Turofexorate Isopropyl (XL335)

Catalog No.S2694 Batch:S269401

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Technical Data

Formula

C25H24F2N2O3
Molecular Weight 438.47 CAS No. 629664-81-9
Solubility (25°C)* In vitro DMSO 33 mg/mL (75.26 mM)
Ethanol 2 mg/mL (4.56 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description Turofexorate Isopropyl (XL335, Fxr 450) is a potent, selective FXR agonist with EC50 of 4 nM, highly selective versus other nuclear receptors, such as LXR, PPAR, ER and etc. Phase 1.
Targets
FXR [1]
4 nM(EC50)
In vitro WAY-362450 binds to the ligand-binding domain (LBD) of human FXR. WAY-362450 resides in a predominately hydrophobic pocket with only a few polar atoms making contact with WAY-362450. WAY-362450 promotes transcription of the human BSEP, human SHP, and mouse IBABP genes utilizing reporter constructs with EC50 of 17, 230, and 33 nM, respectively in promoter assays. WAY-362450 at concentration of 1 μM significantly induces mRNAs encoding for BSEP, SHP, and IBABP in human cell cultures to 13-, 2-, and 20-fold, respectively. [1] WAY-362450 at concentration of 1 μM suppresses interleukin-6-induced CRP expression in human Hep3B hepatoma cells, and the inhibitory effect is attenuated when knockdown of FXR by short interfering RNA.
In vivo WAY-362450 administrated intravenously or orally at does of 3 mg/kg in rats with a protracted half-life of 25 h, modest volume of distribution, and low clearance of 3.3 L/kg. WAY-362450 administered orally at dose of 10 mg/kg in normal C57bl/6 mice for a period of 7 days significantly lowers triglycerides to 62.0 ± 6.4 mg/dL and total cholesterol to 78.1 ± 5.0 mg/dL. WAY-362450 administered orally at dose of 1 and 3 mg/kg daily for 6 weeks in LDLR−/− mice, triglycerides is lowered by 19% and 39%, respectively, total cholesterol is lowered by 23% and 50%, respectively and lesion formation by 18% and 36%, respectively. [1] WAY-362450 intraperitoneally administrated at dose of 30 mg/kg daily for 4 days in wild type C57BL/6 mice attenuates lipopolysaccharide-induced serum amyloid P component and serum amyloid A3 mRNA levels in the liver. [3] WAY-362450 orally administered at dose of 30 mg/kg/day for 4 weeks in adult male C57BL/6 mice reduces inflammatory cell infiltration and hepatic fibrosis, the reduction in inflammatory cell infiltration correlates with deceased serum levels of keratinocyte derived chemokine (mKC) and MCP 1 and decreased hepatic gene expression of MCP-1 and VCAM-1, and the reduction of hepatic fibrosis by WAY-362450 treatment corresponded to a reduction in hepatic gene expression of fibrosis markers. [3] WAY-362450 administrated orally at dose of 30mg/kg in LDLR−/− and apoE−/− mice blocks diet-induced hypertriglyceridemia and elevations of non-HDL cholesterol and produced a near complete inhibition of aortic lesion formation, WAY-362450 also induced small heterodimer partner (SHP) expression and repressed cholesterol 7α-hydroxylase (CYP7A1) and sterol 12 α-hydroxylase (CYP8B1) expression. [4]

Protocol (from reference)

Animal Study:[1]
  • Animal Models

    Seven week old male C57bl/6 mice

  • Dosages

    10 mg/kg

  • Administration

    Administrated orally once daily in the morning for a period of 7 days

Customer Product Validation

, , Oncotarget, 2015, 6(6):4226-38.

Selleck's Turofexorate Isopropyl (XL335) has been cited by 4 publications

Chronic activation of FXR-induced liver growth with tissue-specific targeting Cyclin D1. [ Cell Cycle, 2019, 18(15):1784-1797] PubMed: 31223053
Farnesoid X receptor associates with β-catenin and inhibits its activity in hepatocellular carcinoma [Liu X, et al. Oncotarget, 2015, 6(6):4226-38] PubMed: 25650661
Agonist of farnesoid X receptor protects against bile acid induced damage and oxidative stress in mouse placenta--a study on maternal cholestasis model. [ Placenta, 2015, 36(5):545-51] PubMed: 25747729
Activation of farnesoid X receptor induces RECK expression in mouse liver. [ Biochem Biophys Res Commun, 2014, 443(1):211-6] PubMed: 24291500

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.