| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
The Glucocorticoid Receptor (GR), which is a nuclear receptor that upon ligand binding translocates to the nucleus to regulate gene expression.
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| ln Vitro |
In cell-free assays, (R)-GSK866 binds to the glucocorticoid receptor with an IC50 of 4.6 nM, indicating it is a potent agonist.
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| ln Vivo |
This entry is not available. A general principle for glucocorticoid receptor agonists is they induce the expression of anti-inflammatory proteins and suppress the expression of pro-inflammatory proteins.
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| Enzyme Assay |
A general protocol for assessing glucocorticoid receptor binding involves a radioligand binding assay. Cytosol preparations from cells expressing the human glucocorticoid receptor are incubated with [3H]-Dexamethasone (a high-affinity GR ligand) at a concentration of 10 nM in a buffer (10 mM Tris-HCl, pH 7.4, 10% glycerol, 2 mM DTT, 5 mM sodium molybdate) at 4degC for 16-20 hours. To determine the binding affinity of a test compound (e.g., (R)-GSK866), the incubation is performed in the presence of varying concentrations of the compound. Non-specific binding is determined using a 500-fold molar excess of unlabeled dexamethasone. The bound and free fractions are separated using a charcoal-dextran method or by filtration through GF/C filters. The radioactivity is counted, and IC50 values are calculated.
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| Cell Assay |
A general protocol for evaluating glucocorticoid receptor (GR) agonists in cells involves using a luciferase reporter gene assay. A549 cells are co-transfected with a plasmid containing a glucocorticoid response element (GRE) driving a luciferase reporter gene and a plasmid encoding the human GR. After 24 hours of transfection, the cells are treated with various concentrations of the test compound (e.g., (R)-GSK866) for 18-24 hours. The cells are then lysed, and the luciferase activity is measured using a luminometer. The EC50 value is calculated by determining the concentration of the compound that produces half-maximal activation of the reporter gene. Dexamethasone is used as a positive control.
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| Animal Protocol |
A general in vivo protocol for evaluating the anti-inflammatory effects of GR agonists involves the carrageenan-induced paw edema model in rats. Male Sprague-Dawley rats are orally administered the test compound (e.g., (R)-GSK866) at doses of 0.1, 0.3, and 1 mg/kg, one hour before subplantar injection of 0.1 mL of 1% carrageenan in the right hind paw. Paw volume is measured at 0, 1, 2, 3, and 4 hours after carrageenan injection using a plethysmometer. The percentage inhibition of paw edema is calculated for each treatment group relative to the vehicle control group. The anti-inflammatory potency of (R)-GSK866 is compared to that of the standard GR agonist, dexamethasone.
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| ADME/Pharmacokinetics |
This entry is not available.
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| References | |
| Additional Infomation |
This entry is not available. There is also an (S)-enantiomer of GSK866, which may have different biological properties. The racemic mixture of these enantiomers is often studied to understand the significance of chirality in drug-receptor interactions. The molecular formula for (R)-GSK866 is C23H21Cl2F4N5O3.
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| Molecular Formula |
C23H21CL2F4N5O3
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|---|---|
| Molecular Weight |
562.34
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| CAS # |
1094607-80-3
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| Appearance |
White to off-white solid powder
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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 |
| 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 | 1.7783 mL | 8.8914 mL | 17.7828 mL | |
| 5 mM | 0.3557 mL | 1.7783 mL | 3.5566 mL | |
| 10 mM | 0.1778 mL | 0.8891 mL | 1.7783 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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