATIONS [204067-45-8]
DESCRIPTION [204067-45-8]
Overview
| MDL | MFCD30533345 |
|---|---|
| Molecular Weight | 439.65 |
| Molecular Formula | C27H37NO2S |
| SMILES | CC(OCC1=CSC=C1)(C)COC2=CC(CN(C/C=C/C#CC(C)(C)C)CC)=CC=C2 |
Summary
FR194738 free base is a squalene epoxidase inhibitor. FR194738 inhibits squalene epoxidase activity in HepG2 cell homogenates with an IC 50 of 9.8 nM.
IC50 & Target
IC50: 9.8 nM (squalene epoxidase, in HepG2 cell homogenates) [1]
In Vitro
In intact HepG2 cells, FR194738 concentration-dependently inhibits the incorporation of [ 14 C]acetate into free cholesterol and cholesteryl ester, with IC 50 s of 4.9 and 8.0 nM, respectively. FR194738 induces intracellular [ 14 C]squalene accumulation. FR194738 increases the incorporation of [ 14 C]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 IC 50 of 2.1 nM. The IC 50 s 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 IC 50 of 14 nM [3] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
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] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Appearance
Viscous liquid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Pure form | -20°C | 3 years |
|---|---|---|
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 100 mg/mL ( 227.45 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 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 |
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.
- [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.
