GW4064 |
Catalog No.GC10975
One-Click Copy Product Info
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GW4064, as a synthetic FXR agonist with an EC50 of 65nM, is used for the treatment of cholestatic liver diseases, metabolic syndrome and alcoholic liver disease.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 278779-30-9
Sample solution is provided at 25 µL, 10mM.
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GW4064, as a synthetic FXR agonist with an EC50 of 65nM, is used for the treatment of cholestatic liver diseases, metabolic syndrome and alcoholic liver disease[1].
In vitro, the IC50 values of GW4064 on SW620 and HT-29 cells were 7.6μM and 13.8μM, respectively[2]. GW4064 dose dependently enhanced the basal cAMP level with an EC50 of 0.241μM, and suppressed forskolin-induced cAMP accumulation with IC50 of 0.07μM on HEK cells[3].
In vivo, treatment of short bowel syndrome (SBS) rat model with GW4064 (30mg/kg every other day; 2wk; i.p.). GW4064 rectified bile acid (BA) dysmetabolism to alleviate hepatotoxicity. GW4064 treatment increased the reabsorption of conjugated BAs by inducing ASBT expression in the intestine. FXR/FGF15 activation in the presence of GW4064 decreased BA production by repressing the expression of key synthetases, including CYP7A1, CYP8B1, and CYP27A1[4]. GW4064 (20mg/kg; i.p.; twice) treatment alleviated hepatic inflammation in the Lipopolysaccharides(LPS)‑induced murine liver injury model as reflected by reduced serum levels of aspartate aminotransferase and pro‑inflammatory cytokine mRNA expression, including tumor necrosis factor‑α[5].
References:
[1]. Akwabi-Ameyaw, Adwoa, et al. "Conformationally constrained farnesoid X receptor (FXR) agonists: Naphthoic acid-based analogs of GW 4064." Bioorganic & medicinal chemistry letters 18.15 (2008): 4339-4343.
[2]. Guo J, et al. GW4064 enhances the chemosensitivity of colorectal cancer to oxaliplatin by inducing pyroptosis. Biochem Biophys Res Commun. 2021 Apr 9;548:60-66.
[3]. Singh N, et al. Synthetic FXR agonist GW4064 is a modulator of multiple G protein-coupled receptors. Mol Endocrinol. 2014 May;28(5):659-73.
[4]. Cao Y, et al. FXR agonist GW4064 improves liver and intestinal pathology and alters bile acid metabolism in rats undergoing small intestinal resection. Am J Physiol Gastrointest Liver Physiol. 2019 Aug 1;317(2):G108-G115.
[5]. Liu HM, et al. GW4064 attenuates lipopolysaccharide induced hepatic inflammation and apoptosis through inhibition of the Toll like receptor 4 mediated p38 mitogen activated protein kinase signaling pathway in mice. Int J Mol Med. 2018 Mar;41(3):1455-1462.
| Cell experiment [1]: | |
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Cell lines |
HEK cells |
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Preparation Method |
HEK cells in chamber slides were treated with 1μM GW4064 or ionomycin (1μM) for 30 minutes, and endogenous NFATc1 was detected by immunocytochemical analysis. The nuclei were stained with 4′,6-diamidino-2-phenylindole (DAPI). |
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Reaction Conditions |
1 μM; 30 minutes |
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Applications |
Consequent to calcineurin activation, nuclear translocation of endogenous NFATc1 was enhanced by GW4064 in a microscopy-based assay. |
| Animal experiment [2]: | |
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Animal models |
4-week-old female BALB/c-nude mice |
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Preparation Method |
HT-29 cells (5 × 106) in logarithmic growth phase were subcutaneously injected into the flanks of nude mice. When the palatable xenograft tumors were established, oxaliplatin (3mg/kg) and GW4064 (15mg/kg) as both single agents and in combination was injected intraperitoneally twice a week for 3 weeks. The tumor width (b) and length (a) were measured using the callipers every 3 days. |
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Dosage form |
15 mg/kg, i.p. |
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Applications |
Compared with using oxaliplatin or GW4064 only, combination of oxaliplatin and GW4064 in HT-29 cell line inhibited the tumor formation more significantly in vivo. |
References: | |
| Cas No. | 278779-30-9 | SDF | |
| Chemical Name | 3-[(E)-2-[2-chloro-4-[[3-(2,6-dichlorophenyl)-5-propan-2-yl-1,2-oxazol-4-yl]methoxy]phenyl]ethenyl]benzoic acid | ||
| Canonical SMILES | CC(C)C1=C(C(=NO1)C2=C(C=CC=C2Cl)Cl)COC3=CC(=C(C=C3)C=CC4=CC(=CC=C4)C(=O)O)Cl | ||
| Formula | C28H22Cl3NO4 | M.Wt | 542.85 |
| Solubility | ≥ 24.7mg/mL in DMSO | Storage | Store at -20°C |
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.8421 mL | 9.2106 mL | 18.4213 mL |
| 5 mM | 368.4 μL | 1.8421 mL | 3.6843 mL |
| 10 mM | 184.2 μL | 921.1 μL | 1.8421 mL |
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >99.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 28 reference(s) in Google Scholar.)