278779-30-9

Basic information

• Product Name: GW 4064
• Synonyms: GW 4064;3-[2-[2-Chloro-4-[[3-(2,6-Dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methoxy]phenyl]ethenyl]-benzoic Acid;Benzoic acid, 3-[2-[2-chloro-4-[[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methoxy]phenyl]ethenyl]-GW 4064;3-(2,6-Dichlorophenyl)-4-(3'-carboxy-2-chlorostilben-4-yl)oxymethyl-5-isopropylisoxazole;3-[2-[2-Chloro-4-[[3-(2,6-dichlorophenyl)-5-isopropylisoxazol-4-yl]Methoxy]phenyl]vinyl]benzoic acid;Benzoic acid, 3-[2-[2-chloro-4-[[3-(2,6-dichlorophenyl)-5-(1-Methylethyl)-4-isoxazolyl]Methoxy]phenyl]ethenyl]-;GW-4064,3-[2-[2-Chloro-4-[3-(2,6-dichlorophenyl)-5-isopropylisoxazol-4-ylMethoxy]phenyl]vinyl]benzoi;3-(2,6-Dichlorophenyl)-4-(3'-carboxy-2-chlorostilben-4-yl)oxymethyl-5-isopropylisoxazole GW 4064
• CAS NO: 278779-30-9
• Molecular Formula: C28H22Cl3NO4
• Molecular Weight: 542.84
• Product Categories: Intermediates & Fine Chemicals;Pharmaceuticals;Inhibitors
• Mol File: 278779-30-9.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 702.054 °C at 760 mmHg
• Flash Point: 378.389 °C
• Appearance: white/
• Density: 1.367 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.654
• Storage Temp.: Desiccate at +4°C
• Solubility: DMSO: soluble10mg/mL, clear
• PKA: 4.13±0.10(Predicted)
• CAS DataBase Reference: GW 4064(CAS DataBase Reference)
• NIST Chemistry Reference: GW 4064(278779-30-9)
• EPA Substance Registry System: GW 4064(278779-30-9)

Safety Data

• Hazard Codes: Xn
• Statements: 22-36
• Safety Statements: 26
• WGK Germany: 3
• Hazardous Substances Data: 278779-30-9(Hazardous Substances Data)

Usage

Description

GW 4064 is a synthetic isoxazole that functions as a novel nonsteroidal FXR nuclear receptor agonist and an estrogen receptor-related receptors (ERRs) agonist. It is utilized to explore the cellular and physiological roles of farnesoid X receptor (FXR), playing a significant role in various biological processes.

Uses

Used in Pharmaceutical Research:
GW 4064 is used as a research tool for investigating the functions and therapeutic potential of FXR and ERRs in cellular and physiological processes.
Used in Liver Protection Studies:
GW 4064 is used as a liver protectant to assess its ability to shield the livers of mice from lipopolysaccharide (LPS)-induced inflammation and apoptosis, offering insights into potential treatments for liver diseases.
Used in Intestinal Health Research:
In the field of intestinal health, GW 4064 is used as an agent to examine its capacity to inhibit mucosal injury in the ileum caused by lipopolysaccharide (LPS), contributing to a better understanding of inflammatory bowel diseases and their management.
Used in Tissue Treatment Applications:
GW 4064 is utilized in the treatment of ileal explants, providing a means to study its direct effects on tissue samples and furthering knowledge on its potential applications in medical treatments.

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.

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.

InChI:InChI=1/C28H22Cl3NO4/c1-16(2)27-21(26(32-36-27)25-22(29)7-4-8-23(25)30)15-35-20-12-11-18(24(31)14-20)10-9-17-5-3-6-19(13-17)28(33)34/h3-14,16H,15H2,1-2H3,(H,33,34)/b10-9+

Upstream product

• 933799-50-9 3-(2,6-dichlorophenyl)-4-(3'-carbomethoxy-2-chloro-stilben-4-yl)-oxymethyl-5-isopropyl-isoxazole 
• 25185-95-9 2,6-dichlorobenzaldoxime 
• 83-38-5 2,6-dichlorobenzaldehyde 
• 278597-30-1 [3-(2,6-dichlorophenyl)-5-(propan-2-yl)-1,2-oxazol-4-yl]methanol 
• 278597-28-7 methyl 3-(2,6-dichlorophenyl)-5-(propan-2-yl)-1,2-oxazole-4-carboxylate 
• 278597-32-3 3-(2,6-dichlorophenyl)-4-(3'-chloro-4'-formylphenoxy)-methyl-5-isopropyl-isoxazole 
• 278779-31-0 C₂₉H₂₄Cl₃NO₄ 

Downstream Products

• 1444198-09-7 (E)-3-(2-chloro-4-((3-(2,6-dichlorophenyl)-5-isopropylisoxazol-4-yl)methoxy) styryl)benzohydrazide 
• 1444198-06-4 (E)-2-methoxy-2-oxoethyl 3-(2-chloro-4-((3-(2,6-dichlorophenyl)-5-isopropylisoxazol-4-yl)methoxy)styryl)benzoate 

Relevant articles and documents

Substituted isoxazole analogs of farnesoid X receptor (FXR) agonist GW4064

Starting from the known FXR agonist GW 4064 1a, a series of alternately 3,5-substituted isoxazoles was prepared. Several of these analogs were potent full FXR agonists. A subset of this series, with a tether between the isoxazole ring and the 3-position aryl substituent, were equipotent FXR agonists to GW 4064 1a, with the 2,6-dimethyl phenol analog 1t having greater FRET FXR potency than GW 4064 1a.

Identification of a chemical tool for the orphan nuclear receptor FXR

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