GW4064 is a FXR agonist. There is no activity of GW4064 at other nuclear receptors at concentrations up to 1 μM. Treatment of differentiated 3T3-L1 adipocytes with the FXR-specific synthetic agonist GW4064 enhanced insulin signaling and insulin-stimulated glucose uptake. Finally, treatment with GW4064 improved insulin resistance in genetically obese ob/ob mice in vivo. Pharmacokinetic analysis in rats shows that GW 4064 possesses an oral bioavailability of 10% with a t1/2 = 3.5 h. Fisher rats are dosed with GW 4064 by oral gavage. After 7 days, a dose-dependent lowering of serum triglycerides is observed in the rats receiving GW 4064, with an ED50 = 20 mg/kg.
|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 100 mg/mL|
|Source||World J Gastroenterol (2014). Figure 1. GW4064|
|Incubation Time||7 d|
|Results||Treatment with the FXR agonist GW4064 also significantly decreased serum ALT and AST levels in HF diet-fed mice treated with LPS, further suggesting that FXR may have a protective role against liver injury in this NAFLD model|
Bile acid receptor agonist GW4064 regulates PPARγ coactivator-1α expression through estrogen receptor-related receptor α.
Dwivedi SK, et al. Mol Endocrinol. 2011 Jun;25(6):922-32. PMID: 21493670.
The farnesoid X receptor modulates adiposity and peripheral insulin sensitivity in mice.
Cariou B, et al. J Biol Chem. 2006 Apr 21;281(16):11039-49. PMID: 16446356.
Hepatoprotection by the farnesoid X receptor agonist GW4064 in rat models of intra- and extrahepatic cholestasis.
Liu Y, et al. J Clin Invest. 2003 Dec;112(11):1678-87. PMID: 14623915.
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