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| 25mg |
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| 50mg |
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| 100mg |
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Purity: ≥98%
SR9238 is the first selective synthetic LXR (Liver X receptor) inverse antagonist with IC50s of 214 nM and 43 nM for LXRα and LXRβ, respectively. SR9238 can effectively suppresses hepatic lipogenesis, inflammation, and hepatic lipid accumulation in a mouse model of non-alcoholic hepatosteatosis. SR9238 displays high potency for both LXRα and LXRβ (40-200 nM IC50) and was designed to display liver specificity so as to avoid potential side effects due to suppression of LXR in the periphery. Unexpectedly, treatment of diet-induced obese mice with SR9238 suppressed plasma cholesterol levels. These data indicate that liver-selective LXR inverse agonists such as SR9238 may hold utility in the treatment of liver disease. Fatty liver, which often accompanies obesity and type 2 diabetes, frequently leads to a much more debilitating hepatic disease including non-alcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. Current pharmacological therapies lack conclusive efficacy and thus treatment options are limited. Novel therapeutics that suppress either hepatic lipogenesis and/or hepatic inflammation may be useful.
| ln Vitro |
The results of the cell-based co-transfection assay demonstrated that SR9238 is a synthetic LXR inverse agonist, with an IC50 for LXRα of 214 nM and LXRβ of 43 nM. Additionally, SR9238 successfully suppresses the luciferase reporter gene's transcription, which is triggered by the fatty acid synthase (Fasn) promoter. The results showed that SR9238 increased the interaction between LXRα and LXRβ and the CoRNR box peptides obtained from NCoR (NCoR ID1 and NCoR ID2), but decreased the interaction with the coactivator NR box peptide produced from TRAP220. For both LXRα and LXRβ, SR9238-induced recruitment of CoRNR box peptides was dose-dependent. Fasn and Srebp1c mRNA expression was significantly reduced in HepG2 cells treated with SR9238 [1].
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| ln Vivo |
Two hours after SR9238 injection, the liver contained about 6 μM of the drug, whereas the plasma contained no SR9238 at all. SR9238 can alternatively be taken orally or administered intraperitoneally to detect its presence in the gut. The livers of the mice treated with SR9238 had a markedly lower lipid content. The findings demonstrated that, in comparison to mice treated with vehicle, the expression of Tnfa and Il1b was much lower in SR9238-treated mice (about 80% and >95%, respectively). In line with SR9238's positive effects on nonalcoholic steatohepatitis (NASH), F4/80 staining intensity was considerably lower in DIO mice treated with SR9238 than in DIO mice treated with vehicle. In comparison to rats treated with a vehicle, SR9238 therapy had no effect on body weight or body fat composition during the experiment. Hepatic steatosis, liver inflammation, and hepatocellular damage brought on by diet are all inhibited by SR9238 treatment [1].
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| References |
| Molecular Formula |
C31H33NO7S2
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|---|---|---|
| Molecular Weight |
595373
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| Exact Mass |
595.169
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| Elemental Analysis |
C, 62.50; H, 5.58; N, 2.35; O, 18.80; S, 10.76
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| CAS # |
1416153-62-2
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| Related CAS # |
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| PubChem CID |
71478195
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
787.7±70.0 °C at 760 mmHg
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| Flash Point |
430.2±35.7 °C
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| Vapour Pressure |
0.0±2.7 mmHg at 25°C
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| Index of Refraction |
1.590
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| LogP |
5.79
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
41
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| Complexity |
1060
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S(C1C(C)=CC(C)=CC=1C)(N(CC1=CC=C(C(=O)OCC)O1)CC1C=CC(C2C=CC=C(C=2)S(C)(=O)=O)=CC=1)(=O)=O
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| InChi Key |
HDZWHJYZJWLTAG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C31H33NO7S2/c1-6-38-31(33)29-15-14-27(39-29)20-32(41(36,37)30-22(3)16-21(2)17-23(30)4)19-24-10-12-25(13-11-24)26-8-7-9-28(18-26)40(5,34)35/h7-18H,6,19-20H2,1-5H3
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| Chemical Name |
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (4.20 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 25.0 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: ≥ 2.5 mg/mL (4.20 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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 | 0.0017 mL | 0.0084 mL | 0.0168 mL | |
| 5 mM | 335.9239 nL | 0.0017 mL | 0.0034 mL | |
| 10 mM | 167.9619 nL | 839.8097 nL | 0.0017 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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