1. Others
  2. Others

FR194738 free base 

Cat. No.: HY-100303
Handling Instructions

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.

FR194738 free base Chemical Structure

FR194738 free base Chemical Structure

CAS No. : 204067-45-8

Size Price Stock
1 mg USD 1690 Get quote
5 mg USD 2705 Get quote
10 mg USD 4328 Get quote

* Please select Quantity before adding items.

Other In-stock Forms of FR194738 free base:

Other Forms of FR194738 free base:

  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

FR194738 free base is a squalene epoxidase inhibitor. FR194738 inhibits squalene epoxidase activity in HepG2 cell homogenates with an IC50 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 [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].

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].

References
Cell Assay
[1]

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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[3]

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.

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

439.65

Formula

C₂₇H₃₇NO₂S

CAS No.

204067-45-8

SMILES

CC(OCC1=CSC=C1)(C)COC2=CC(CN(C/C=C/C#CC(C)(C)C)CC)=CC=C2

Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Shipping

Room temperature in continental US; may vary elsewhere

  • Molarity Calculator

  • Dilution Calculator

The molarity calculator equation

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass   Concentration   Volume   Molecular Weight *
= × ×

The dilution calculator equation

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
× = ×
C1   V1   C2   V2

Inquiry Online

Your information is safe with us. * Required Fields.

Product name

 

Salutation

Applicant name *

 

Email address *

Phone number *

 

Organization name *

Country or Region *

 

Requested quantity *

Remarks

Bulk Inquiry

Inquiry Information

Product Name:
FR194738 free base
Cat. No.:
HY-100303
Quantity:

FR194738 free base

Cat. No.: HY-100303