Details
Stereochemistry | ACHIRAL |
Molecular Formula | C28H22Cl3NO4 |
Molecular Weight | 542.838 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 1 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(C)C1=C(COC2=CC=C(\C=C\C3=CC(=CC=C3)C(O)=O)C(Cl)=C2)C(=NO1)C4=C(Cl)C=CC=C4Cl
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+
Molecular Formula | C28H22Cl3NO4 |
Molecular Weight | 542.838 |
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
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2047 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18621523 |
65.0 nM [EC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Preventing | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
PubMed
Title | Date | PubMed |
---|---|---|
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 |
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The farnesoid X receptor controls gene expression in a ligand- and promoter-selective fashion. | 2004 Mar 5 |
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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 |
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Protective effects of 6-ethyl chenodeoxycholic acid, a farnesoid X receptor ligand, in estrogen-induced cholestasis. | 2005 May |
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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 |
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VPAC1 expression is regulated by FXR agonists in the human gallbladder epithelium. | 2005 Sep |
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Chenodeoxycholic acid-mediated activation of the farnesoid X receptor negatively regulates hydroxysteroid sulfotransferase. | 2006 Aug |
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Bile acids induce adhesion molecule expression in endothelial cells through activation of reactive oxygen species, NF-kappaB, and p38. | 2006 Aug |
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A role for FXR and human FGF-19 in the repression of paraoxonase-1 gene expression by bile acids. | 2006 Feb |
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Downregulation of endothelin-1 by farnesoid X receptor in vascular endothelial cells. | 2006 Feb 3 |
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Regulation of the human bile acid UDP-glucuronosyltransferase 1A3 by the farnesoid X receptor and bile acids. | 2010 Apr |
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Genome-wide tissue-specific farnesoid X receptor binding in mouse liver and intestine. | 2010 Apr |
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Exposure to the synthetic FXR agonist GW4064 causes alterations in gene expression and sublethal hepatotoxicity in eleutheroembryo medaka (Oryzias latipes). | 2010 Feb 15 |
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Conformationally constrained farnesoid X receptor (FXR) agonists: heteroaryl replacements of the naphthalene. | 2011 Feb 15 |
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Tissue specific induction of p62/Sqstm1 by farnesoid X receptor. | 2012 |
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Modulation of farnesoid X receptor results in post-translational modification of poly (ADP-ribose) polymerase 1 in the liver. | 2013 Jan 15 |
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Human receptor activation by aroclor 1260, a polychlorinated biphenyl mixture. | 2014 Aug 1 |
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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 |
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Elevated copper impairs hepatic nuclear receptor function in Wilson's disease. | 2015 Sep |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23371517
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/10956205
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
Edited
Sat Dec 16 08:26:32 GMT 2023
by
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on
Sat Dec 16 08:26:32 GMT 2023
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Record UNII |
SR225WUZ0H
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Record Status |
Validated (UNII)
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Record Version |
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