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

Name: Turofexorate isopropyl
Brand: MedChemExpress
SKU: HY-50911
Rating: 5.0 (3 reviews)

Cat. No.: HY-50911 Purity: 99.76%: FAQs
Data Sheet SDS COA Handling Instructions

Molarity Calculator

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

For research use only. We do not sell to patients.

Turofexorate isopropyl Chemical Structure

CAS No. : 629664-81-9

Size	Price	Stock	Quantity

Free Sample (0.1 - 0.5 mg)		Apply Now
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	USD 72	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	USD 72	In-stock	Estimated Time of Arrival: December 31
Solid
5 mg	USD 65	In-stock	Estimated Time of Arrival: December 31
10 mg	USD 90	In-stock	Estimated Time of Arrival: December 31
25 mg	USD 180	In-stock	Estimated Time of Arrival: December 31
50 mg	USD 280	In-stock	Estimated Time of Arrival: December 31
100 mg	USD 420	In-stock	Estimated Time of Arrival: December 31
200 mg		Get quote
500 mg		Get quote

or Bulk Inquiry

* Please select Quantity before adding items.

This product is a controlled substance and not for sale in your territory.

Customer Review

Based on 3 publication(s) in Google Scholar

3 Publications Citing Use of MCE Turofexorate isopropyl

Featured Recommendations

•Related Screening Libraries:

•Related Small Molecules:

•Related Proteins:

Biological Activity
Protocol
Purity & Documentation
References
Customer Review

Description

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	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-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-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]
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]
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

Molecular Weight

438.47

Formula

C₂₅H₂₄F₂N₂O₃

CAS No.

629664-81-9

Appearance

Solid

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

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

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

Solvent & Solubility

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)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

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

View the 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.

Molarity Calculator
Dilution Calculator

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

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

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

In Vivo:

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.

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.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
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.
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.
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

mg/kg

Animal weight
(per animal)

Dosing volume
(per animal)

μL

Number of animals

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

Please enter your animal formula composition:

DMSO +

Tween-80 +

Saline

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

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).

Calculation results:

Working solution concentration: mg/mL

Method for preparing stock solution: mg drug dissolved in μL DMSO (Stock solution concentration: mg/mL).

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).

Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.

If the continuous dosing period exceeds half a month, please choose this protocol carefully.

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.

Purity & Documentation

Purity: 99.76%

Select Batch:

Data Sheet (286 KB) SDS (393 KB)

COA (256 KB) LCMS (275 KB)

Handling Instructions (2659 KB)

References

[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]

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

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

Help & FAQs

Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

Turofexorate isopropyl629664-81-9FXR-450 XL335 WAY-362450FXR450FXR 450XL335XL 335XL-335WAY362450WAY 362450WAY-362450FXRAutophagyNR1H4Inhibitorinhibitorinhibit

Please select a local distributor ナミキ商事株式会社コスモ・バイオ株式会社
Product Name			Salutation
Applicant Name *			Email Address *
Phone Number *			Organization Name *
Department *			Requested quantity *
Country or Region *
Remarks

Product Name			Lot #
Applicant Name *			Email Address *
Phone Number			Department *
Organization Name *			Country or Region *
Remarks

Name
Email *

	Sorry, but the email address you supplied was invalid.

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

Customer Review

Turofexorate isopropyl Related Antibodies

3 Publications Citing Use of MCE Turofexorate isopropyl

Featured Recommendations

•Related Screening Libraries:

•Related Small Molecules:

•Related Proteins:

Biological Activity

Protocol

Purity & Documentation

References

Customer Review

Turofexorate isopropyl Related Antibodies

Molarity Calculator

Dilution Calculator

Complete Stock Solution Preparation Table

Turofexorate isopropyl Related Classifications

Keywords:

Your Recently Viewed Products:

Customer Review

Request for HNMR Report

SAFETY DATA SHEET (SDS)

Request for HNMR Report