| Size | Price | Stock | Qty |
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| 100mg |
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| 500mg | |||
| Other Sizes |
| Targets |
GW6340 specifically targets the liver X receptor (LXR), a nuclear receptor that functions as a cholesterol sensor and regulates the expression of genes involved in lipid metabolism, cholesterol homeostasis, and inflammation. LXR exists in two isoforms, LXRα and LXRβ, which have distinct tissue distribution patterns and functions. GW6340 acts as an intestinal-specific LXR agonist, meaning it preferentially activates LXR in the gut while limiting systemic LXR activation. This tissue selectivity is achieved through the compound's pharmacokinetic properties, which restrict its distribution to the intestinal tract. By activating LXR in the intestine, GW6340 promotes the expression of target genes such as ABCA1 and ABCG1, which mediate cholesterol efflux and macrophage reverse cholesterol transport.
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| ln Vitro |
In vitro, GW6340 activates LXR-mediated transcriptional activity in cell-based reporter assays. The compound promotes macrophage reverse cholesterol transport (mRCT), a process by which cholesterol is removed from macrophage foam cells in the arterial wall and transported to the liver for biliary excretion. In intestinal cells, GW6340 activates LXR target genes involved in cholesterol absorption, efflux, and metabolism. The compound's intestinal specificity is a notable feature, as it allows researchers to study the effects of intestinal LXR activation without the confounding systemic effects associated with non-selective LXR agonists. GW6340 has been studied for its potential anticancer activity, though the specific mechanisms are still under investigation.
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| ln Vivo |
In vivo, GW6340 has been investigated in animal models of atherosclerosis and cancer. As an intestinal-specific LXR agonist, the compound promotes macrophage reverse cholesterol transport (mRCT) in vivo, facilitating the removal of cholesterol from peripheral tissues. By activating intestinal LXR, GW6340 upregulates the expression of cholesterol transporters such as ABCA1 and ABCG1, which mediate the efflux of cholesterol from macrophages to apolipoprotein A-I and HDL particles. The compound's intestinal specificity limits systemic LXR activation, potentially reducing the risk of LXR-mediated side effects such as hepatic steatosis and hypertriglyceridemia. GW6340 has also been evaluated for potential anticancer activity in preclinical models.
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| Enzyme Assay |
The binding and activation of LXR by GW6340 are typically assessed using cell-based reporter gene assays. In these assays, cells are transfected with a luciferase reporter construct containing LXR response elements (LXREs) upstream of a minimal promoter, along with expression plasmids for LXRα or LXRβ. Cells are treated with varying concentrations of GW6340, and luciferase activity is measured to quantify LXR transcriptional activation. EC50 values are calculated from dose-response curves. The compound's intestinal specificity can be confirmed by comparing activity in intestinal cell lines versus other cell types. Selectivity for LXR over other nuclear receptors can be assessed using similar reporter assays with response elements for other nuclear receptors.
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| Cell Assay |
Cellular assays for GW6340 are performed using intestinal cell lines (such as Caco-2) and macrophage cell lines (such as THP-1-derived macrophages). Cells are treated with varying concentrations of the compound for specified time periods. LXR target gene expression, including ABCA1, ABCG1, and other cholesterol transport-related genes, is quantified by qRT-PCR and Western blotting. Cholesterol efflux assays are performed by loading cells with radiolabeled or fluorescent cholesterol, then measuring the amount of cholesterol released into the medium in the presence of cholesterol acceptors such as apolipoprotein A-I or HDL. The compound's intestinal specificity can be assessed by comparing LXR activation in intestinal versus hepatic cell lines.
