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| Other Sizes |
| Targets |
(24S,25)-Epoxycholesterol targets the liver X receptor (LXR), which is a nuclear receptor (LXRalpha/beta). LXR acts as a cholesterol sensor and regulates the transcription of genes involved in cholesterol efflux (ABCA1, ABCG1, APOE), lipid metabolism, and inflammation. Activation of LXR by this compound promotes reverse cholesterol transport, reduces foam cell formation, and inhibits the proliferation of certain cancer cells. It is an endogenous agonist, with CYP3A4 being involved in its formation from cholesterol.
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| ln Vitro |
24S,25-Epoxycholesterol (1-10 μM) upregulates LXR-related genes ABCA1, ABCG1, and APOE, promotes cholesterol efflux, thereby preventing foam cell formation, and blocks the proliferation of mouse and human glioma stem cells by eliminating cellular cholesterol[1][3]. 24S,25-Epoxycholesterol inhibits the proliferation and migration of HGC27, which is enhanced by knockout of LXRβ[2]. 24S,25-Epoxycholesterol (40 μM) inhibits HMG-CoA reductase and activates LXR, thereby inhibiting mevalonate-dependent isoprenoid production and enhancing ATP-binding cassette transporter G1 expression, inducing apoptosis of bone marrow-derived mouse mast cells (BMMC)[5].
In vitro, (24S,25)-Epoxycholesterol (1-10 uM) upregulates LXR target genes ABCA1, ABCG1, and APOE, promoting cholesterol efflux and preventing foam cell formation. It inhibits the proliferation and migration of HGC27 gastric cancer cells (1 uM, 18 h). At 40 uM, it inhibits HMG-CoA reductase and activates LXR, suppressing mevalonate-dependent isoprenoid generation and enhancing ABCG1 expression, which induces apoptosis in bone marrow-derived mast cells (BMMC). It also blocks the proliferation of mouse and human glioma stem cells. |
| ln Vivo |
24S,25-Epoxycholesterol (5 mM, intracerebroventricular injection) can enhance neurogenesis and limit neurodegeneration in midbrain dopamine neurons (mDA) in CYP46A1-overexpressing mice [4].
In vivo, (24S,25)-Epoxycholesterol (5 mM, single 1 uL intracerebroventricular (ICV) injection) enhances midbrain dopamine (mDA) neurogenesis and limits neurodegeneration in CYP46A1 overexpressing CD-1 mice. The compound activates LXR, leading to transcriptional regulation of target genes involved in cholesterol metabolism and neurogenesis. No data on cholesterol efflux or tumor growth inhibition in animal models are reported in the search results. |
| Enzyme Assay |
LXR binding of (24S,25)-Epoxycholesterol is measured by standard LXR agonist assays (e.g., a LXRalpha or LXRbeta reporter gene assay). COS-7 or HEK293 cells are co-transfected with a plasmid encoding the LXR ligand-binding domain fused to a Gal4 DNA-binding domain, and a Gal4-responsive luciferase reporter construct. Cells are treated with the compound (0.01-10 uM) for 24 hours, and luciferase activity is measured. An EC50 is calculated from the dose-response curve. Competitive binding assays using purified LXR protein and a radiolabeled LXR ligand can also be performed. No specific EC50 is reported.
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| Cell Assay |
Cell Proliferation Assay[2]
Cell Types: HGC27 Concentration: 1 μM Incubation Duration: 18 h Experimental Results: Inhibited proliferation of HGC27 Cell Migration Assay [2] Cell Types: HGC27 Concentration: 1 μM Incubation Duration: 18 h Experimental Results: Reduced HGC27 migration. For cellular assays, U937 or THP-1 macrophages (differentiated with PMA) are used. Cells are seeded in 6- or 24-well plates and treated with (24S,25)-Epoxycholesterol (1-10 uM) for 24-48 hours. The expression of LXR target genes (ABCA1, ABCG1, APOE) is measured by qPCR. Cholesterol efflux is assessed by loading cells with [3H]cholesterol, then measuring the amount of radiolabel released into the medium in the presence of an acceptor (e.g., apoA-I or HDL). For cancer cell assays, HGC27 gastric cancer cells or glioma stem cells are treated with the compound (0.1-10 uM), and cell proliferation is measured by MTT or CellTiter-Glo assays. Cell migration is assessed using a scratch wound healing assay. Apoptosis is measured by Annexin V/PI staining flow cytometry. |
| Animal Protocol |
Animal/Disease Models:GGPP induced mDA neurogenesis defect in CYP46A1 overexpressing CD-1 mice[4]
Doses: 5 mM Route of Administration: icv, 1 μL, single dosage Experimental Results: Increased levels of mDA neurons, blocked the GGPP induced decrease of double EdU and TH cells. For in vivo studies of neurogenesis, CD-1 mice overexpressing CYP46A1 (the cholesterol 24-hydroxylase) were used. (24S,25)-Epoxycholesterol (5 mM) was administered as a single 1 uL intracerebroventricular (ICV) injection using a stereotaxic apparatus. The mice were allowed to recover for 7 days, then the midbrain was dissected. The number of midbrain dopamine (mDA) neurons was assessed by immunohistochemistry for tyrosine hydroxylase (TH). The density of dopaminergic fibers in the striatum was quantified. Neurodegeneration was assessed by Fluoro-Jade C staining. No specific dosing or tumor model data are reported. |
| ADME/Pharmacokinetics |
(24S,25)-Epoxycholesterol (C2₇H44O2, MW = 400.64, purity ≥98%, CAS 77058-74-3) is a solid powder. For storage, the compound should be kept at -20degC for up to 3 years, sealed, and protected from light. For in vitro use, stock solutions in ethanol (16 mg/mL) can be prepared and stored at -20degC. For in vivo ICV injection, it can be formulated in saline with a small amount of DMSO or ethanol. No detailed PK parameters are reported.
