Turofexorate isopropyl
Based on 3 publication(s) in Google Scholar
Turofexorate isopropyl (FXR-450) is a potent, selective, and orally bioavailable FXR agonist with EC50 of 4 nM.
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- Pureté: 99.77%
- CAS No.: 629664-81-9
- Formule: C25H24F2N2O3
- Masse moléculaire:438.47
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Stockage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
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Activité biologique
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Chemical Information
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Solvant et solubilité
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- Pureté et documentation
- Références
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Publications Citing Use of MedChemExpress (MCE) Turofexorate isopropyl
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Activité biologique
EC50: 4 nM (FXR)[1]
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| CV-1 | EC50 |
17 nM
Compound: 6m XL-335, WAY-362450, FXR-450
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Agonist activity at FXR expressed in african green monkey CV1 cells coexpressed with human BSEP by reporter gene assay
Agonist activity at FXR expressed in african green monkey CV1 cells coexpressed with human BSEP by reporter gene assay
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[PMID: 19159286] |
| CV-1 | EC50 |
230 nM
Compound: 6m XL-335, WAY-362450, FXR-450
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Agonist activity at FXR expressed in african green monkey CV1 cells coexpressed with human SHP by reporter gene assay
Agonist activity at FXR expressed in african green monkey CV1 cells coexpressed with human SHP by reporter gene assay
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[PMID: 19159286] |
| CV-1 | EC50 |
33 nM
Compound: 6m XL-335, WAY-362450, FXR-450
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Agonist activity at FXR expressed in african green monkey CV1 cells coexpressed with mouse IBABP by reporter gene assay
Agonist activity at FXR expressed in african green monkey CV1 cells coexpressed with mouse IBABP by reporter gene assay
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[PMID: 19159286] |
| CV-1 | EC50 |
4 nM
Compound: 6m XL-335, WAY-362450, FXR-450
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Agonist activity at human FXR expressed in african green monkey CV1 cells co-expressing ECRE with RXR co-factor by luciferase reporter gene assay
Agonist activity at human FXR expressed in african green monkey CV1 cells co-expressing ECRE with RXR co-factor by luciferase reporter gene assay
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[PMID: 19159286] |
| CV-1 | IC50 |
10 μM
Compound: 6m XL-335, WAY-362450, FXR-450
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Antagonist activity at gal-AR expressed in african green monkey CV1 cells co-expressing MH100 with GRIP1 co-factor by luciferase reporter gene assay
Antagonist activity at gal-AR expressed in african green monkey CV1 cells co-expressing MH100 with GRIP1 co-factor by luciferase reporter gene assay
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[PMID: 19159286] |
| CV-1 | IC50 |
10 μM
Compound: 6m XL-335, WAY-362450, FXR-450
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Antagonist activity at gal-ERalpha expressed in african green monkey CV1 cells co-expressing MH100 by luciferase reporter gene assay
Antagonist activity at gal-ERalpha expressed in african green monkey CV1 cells co-expressing MH100 by luciferase reporter gene assay
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[PMID: 19159286] |
| CV-1 | IC50 |
10 μM
Compound: 6m XL-335, WAY-362450, FXR-450
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Antagonist activity at gal-GR expressed in african green monkey CV1 cells co-expressing MH100 by luciferase reporter gene assay
Antagonist activity at gal-GR expressed in african green monkey CV1 cells co-expressing MH100 by luciferase reporter gene assay
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[PMID: 19159286] |
| CV-1 | IC50 |
10 μM
Compound: 6m XL-335, WAY-362450, FXR-450
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Antagonist activity at gal-MR expressed in african green monkey CV1 cells co-expressing MH100 by luciferase reporter gene assay
