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Purity: ≥98%
GSK2033 is a novel, potent and cell-active LXR (liver X receptor) antagonist with pIC50s of 7 and 7.4 for LXRα or LXRβ. It enhances T-cell proliferation and blocks T 0901317-antiproliferative activity on T-cells and is cell permeable. GSK2033 displays systemic exposure. Although GSK2033 performed as expected in cell-based models as a LXR inverse agonist, it displayed unexpected activity in the mouse NAFLD model. The expression of lipogenic enzyme genes such as fatty acid synthase and sterol regulatory binding protein 1c were induced rather than suppressed and no effect on hepatic steatosis was found. Further characterization of the specificity of GSK2033 revealed that it displayed a significant degree of promiscuity, targeting a number of other nuclear receptors that could clearly alter hepatic gene expression.
| ln Vitro |
GSK2033 is an LXR antagonist having pIC50s of 7.4 for LXRβ and 7.4 for LXRβ, respectively. In the full-length LXRα or full-length LXRβ co-transfection experiments, GSK2033 dose-dependently suppressed basal transcription with IC50s of 17 nM and 9 nM, respectively. GSK2033 exhibits dose-dependent inhibition of ABCA1-driven luciferase reporter gene transcription, with an IC50 of 52 nM for LXRα and 10 nM for LXRβ. Additionally, GSK2033 suppresses SREBP1 and fatty acid synthase (FASN) expression [2].
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| ln Vivo |
The one-month GSK2033 therapy showed no discernible impact on the levels of liver triglycerides. The administration of GSK2033 had no effect on plasma triglyceride levels [2].
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| References |
[1]. Zuercher WJ, et al. Discovery of tertiary sulfonamides as potent liver X receptor antagonists. J Med Chem. 2010 Apr 22;53(8):3412-6.
[2]. Griffett K, et al. Promiscuous activity of the LXR antagonist GSK2033 in a mouse model of fatty liver disease. Biochem Biophys Res Commun. 2016 Oct 21;479(3):424-428 |
| Molecular Formula |
C29H28NO5F3S2
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|---|---|
| Molecular Weight |
591.662
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| CAS # |
1221277-90-2
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| SMILES |
O=S(C1=C(C)C=C(C)C=C1C)(N(CC2=CC=C(C3=CC=CC(S(=O)(C)=O)=C3)C=C2)CC4=CC=C(C(F)(F)F)O4)=O
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| InChi Key |
PSOXOVKYGWBTPB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C29H28F3NO5S2/c1-19-14-20(2)28(21(3)15-19)40(36,37)33(18-25-12-13-27(38-25)29(30,31)32)17-22-8-10-23(11-9-22)24-6-5-7-26(16-24)39(4,34)35/h5-16H,17-18H2,1-4H3
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| Chemical Name |
2,4,6-Trimethyl-N-[[3'-(methylsulfonyl)[1,1'-biphenyl]-4-yl]methyl]-N-[[5-(trifluoromethyl)-2-furanyl]methyl]benzenesulfonamide
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| Synonyms |
GSK-2033; GSK2033; GSK 2033.
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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) |
DMSO : ~30 mg/mL (~50.70 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 3 mg/mL (5.07 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 30.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 3 mg/mL (5.07 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 30.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6902 mL | 8.4508 mL | 16.9016 mL | |
| 5 mM | 0.3380 mL | 1.6902 mL | 3.3803 mL | |
| 10 mM | 0.1690 mL | 0.8451 mL | 1.6902 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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