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Details

Stereochemistry ACHIRAL
Molecular Formula C28H22Cl3NO4
Molecular Weight 542.8384
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of GW-4064

SMILES

CC(C)c1c(COc2ccc(/C(/[H])=C(\[H])/c3cccc(c3)C(=O)O)c(c2)Cl)c(-c4c(cccc4Cl)Cl)no1

InChI

InChIKey=BYTNEISLBIENSA-MDZDMXLPSA-N
InChI=1S/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+

HIDE SMILES / InChI

Molecular Formula C28H22Cl3NO4
Molecular Weight 542.8384
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

GW-4064 is a synthetic small molecule selective agonist of the orphan nuclear receptor FXR developed by GlaxoSmithKline. GW-4064-mediated FXR activation ameliorates diet-induced obesity, suppresses hepatic lipid accumulation, and maintains glucose and lipid homeostasis in C57BL/6 mice. GW-4064-treated tumors exhibited decreased levels of leptin-regulated proteins along with a strong staining intensity for SOCS3. Thus, FXR ligand GW-4064 might represent an emerging potential anti-cancer therapy able to block the tumor supportive role of activated fibroblasts within the breast microenvironment.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
65.0 nM [EC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Preventing
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Identification of a chemical tool for the orphan nuclear receptor FXR.
2000 Aug 10
Hepatoprotection by the farnesoid X receptor agonist GW4064 in rat models of intra- and extrahepatic cholestasis.
2003 Dec
Farnesoid X receptor activates transcription of the phospholipid pump MDR3.
2003 Dec 19
Guggulsterone is a farnesoid X receptor antagonist in coactivator association assays but acts to enhance transcription of bile salt export pump.
2003 Mar 21
Retinoid X receptor (RXR) agonist-induced antagonism of farnesoid X receptor (FXR) activity due to absence of coactivator recruitment and decreased DNA binding.
2003 Mar 21
Polyunsaturated fatty acids are FXR ligands and differentially regulate expression of FXR targets.
2004 Aug
The farnesoid X receptor controls gene expression in a ligand- and promoter-selective fashion.
2004 Mar 5
The methyl transferase PRMT1 functions as co-activator of farnesoid X receptor (FXR)/9-cis retinoid X receptor and regulates transcription of FXR responsive genes.
2005 Aug
Protective effects of 6-ethyl chenodeoxycholic acid, a farnesoid X receptor ligand, in estrogen-induced cholestasis.
2005 May
Cross-talk between farnesoid-X-receptor (FXR) and peroxisome proliferator-activated receptor gamma contributes to the antifibrotic activity of FXR ligands in rodent models of liver cirrhosis.
2005 Oct
VPAC1 expression is regulated by FXR agonists in the human gallbladder epithelium.
2005 Sep
Chenodeoxycholic acid-mediated activation of the farnesoid X receptor negatively regulates hydroxysteroid sulfotransferase.
2006 Aug
Bile acids induce adhesion molecule expression in endothelial cells through activation of reactive oxygen species, NF-kappaB, and p38.
2006 Aug
A role for FXR and human FGF-19 in the repression of paraoxonase-1 gene expression by bile acids.
2006 Feb
Downregulation of endothelin-1 by farnesoid X receptor in vascular endothelial cells.
2006 Feb 3
The farnesoid X receptor FXRalpha/NR1H4 acquired ligand specificity for bile salts late in vertebrate evolution.
2007 Sep
Differentiated CaCo-2 cells as an in-vitro model to evaluate de-novo apolipoprotein A-I production in the small intestine.
2009 Jun
Hematopoietically expressed homeobox is a target gene of farnesoid X receptor in chenodeoxycholic acid-induced liver hypertrophy.
2009 Mar
Regulation of the human bile acid UDP-glucuronosyltransferase 1A3 by the farnesoid X receptor and bile acids.
2010 Apr
Genome-wide tissue-specific farnesoid X receptor binding in mouse liver and intestine.
2010 Apr
Exposure to the synthetic FXR agonist GW4064 causes alterations in gene expression and sublethal hepatotoxicity in eleutheroembryo medaka (Oryzias latipes).
2010 Feb 15
Two farnesoid X receptor alpha isoforms in Japanese medaka (Oryzias latipes) are differentially activated in vitro.
2010 Jul 1
Lithocholic acid disrupts phospholipid and sphingolipid homeostasis leading to cholestasis in mice.
2011 Apr
Farnesoid X receptor activation inhibits inflammation and preserves the intestinal barrier in inflammatory bowel disease.
2011 Apr
Tissue specific induction of p62/Sqstm1 by farnesoid X receptor.
2012
Farnesoid X receptor induces murine scavenger receptor Class B type I via intron binding.
2012
A tea catechin, epigallocatechin-3-gallate, is a unique modulator of the farnesoid X receptor.
2012 Jan 15
Involvement of multiple elements in FXR-mediated transcriptional activation of FGF19.
2012 Oct
Mechanism of tissue-specific farnesoid X receptor in suppressing the expression of genes in bile-acid synthesis in mice.
2012 Sep
Intrahepatic cholestasis of pregnancy levels of sulfated progesterone metabolites inhibit farnesoid X receptor resulting in a cholestatic phenotype.
2013 Feb
Modulation of farnesoid X receptor results in post-translational modification of poly (ADP-ribose) polymerase 1 in the liver.
2013 Jan 15
Human receptor activation by aroclor 1260, a polychlorinated biphenyl mixture.
2014 Aug 1
Dysregulation of retinoic acid receptor diminishes hepatocyte permissiveness to hepatitis B virus infection through modulation of sodium taurocholate cotransporting polypeptide (NTCP) expression.
2015 Feb 27
Elevated copper impairs hepatic nuclear receptor function in Wilson's disease.
2015 Sep
Patents