Antagonist activity at gal-MR expressed in african green monkey CV1 cells co-expressing MH100 by luciferase reporter gene assay
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[PMID: 19159286] |
| CV-1 | IC50 |
10 μM
Compound: 6m XL-335, WAY-362450, FXR-450
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Antagonist activity at gal-PR expressed in african green monkey CV1 cells co-expressing MH100 by luciferase reporter gene assay
Antagonist activity at gal-PR expressed in african green monkey CV1 cells co-expressing MH100 by luciferase reporter gene assay
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[PMID: 19159286] |
| HEK293 | EC50 |
15 nM
Compound: 1, FXR-450
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Agonist activity at human FXR-LBD expressed in HEL293 cells by Gal4-luciferase assay
Agonist activity at human FXR-LBD expressed in HEL293 cells by Gal4-luciferase assay
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[PMID: 20095622] |
| HEK293 | EC50 |
152 nM
Compound: 1, FXR-450
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Agonist activity at mouse FXR-LBD expressed in HEL293 cells by Gal4-luciferase assay
Agonist activity at mouse FXR-LBD expressed in HEL293 cells by Gal4-luciferase assay
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[PMID: 20095622] |
| HEK293 | EC50 |
16 nM
Compound: 1, WAY-362450
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Agonist activity at gal4-tagged human FXR-ligand binding domain expressed in human HEK293 cells by luciferase reporter gene assay
Agonist activity at gal4-tagged human FXR-ligand binding domain expressed in human HEK293 cells by luciferase reporter gene assay
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[PMID: 19683924] |
Turofexorate isopropyl (WAY-362450) is a potent, selective, and orally bioavailable FXR agonist (EC50=4 nM). Turofexorate isopropyl (WAY-362450) is highly selective, as no significant cross-reactivity with these receptors (LXRα, LXRβ, PPARα, PPARγ, PPARδ, RXRα, RARγ, VDR, SXR, ERα, ERβ, GR, AR, MR, and PR) is observed at concentrations up to 10 μM. WAY-362450 displays potent agonist activity in the FXR reporter gene assays and on FXR target genes in cell-based assays. In promoter assays, utilizing reporter constructs under control of the human bile salt excretory pump (BSEP), human small heterodimer partner (SHP), and mouse intestinal bile acid binding protein (IBABP) genes are up-regulated by Turofexorate isopropyl (WAY-362450) with EC50 of 17, 230, and 33 nM, respectively. In addition, WAY-362450 significantly induces mRNAs encoding for BSEP, SHP, and IBABP in human cell cultures at 1 μM (13-, 2-, and 20-fold, respectively)[1]. Turofexorate isopropyl (WAY-362450) potently induces luciferase reporter expression with an EC50 of 16 nM. Turofexorate isopropyl (WAY-362450) is a potent stimulator of endogenous FXR gene activation in mouse AML12 cells and in primary human hepatocytes[2].
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.
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 629664-81-9
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Appearance Solid
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Masse moléculaire 438.47
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Formule C25H24F2N2O3
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Color Light yellow to yellow
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SMILES
O=C(C1=CN(C(C2=CC=C(F)C(F)=C2)=O)CC(C)(C)C3=C1NC4=C3C=CC=C4)OC(C)C
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Synonyms
FXR-450; XL335; WAY-362450
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Publications (3)
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Journal Impact Factor
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Most Recent
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J Biol Chem
PPARγ and C/EBPα enable adipocyte differentiation upon inhibition of histone methyltransferase PRC2 in malignant tumors. [Abstract]2024 Sep 12:107765. PMID: 39276936 -
Cell Cycle
2019 Aug;18(15):1784-1797. PMID: 31223053 -
Solvant et solubilité
DMSO : 25 mg/mL (57.02 mM; ultrasonic and warming and heat to 56°C; 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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
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 (5.70 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 (5.70 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 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.
