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Purity: ≥98%
Turofexorate Isopropyl (also known as WAY-362450, Fxr 450 and XL335) is a novel, highly potent, selective and orally bioavailable FXR (farnesoid X receptor) agonist with EC50 of 4 nM, it is highly selective versus other nuclear receptors, such as LXR, PPAR, ER and etc. XL335 has shown to reduce IL-6-induced both mRNA and protein expression of CRP via FXR in human hepatoma Hep3B cells. XL335 remarkably reduced LPS-induced SAP and SAA3 mRNA expression in WT mice, but not in FXR/KO mice. It attenuates liver inflammation and fibrosis in murine model of non-alcoholic steatohepatitis.
| ln Vitro |
With an EC50 of 4 nM, turofexorate isopropyl (WAY-362450) is a strong, specific, and orally accessible FXR agonist. Turofexorate isopropyl (WAY-362450) exhibits a high degree of selectivity since, at doses up to 10 μM, no discernible cross-reactivity is seen with these receptors (LXRα, LXRβ, PPARα, PPARγ, PPARδ, RXRα, RARγ, VDR, SXR, ERα, ERβ, GR, AR, MR, and PR). In tests using FXR reporter genes and on FXR target genes in assays based on cells, WAY-362450 exhibits strong agonist action. Turofexorate isopropyl (WAY-362450), with an EC50 of 17, 230, and 33 nM, respectively, up-regulates the human bile salt excretory pump (BSEP), human small heterodimer partner (SHP), and mouse intestinal bile acid binding protein (IBABP) genes in promoter assays using reporter constructs. Furthermore, at 1 μM (13-, 2-, and 20-fold, respectively), WAY-362450 dramatically increases the expression of mRNAs encoding for BSEP, SHP, and IBABP in human cell cultures[1]. With an EC50 of 16 nM, turofexorate isopropyl (WAY-362450) potently stimulates reporter expression of luciferase. Turofexorate isopropyl (WAY-362450) is a strong inducer of endogenous FXR gene activation in primary human hepatocytes and mouse AML12 cells[2].
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| ln Vivo |
Turofexorate isopropyl (WAY-362450) also exhibits strong antiatherogenic activity in terms of a decrease in aortic arch lesions, as well as strong effects on lowering cholesterol and triglycerides in LDLR-/-mice. Triglycerides and cholesterol are reduced when Turofexorate isopropyl (WAY-362450) is given orally to LDLR-/-mice. In an atherosclerosis model, long-term treatment leads to a notable decrease in aortic arch lesions. When given to rats at a dose of 3 mg/kg (po and iv), turofexorate isopropyl (WAY-362450) exhibits good oral bioavailability (38%). Low clearance (3.3 L/kg, ~10% of hepatic blood flow), a long half-life of 25 hours, and a modest volume of distribution are present. There have been more pharmacokinetic studies conducted in mice and higher species; the results will be published elsewhere[1]. When rats are given 30 mg/kg of Turofexorate isopropyl (WAY-362450), their HDLc levels rise, but in hamsters, they fall, much like in mice [2]. When wild-type mice are given 30 mg/kg of Turofexorate isopropyl (WAY-362450), their SHP expression is induced, but not in FXR-/-mice. Turofexorate isopropyl (WAY-362450), in accordance with the established impacts of SHP induction on bile acid synthetic gene expression, significantly suppresses the expression of the CYP8B1 bile acid synthetic gene in wild-type mice but had no effect on CYP8B1 gene expression in FXR-/- mice[3].
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| 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.
[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. [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 |
| Molecular Formula |
C25H24F2N2O3
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| Molecular Weight |
438.47
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| CAS # |
629664-81-9
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| SMILES |
FC1=C(C([H])=C([H])C(=C1[H])C(N1C([H])=C(C(=O)OC([H])(C([H])([H])[H])C([H])([H])[H])C2=C(C3=C([H])C([H])=C([H])C([H])=C3N2[H])C(C([H])([H])[H])(C([H])([H])[H])C1([H])[H])=O)F
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| 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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| Preparing Stock Solutions | 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 |
*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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