Patents

Sample Use Guides

Mice: Fifteen week-old C57BL/6 mice fed with high-fat diet (HFD) or high-fat, high-cholesterol diet were treated by twice weekly injection of GW-4064 (50 mg/kg) intraperitoneally or DMSO (carrier solution) for 6 weeks. Activation of FXR by GW-4064 suppressed weight gain in C57BL/6 mice fed with either HFD or high-fat and high-cholesterol diet.
Route of Administration: Intraperitoneal
In Vitro Use Guide
Curator's Comment:: GW-4064 (5 umol/L; 24 h), a specific FXR agonist, induced nuclear translocation of the receptor in T84 cells and attenuated Cl(-) secretory responses to both Ca(2+) and cAMP-dependent agonists. GW-4064 also prevented agonist-induced inhibition of NHE3 in Caco-2 cells. https://www.ncbi.nlm.nih.gov/pubmed/23916961
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 uM.
Substance Class Chemical
Created
by admin
on Sat Jun 26 15:15:26 UTC 2021
Edited
by admin
on Sat Jun 26 15:15:26 UTC 2021
Record UNII
SR225WUZ0H
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
GW-4064
Common Name English
GW-4064X
Code English
BENZOIC ACID, 3-(2-(2-CHLORO-4-((3-(2,6-DICHLOROPHENYL)-5-(1-METHYLETHYL)-4-ISOXAZOLYL)METHOXY)PHENYL)ETHENYL)-
Systematic Name English
Code System Code Type Description
CAS
292047-56-4
Created by admin on Sat Jun 26 15:15:26 UTC 2021 , Edited by admin on Sat Jun 26 15:15:26 UTC 2021
SUPERSEDED
FDA UNII
SR225WUZ0H
Created by admin on Sat Jun 26 15:15:26 UTC 2021 , Edited by admin on Sat Jun 26 15:15:26 UTC 2021
PRIMARY
PUBCHEM
9893571
Created by admin on Sat Jun 26 15:15:26 UTC 2021 , Edited by admin on Sat Jun 26 15:15:26 UTC 2021
PRIMARY
EPA CompTox
278779-30-9
Created by admin on Sat Jun 26 15:15:26 UTC 2021 , Edited by admin on Sat Jun 26 15:15:26 UTC 2021
PRIMARY
CAS
278779-30-9
Created by admin on Sat Jun 26 15:15:26 UTC 2021 , Edited by admin on Sat Jun 26 15:15:26 UTC 2021
PRIMARY
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