Protocole
Mouse AML12 cells are plated at 200,000 cells/well on the 24-well plate in 1 mL of growth medium [DMEM/F12 10% FBS, 1% penicillin and streptomycin, 1% insulin-transferrin-selenium-G supplement (ITS), 0.1% Dexamethasone (40 ng/mL)/well. The cells are treated with increasing concentrations of Turofexorate isopropyl (WAY-362450) (0.001, 0.01, 0.1, 1 and 10 μM) or GW4064 for 24 h. Total RNA is prepared and analyzed by real-time RT-PCR, and short heterodimer partner (SHP) expression is normalized to GAPDH and reported as fold induction vs. vehicle-treated cells. Preplated 24-well plates of human male primary hepatocytes with matrigel overlay are obtained from Cellz Direct. Cells are maintained in serum-free Williams medium E and supplemented with penicillin/streptomycin, dexamethasone, ITS, L-glutamine, and HEPES buffer. They are treated overnight with vehicle (0.01% DMSO) or increasing concentrations of Turofexorate isopropyl (WAY-362450) or GW4064. Total RNA is purified using the Qiagen RNeasy clean kit, and gene expression is quantified by real-time RT-PCR with the Qiagen Quantitech kit using an ABI 7900. The relative amount of mRNA is normalized to 18S ribosomal RNA, and data shown represent an average of two independent experiments[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Mice[3]
Age- and sex-matched 8- to 12-week-old mice are fed standard chow and housed in temperature-controlled virus-free facility on a 12-h-light/dark cycle with free access to food and water. Where indicated, mice are fed either a Western diet containing 42% fat and 0.2% cholesterol by weight or this Western diet supplemented to contain 0.225 mg Turofexorate isopropyl (WAY-362450) per gram of diet. The mice consumed ~4 g diet per day, resulting in the delivery of ~30 mg of Turofexorate isopropyl (WAY-362450) per kg of body weight, assuming a 30 g body weight. Animals are maintained on these diets for 6 (apoE-/-) or 12 weeks (LDLR-/-). At the end of each study, animals are euthanized and blood samples collected via the orbital eye for lipid analysis. Liver and ileum tissue are removed for mRNA quantification, and aortas are removed and stored in 10% buffered formalin solution.
Rats[2]
Eight-week-old male Sprague Dawley rats and Syrian Golden hamsters are fed a 60% fructose/0.15% cholesterol diet. For the rat study, the rats are placed onto the diet for 2 wk and then treated by daily oral gavage with vehicle (80% polyethylene glycol/20% Tween) or varying concentrations of Turofexorate isopropyl (WAY-362450) (8/group) as indicated for 7 days (8 rats/group). The hamster study is conducted as a preventative treatment, so both the diet and drug treatments are initiated on day 1 and continued for 21 days (8 hamsters/group). On the last day after the final dose, the food is removed to allow a 3 h fast, and serum and liver are harvested for analysis as described above.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Pureté et documentation
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Fiche technique (286 KB)
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SDS (394 KB)
- English - EN (394 KB)
- Français - FR (394 KB)
- Deutsch - DE (394 KB)
- Norwegian - NO (394 KB)
- Español - ES (394 KB)
- Swedish - SV (394 KB)
- Italian - IT (394 KB)
- Korean - KR (394 KB)
- Portuguese - PT (394 KB)
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Instruction de manipulation (2659 KB)
Références
[1]. Flatt B, et al. Discovery of XL335 (WAY-362450), a highly potent, selective, and orally active agonist of the farnesoid X receptor (FXR). J Med Chem. 2009 Feb 26;52(4):904-7. [Content Brief]
[2]. Evans MJ, et al. A synthetic farnesoid X receptor (FXR) agonist promotes cholesterol lowering in models of dyslipidemia. Am J Physiol Gastrointest Liver Physiol. 2009 Mar;296(3):G543-52. [Content Brief]
[3]. Hartman HB, et al. Activation of farnesoid X receptor prevents atherosclerotic lesion formation in LDLR-/- and apoE-/- mice. J Lipid Res. 2009 Jun;50(6):1090-100. [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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.2807 mL | 11.4033 mL | 22.8066 mL | 57.0164 mL |
| 5 mM | 0.4561 mL | 2.2807 mL | 4.5613 mL | 11.4033 mL | |
| 10 mM | 0.2281 mL | 1.1403 mL | 2.2807 mL | 5.7016 mL | |
| 15 mM | 0.1520 mL | 0.7602 mL | 1.5204 mL | 3.8011 mL | |
| 20 mM | 0.1140 mL | 0.5702 mL | 1.1403 mL | 2.8508 mL | |
| 25 mM | 0.0912 mL | 0.4561 mL | 0.9123 mL | 2.2807 mL | |
| 30 mM | 0.0760 mL | 0.3801 mL | 0.7602 mL | 1.9005 mL | |
| 40 mM | 0.0570 mL | 0.2851 mL | 0.5702 mL | 1.4254 mL | |
| 50 mM | 0.0456 mL | 0.2281 mL | 0.4561 mL | 1.1403 mL |
Turofexorate isopropyl Related Classifications
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