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| Animal Protocol |
In vivo studies of GW6340 are conducted in rodent models of atherosclerosis and cancer. The compound is typically formulated in vehicles such as 10% DMSO + 40% PEG300 + 5% Tween 80 + 45% saline at concentrations up to 3.3 mg/mL. Administration routes may include oral gavage or intraperitoneal injection. Pharmacodynamic endpoints include assessment of macrophage reverse cholesterol transport using radiolabeled cholesterol tracing techniques, measurement of plasma cholesterol and lipoprotein levels, and evaluation of atherosclerotic plaque burden in atherosclerosis models. In cancer models, tumor growth inhibition and survival are monitored. Gene expression analysis of LXR target genes in intestinal tissues confirms target engagement.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of GW6340 (molecular weight 581.07, molecular formula C33H32ClF3N2O2) have been characterized. The compound has a calculated density of 1.242 g/cm³ at 20°C and is soluble in DMSO at concentrations up to 80 mg/mL (137.68 mM). For in vivo administration, the compound can be formulated in 10% DMSO + 40% PEG300 + 5% Tween 80 + 45% saline, with sonication recommended to achieve complete dissolution. Storage recommendations include powder storage at -20°C for up to 3 years and solution storage at -80°C for 1 year. The compound's intestinal specificity suggests limited systemic absorption, which is a key pharmacokinetic feature that enables its gut-restricted activity.
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| Toxicity/Toxicokinetics |
GW6340 is intended for research use only and is not approved for human therapeutic applications. Comprehensive toxicological evaluations have been conducted as part of preclinical development. The compound's intestinal specificity is expected to limit systemic exposure and reduce the risk of LXR-mediated side effects such as hepatic steatosis and hypertriglyceridemia that have been observed with non-selective LXR agonists. Standard safety pharmacology assessments would include evaluation of effects on lipid metabolism, liver function, and gastrointestinal physiology. Researchers should handle the compound with appropriate safety precautions for research chemicals.
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| References | |
| Additional Infomation |
GW6340 is a research-grade compound used as a pharmacological tool for studying LXR biology and the therapeutic potential of intestinal LXR activation. LXR is a nuclear receptor that functions as a cholesterol sensor and regulates genes involved in lipid metabolism, cholesterol homeostasis, and inflammation. Intestinal LXR activation promotes macrophage reverse cholesterol transport (mRCT), a process that facilitates the removal of cholesterol from peripheral tissues. GW6340's intestinal specificity is a key feature that enables researchers to study the effects of gut-restricted LXR activation without the confounding systemic effects of non-selective LXR agonists. The compound is being investigated for potential applications in studying atherosclerosis and cancer. GW6340 is available with purity ≥98-99.79%.
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| Molecular Formula |
C33H32CLF3N2O2
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| Molecular Weight |
581.067598342896
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| Exact Mass |
580.21
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| Elemental Analysis |
C, 68.21; H, 5.55; Cl, 6.10; F, 9.81; N, 4.82; O, 5.51
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| CAS # |
405910-78-3
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| PubChem CID |
10231936
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| Appearance |
Off-white to light yellow ointment
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| LogP |
7.5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
13
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| Heavy Atom Count |
41
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| Complexity |
754
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=C(C=C1)C(CN(CCCOC2=CC=CC(=C2)CC(=O)N)CC3=C(C(=CC=C3)C(F)(F)F)Cl)C4=CC=CC=C4
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| InChi Key |
ZVWVNNYZOBNFFJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C33H32ClF3N2O2/c34-32-27(15-8-17-30(32)33(35,36)37)22-39(18-9-19-41-28-16-7-10-24(20-28)21-31(38)40)23-29(25-11-3-1-4-12-25)26-13-5-2-6-14-26/h1-8,10-17,20,29H,9,18-19,21-23H2,(H2,38,40)
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| Chemical Name |
2-(3-(3-((2-chloro-3-(trifluoromethyl)benzyl)(2,2-diphenylethyl)amino)propoxy)phenyl)acetamide
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| Synonyms |
GW6340; GW 6340; GW-6340
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7210 mL | 8.6048 mL | 17.2096 mL | |
| 5 mM | 0.3442 mL | 1.7210 mL | 3.4419 mL | |
| 10 mM | 0.1721 mL | 0.8605 mL | 1.7210 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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