WAY-362450 (XL335) is a synthetic potent agonists of the farnesoid X receptor (FXR). WAY-362450 binds to the ligand-binding domain (LBD) of human FXR. WAY-362450 (XL335) also induced small heterodimer partner (SHP) expression and repressed cholesterol 7alpha-hydroxylase (CYP7A1) and sterol 12 alpha-hydroxylase (CYP8B1) expression. Oral administration of WAY-362450 to LDLR(-/-) mice results in lowering of cholesterol and triglycerides. Furthermore, treatment of wild type C57BL/6 mice with the FXR agonist WAY-362450, attenuated lipopolysaccharide-induced serum amyloid P component and serum amyloid A3 mRNA levels in the liver.
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||DMSO 30 mg/mL|
|Source||Biochem Biophys Res Commun (2014). Figure 1. WAY-362450|
|Cell Lines||Huh7 cells|
|Incubation Time||24 h|
|Results||No significant pathological changes were found and liver lipid staining is minimal in control liver specimens. Feeding 30% fructose for 8 weeks led to a nearly 6-fold increase of lipids contents in serum and liver respectively, and induced significant hepatic steatosis, characterized by the presence of macrovesicular and microvesicular lipid droplets in hepatocytes.|
Farnesoid X receptor agonist WAY-362450 attenuates liver inflammation and fibrosis in murine model of non-alcoholic steatohepatitis.
Zhang S, et al. J Hepatol. 2009 Aug;51(2):380-8. PMID: 19501927.
Activation of farnesoid X receptor prevents atherosclerotic lesion formation in LDLR-/- and apoE-/- mice.
Hartman HB, et al. J Lipid Res. 2009 Jun;50(6):1090-100. PMID: 19174369.
Discovery of XL335 (WAY-362450), a highly potent, selective, and orally active agonist of the farnesoid X receptor (FXR).
Flatt B, et al. J Med Chem. 2009 Feb 26;52(4):904-7. PMID: 19159286.
Suppression of interleukin-6-induced C-reactive protein expression by FXR agonists.
Zhang S, et al. Biochem Biophys Res Commun. 2009 Feb 6;379(2):476-9. PMID: 19118524.
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