product name GW4064
Description: GW4064 is a selective agonist of farnesoid X receptor (FXR) with EC50 of 65 nM in CV1 cell line. It displays no activity at other nuclear receptors, including the retinoic acid receptor, at concentrations up to 1 μM. GW-4064 upregulates adipokine expression in preadipocytes and HepG2 cells. GW4064 could reduce induction of proinflammatory cytokines by LPS in vitro. GW4064 shows beneficial effects on cholesterol and TG (triglycerides) in various animal species. GW4064 is found to lower serum TG levels in both the KK-Ay and ob/ob mice potently. In KK-Ay mice, a 1-week administration of GW4064 also significantly lowers VLDL secretion. And in the SHP+/+ mice, GW4064 can also lower serum TGs.
References: Bioorg Med Chem Lett. 2008 Aug 1;18(15):4339-43; J Med Chem. 2000 Aug 10;43(16):2971-4.
542.84
Formula
C28H22Cl3NO4
CAS No.
278779-30-9
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 100 mg/mL (184.2 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
0.5% methylcellulose: 11 mg/mL
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19421413
| In Vitro |
In vitro activity: GW 4064 is a full agonist with EC50 values of 80 and 90 nM, respectively, in CV-1 cells transfected with mouse and human FXR expression vectors and an established reporter gene. There is no activity of GW 4064 on other nuclear receptors, including the retinoic acid receptor, at concentrations up to 1 μM. Thus, GW 4064 is a potent and selective nonsteroidal FXR agonist. Kinase Assay: Cell Assay: |
|---|---|
| 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. |
| Animal model | Fisher rats |
| Formulation & Dosage | Dissolved in 0.5% methyl cellulose; 0-100 mg/kg; Oral gavage |
| References | Bioorg Med Chem Lett. 2008 Aug 1;18(15):4339-43; J Med Chem. 2000 Aug 10;43(16):2971-4. |
