GW 4064

Uses

A novel nonsteroidal FXR nuclear receptor agonist.

Uses

GW4064 has been used:

• to investigate its ability to protect the livers of mice from lipopolysaccharide (LPS)-induced inflammation and apoptosis
• to examine its capability to inhibit mucosal injury in ileum caused by lipopolysaccharide (LPS)
• to treat ileal explants

Definition

ChEBI: GW 4064 is a stilbenoid.

General Description

GW4064 is a synthetic isoxazole, which is used to decipher the cellular and physiological functions of farnesoid X receptor (FXR). It is an estrogen receptor-related receptors (ERRs) agonist.

Biological Activity

Selective, non-steroidal farnesoid X receptor (FXR) agonist (EC 50 = 15 nM). Displays no activity at other nuclear receptors at concentrations up to 1 μ M. Improves hyperglycaemia and hyperlipidaemia in diabetic db/db mice.

Biochem/physiol Actions

GW4064 is a FXR agonist. GW4064 is a potent (EC50 = 15 nM), non-steroidal agonist of the orphan nuclear receptor FXR. It shows no activity on other nuclear receptors including RAR up to 1 mM. This is an important tool for the study of the involvment of FXR in a variety of biological activities.

storage

Store at +4°C

References

[1] chiang pc, thompson dc, ghosh s, heitmeier mr. a formulation-enabled preclinical efficacy assessment of a farnesoid x receptor agonist, gw4064, in hamsters and cynomolgus monkeys. j pharm sci. 2011 nov;100(11):4722-33.
[2] watanabe m, houten sm, wang l, moschetta a, mangelsdorf dj, heyman ra, moore dd, auwerx j. bile acids lower triglyceride levels via a pathway involving fxr, shp, and srebp-1c. j clin invest. 2004 may;113(10):1408-18.
[3] li w, fu j, cheng f, zheng m, zhang j, liu g, tang y. unbinding pathways of gw4064 from human farnesoid x receptor as revealed by molecular dynamics simulations. j chem inf model. 2012 nov 26;52(11):3043-52.