Art. -Nr.: HY-50911

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Turofexorate isopropyl

(Synonyms: FXR-450; XL335; WAY-362450)

3 Cited Publications

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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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Reinheit: 99.77%
CAS. Nr.: 629664-81-9
Formel: C₂₅H₂₄F₂N₂O₃
Molecular Weight:438.47

Speicherung:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year

Turofexorate isopropyl Chemical Structure

CAS. Nr.: 629664-81-9

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Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
- Clinical Trial
Chemical Information
Publications (3)
Lösungsmittel & Löslichkeit
- In Vitro
- In Vivo
Protokoll
Reinheit & Dokumentation
Verweise
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

Turofexorate isopropyl (FXR-450) is a potent, selective, and orally bioavailable FXR agonist with EC₅₀ of 4 nM^[1].

IC₅₀ & Target

EC50: 4 nM (FXR)^[1]

Cellular Effect

Cell Line	Type	Value	Description	References
CV-1	EC₅₀	17 nM Compound: 6m XL-335, WAY-362450, FXR-450	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	[PMID: 19159286]
CV-1	EC₅₀	230 nM Compound: 6m XL-335, WAY-362450, FXR-450	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	[PMID: 19159286]
CV-1	EC₅₀	33 nM Compound: 6m XL-335, WAY-362450, FXR-450	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	[PMID: 19159286]
CV-1	EC₅₀	4 nM Compound: 6m XL-335, WAY-362450, FXR-450	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	[PMID: 19159286]
CV-1	IC₅₀	10 μM Compound: 6m XL-335, WAY-362450, FXR-450	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	[PMID: 19159286]
CV-1	IC₅₀	10 μM Compound: 6m XL-335, WAY-362450, FXR-450	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	[PMID: 19159286]
CV-1	IC₅₀	10 μM Compound: 6m XL-335, WAY-362450, FXR-450	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	[PMID: 19159286]
CV-1	IC₅₀	10 μM Compound: 6m XL-335, WAY-362450, FXR-450	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	[PMID: 19159286]
CV-1	IC₅₀	10 μM Compound: 6m XL-335, WAY-362450, FXR-450	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	[PMID: 19159286]
HEK293	EC₅₀	15 nM Compound: 1, FXR-450	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	[PMID: 20095622]
HEK293	EC₅₀	152 nM Compound: 1, FXR-450	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	[PMID: 20095622]
HEK293	EC₅₀	16 nM Compound: 1, WAY-362450	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	[PMID: 19683924]

In Vitro

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.

In Vivo

Turofexorate isopropyl (WAY-362450) also shows potent effects on cholesterol and triglyceride lowering in LDLR^-/- mice and antiatherogenic activity with respect to reduction of aortic arch lesions. Oral administration of Turofexorate isopropyl (WAY-362450) to LDLR^-/- mice results in lowering of cholesterol and triglycerides. Chronic administration in an atherosclerosis model results in significant reduction in aortic arch lesions. Turofexorate isopropyl (WAY-362450) is dosed in rat at 3 mg/kg (po and iv) and shows good oral bioavailability (38%). There is a protracted half-life of 25 h, modest volume of distribution, and low clearance (3.3 L/kg, ~10% of hepatic blood flow). Additional pharmacokinetic studies in mice and higher species have been completed, and the data will be reported elsewhere^[1]. In rats, Turofexorate isopropyl (WAY-362450) results in an elevation in HDLc levels, whereas in hamsters it causes a reduction similar to that observed in mice^[2] Treatment of wild-type mice with 30 mg/kg Turofexorate isopropyl (WAY-362450) results in induction of SHP expression in wild-type mice but not in FXR^-/- mice. Consistent with the known effects of SHP induction on bile acid synthetic gene expression, Turofexorate isopropyl (WAY-362450) strongly represses expression of the CYP8B1 bile acid synthetic gene in wild-type mice but had no effect on CYP8B1 gene expression in FXR^-/- mice^[3].

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

Clinical Trial

NCT Number	Sponsor	Condition	Start Date	Phase A549
NCT01329991	Plexxikon\|		2011-05	PHASE1

Chemical Information

CAS. Nr. 629664-81-9
Appearance Solid
Molecular Weight 438.47
Formel C₂₅H₂₄F₂N₂O₃
Color Light yellow to yellow
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
Synonyms

FXR-450; XL335; WAY-362450
Versand

Room temperature in continental US; may vary elsewhere.

Speicherung

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

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

Chronic activation of FXR-induced liver growth with tissue-specific targeting Cyclin D1. [Abstract]

2019 Aug;18(15):1784-1797. PMID: 31223053
Patent

US20200368199A1.

Lösungsmittel & Löslichkeit

In Vitro:

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)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

2.2807 mL

11.4033 mL

22.8066 mL

5 mM

0.4561 mL

2.2807 mL

4.5613 mL

10 mM

0.2281 mL

1.1403 mL

2.2807 mL

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.

Molaritätsrechner

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

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

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.

Protocol 1

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.

Protocol 2

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.

Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil

Solubility: ≥ 2.5 mg/mL (5.70 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
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

Protokoll

Cell Assay^[2]

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.

Animal Administration^[3]^[2]

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.

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (286 KB)
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)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

Verweise

[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]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

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

Keywords

Turofexorate isopropyl

3 Cited Publications

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Turofexorate isopropyl

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Publications Citing Use of MedChemExpress (MCE) Turofexorate isopropyl

Biologische Aktivität

Chemical Information

Publications (3)

Lösungsmittel & Löslichkeit

Protokoll

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

Turofexorate isopropyl

Metabolism/Protease Compound Library

Anti-Cancer Compound Library

Clinical Compound Library

Autophagy Compound Library

Orally Active Compound Library

Targeted Diversity Library

Human Metabolite Library

Nuclear Receptor Compound Library

Metabolic Enzyme Compound Library

Highly Selective Activators Library

Cell Death Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

Clinical Compound Library Plus

Bioactive Compound Library

Non-Alcoholic Fatty Liver Disease (NAFLD) Compound Library

High-Throughput Bioactive Compound Library

Mass Spectrometry Human Metabolite Library

Publications Citing Use of MedChemExpress (MCE) Turofexorate isopropyl

Biologische Aktivität

Chemical Information

Publications (3)

Lösungsmittel & Löslichkeit

Protokoll

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

Turofexorate isopropyl Related Classifications

HY-50911 Related Classifications