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| Toxicity/Toxicokinetics |
No specific toxicity data for (24S,25)-Epoxycholesterol are reported in the search results. As a research-grade LXR agonist, it is not intended for human or veterinary use. Standard laboratory safety precautions for handling chemicals should be followed, including the use of gloves, lab coat, and safety goggles. LXR activation can lead to hepatic steatosis (fatty liver) and hypertriglyceridemia at high doses. No LD50 or formal toxicology studies are available.
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| References |
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| Additional Infomation |
24(S),25-Epoxycholesterol is a 3β-hydroxy-Δ(5)-steroid, a derivative of demethyl cholesterol, in which the double bond at positions 24-25 is oxidized to the corresponding epoxide (24S diastereomer). It is an oxysterol agonist of the hepatic X receptor. It has the function of acting as a hepatic X receptor agonist. It is a cholesterol alkylate compound, a 3β-hydroxy-Δ(5)-steroid, and an epoxysteroid. It is functionally related to demethyl cholesterol.
(24S,25)-Epoxycholesterol (24S,25-EC) is an oxysterol and an endogenous agonist of the liver X receptor (LXR). LXRalpha (NR1H3) is predominantly expressed in the liver, while LXRbeta (NR1H2) is expressed ubiquitously. LXRs are key regulators of cholesterol metabolism, and their activation promotes reverse cholesterol transport, which is the process by which excess cholesterol in peripheral tissues (including macrophages in atherosclerotic plaques) is transported to the liver for excretion. LXR agonists have been investigated for the treatment of atherosclerosis, cancer (by inducing apoptosis), and neurodegenerative diseases. However, clinical development of LXR agonists has been limited by side effects such as hypertriglyceridemia and hepatic steatosis. (24S,25)-Epoxycholesterol is for research use only and has not received regulatory approval for any indication. |
| Molecular Formula |
C27H44O2
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|---|---|
| Molecular Weight |
400.64
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| Exact Mass |
400.334
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| CAS # |
77058-74-3
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| PubChem CID |
3247059
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| Appearance |
White to off-white solid powder
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| Density |
1.05
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| Boiling Point |
496.4ºC at 760 mmHg
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| Flash Point |
201.2ºC
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| Index of Refraction |
1.544
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| LogP |
6.52
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
29
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| Complexity |
680
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| Defined Atom Stereocenter Count |
9
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| SMILES |
C[C@H](CC[C@H]1C(O1)(C)C)[C@H]2CC[C@@H]3[C@@]2(CC[C@H]4[C@H]3CC=C5[C@@]4(CC[C@@H](C5)O)C)C
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| InChi Key |
OSENKJZWYQXHBN-XVYZBDJZSA-N
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| InChi Code |
InChI=1S/C27H44O2/c1-17(6-11-24-25(2,3)29-24)21-9-10-22-20-8-7-18-16-19(28)12-14-26(18,4)23(20)13-15-27(21,22)5/h7,17,19-24,28H,6,8-16H2,1-5H3/t17-,19+,20+,21-,22+,23+,24+,26+,27-/m1/s1
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| Chemical Name |
(3S,8S,9S,10R,13R,14S,17R)-17-[(2R)-4-[(2S)-3,3-dimethyloxiran-2-yl]butan-2-yl]-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol
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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 | 2.4960 mL | 12.4800 mL | 24.9601 mL | |
| 5 mM | 0.4992 mL | 2.4960 mL | 4.9920 mL | |
| 10 mM | 0.2496 mL | 1.2480 mL | 2.4960 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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