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| Targets |
FR194738 HCl targets squalene epoxidase (SE), a key enzyme in the cholesterol biosynthesis pathway. Squalene epoxidase catalyzes the conversion of squalene to 2,3-oxidosqualene, a rate-limiting step in sterol biosynthesis. FR194738 HCl inhibits squalene epoxidase activity in HepG2 cell homogenates with an IC50 of 9.8 nM and in hamster liver microsomes with an IC50 of 14 nM. By inhibiting SE, FR194738 HCl blocks cholesterol biosynthesis at an early stage.
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| ln Vitro |
The incorporation of [14C]acetate into free cholesterol and cholesteryl ester is concentration-dependently inhibited in intact HepG2 cells by FR194738, with IC50 values of 4.9 and 8.0 nM, respectively. Intracellular buildup of [14C]squalene is induced by FR194738. An intermediary in the production of cholesterol, squalene, incorporates [14C]acetate more readily when FR194738 is present[1]. In HepG2 cell homogenate and liver microsomes from dogs and rats, FR194738 potently inhibits squalene epoxidase (SE). FR194738's ability to reduce cholesterol manufacture in HepG2 cells is compared to those of the HMG-CoA reductase inhibitors, Pravastatin, Fluvastatin, and Simvastatin. FR194738 has an IC50 of 2.1 nM, making it the most powerful of these drugs. The half-life of simvastatin is 40 nM, fluvastatin is 28 nM, and pravastatin is 5100 nM, respectively[2]. With an IC50 of 14 nM, FR194738 exhibits concentration-dependent inhibition of hamster liver microsomal squalene epoxidase activity[3].
In vitro, FR194738 HCl potently inhibits squalene epoxidase activity in HepG2 cell homogenates with an IC50 of 9.8 nM and in hamster liver microsomes with an IC50 of 14 nM. The compound inhibits the incorporation of [14C]acetate in intact HepG2 cells into free cholesterol with an IC50 of 4.9 nM. FR194738 HCl also inhibits cholesterol biosynthesis in HepG2 cells with an IC50 of 2.1 nM. These in vitro data demonstrate the compound's potent inhibition of cholesterol biosynthesis. |
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| ln Vivo |
After daily FR194738 and Pravastatin injection for 10 days, the serum cholesterol levels in the hamsters are measured. Serum levels of triglycerides, total, non-high density lipoprotein (HDL), and HDL cholesterol are all lowered with FR194738. When FR194738 is administered to hamsters, their HMG-CoA reductase activity is increased by 1.3 times at 32 mg/kg in comparison to the control group, but it does not change appreciably at 100 mg/kg[3].
In vivo, FR194738 HCl has been studied for its effects on cholesterol metabolism. As a potent squalene epoxidase inhibitor, the compound reduces cholesterol biosynthesis in vivo. FR194738 HCl has also been investigated for its antifungal properties, as squalene epoxidase is a target for antifungal agents. Detailed in vivo efficacy data are available in the scientific literature. The compound is for research purposes only and is not approved for clinical use. |
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| Enzyme Assay |
Enzyme activity assays for FR194738 HCl are performed using HepG2 cell homogenates or hamster liver microsomes as the enzyme source. Squalene epoxidase activity is measured by monitoring the conversion of radiolabeled squalene to 2,3-oxidosqualene. FR194738 HCl is incubated with the enzyme source and substrate at varying concentrations in appropriate assay buffer. The reaction is stopped, and product formation is quantified by radiometric detection or HPLC. IC50 values are calculated from concentration-response curves. Nonspecific activity is determined in control reactions without inhibitor.
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| ADME/Pharmacokinetics |
FR194738 HCl has a molecular weight of 505.0. The compound is a potent squalene epoxidase inhibitor with an IC50 of 9.8 nM in HepG2 cell homogenates and 14 nM in hamster liver microsomes. FR194738 HCl inhibits cholesterol biosynthesis in HepG2 cells with an IC50 of 2.1 nM. Detailed pharmacokinetic parameters are documented in the scientific literature. The compound is soluble in DMSO. It should be stored at -20degC.
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| Toxicity/Toxicokinetics |
Comprehensive toxicology data for FR194738 HCl are not extensively documented in publicly available sources. The compound is intended for research use only and is not approved for human therapeutic applications. Standard laboratory safety practices should be followed when handling this compound, including the use of appropriate personal protective equipment and adherence to institutional biosafety and chemical hygiene guidelines. The compound has a purity of ≥98%.
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| References |
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| Additional Infomation |
FR194738 HCl is a novel and potent small-molecule inhibitor of squalene epoxidase (SE), a key enzyme in cholesterol biosynthesis. It inhibits SE activity in HepG2 cell homogenates with an IC50 of 9.8 nM and inhibits cholesterol biosynthesis in HepG2 cells with an IC50 of 2.1 nM. FR194738 HCl has been studied for its potential applications in cholesterol metabolism research and as an antifungal agent. The compound is for research purposes only.
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| Molecular Formula |
C27H38CLNO2S
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| Molecular Weight |
476.114125728607
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| Exact Mass |
475.231
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| CAS # |
204067-52-7
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| Related CAS # |
FR194738 free base;204067-45-8
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| PubChem CID |
9869566
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| Appearance |
Typically exists as solid at room temperature
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
32
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| Complexity |
610
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl.S1C=CC(=C1)COC(C)(C)COC1=CC=CC(=C1)CN(C/C=C/C#CC(C)(C)C)CC
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| InChi Key |
XZCWZZDUAVANHV-VRTOBVRTSA-N
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| InChi Code |
InChI=1S/C27H37NO2S.ClH/c1-7-28(16-10-8-9-15-26(2,3)4)19-23-12-11-13-25(18-23)29-22-27(5,6)30-20-24-14-17-31-21-24;/h8,10-14,17-18,21H,7,16,19-20,22H2,1-6H3;1H/b10-8+;
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| Chemical Name |
(E)-N-ethyl-6,6-dimethyl-N-[[3-[2-methyl-2-(thiophen-3-ylmethoxy)propoxy]phenyl]methyl]hept-2-en-4-yn-1-amine;hydrochloride
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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: Please store this product in a sealed and protected environment, 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) |
DMSO : ~250 mg/mL (~525.09 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.37 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.37 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1004 mL | 10.5018 mL | 21.0035 mL | |
| 5 mM | 0.4201 mL | 2.1004 mL | 4.2007 mL | |
| 10 mM | 0.2100 mL | 1.0502 mL | 2.1004 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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