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| 5mg |
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| Targets |
4β-Hydroxycholesterol is a potent LXRα and LXRβ agonist. By activating LXRα and LXRβ, the compound regulates the expression of genes involved in cholesterol metabolism, including ABCA1, ABCG1, and CYP7A1. This leads to the promotion of reverse cholesterol transport, the conversion of cholesterol to bile acids, and the inhibition of cholesterol absorption. The compound is also a major oxysterol cholesterol metabolite and a precursor for bile acid synthesis in human circulation. In vitro, at high concentrations, 4β-hydroxycholesterol inhibits cell growth and induces cell death. Its effects on cell viability are associated with loss of mitochondrial transmembrane potential, lysosomal membrane dysfunction, and superoxide anion overproduction. In vivo, plasma 4β-hydroxycholesterol is associated with lower blood pressure in healthy volunteers and regulates cholesterol transporters in peripheral tissues.
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| ln Vitro |
In vitro, at high concentrations, 4β-hydroxycholesterol inhibits cell growth and induces cell death associated with loss of mitochondrial transmembrane potential, lysosomal membrane dysfunction, and superoxide anion overproduction. The compound is a potent LXRα and LXRβ agonist. In cell-based assays, 4β-hydroxycholesterol is used to study LXR-mediated gene expression and cholesterol metabolism. Cells are treated with 4β-hydroxycholesterol at various concentrations (typically 1-100 μM), and the expression of LXR target genes (e.g., ABCA1, ABCG1, CYP7A1) is measured by qPCR or western blotting. The compound's effects on cell viability and apoptosis are assessed using MTT, LDH, or flow cytometry assays. Its effects on mitochondrial function are assessed by measuring mitochondrial membrane potential using fluorescent dyes (e.g., JC-1) and by measuring superoxide anion production. In studies of cholesterol metabolism, 4β-hydroxycholesterol is used to study the regulation of cholesterol transporters and reverse cholesterol transport.
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| ln Vivo |
In vivo, plasma 4β-hydroxycholesterol is associated with lower blood pressure in healthy volunteers and regulates cholesterol transporters in peripheral tissues, potentially activating reverse HDL cholesterol transport. The compound is a major oxysterol cholesterol metabolite and a precursor for bile acid synthesis in human circulation. In animal models, 4β-hydroxycholesterol is studied for its effects on cholesterol metabolism, blood pressure, and other physiological processes. The compound is also used as a biomarker of CYP3A4 activity, as its levels reflect the activity of CYP3A4 in the liver. However, comprehensive in vivo pharmacokinetic and toxicology studies have not been extensively reported. Further in vivo studies are needed to fully characterize the compound's physiological role and therapeutic potential. The compound is classified as a research chemical and is not approved for human use.
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| Enzyme Assay |
In vitro receptor binding assays for 4β-Hydroxycholesterol typically involve the use of LXRα and LXRβ receptors. For LXR binding assays, the receptor is incubated with radiolabeled or fluorescently labeled LXR ligands in the presence of varying concentrations of 4β-hydroxycholesterol. The binding affinity (IC₅₀ or Ki) is determined from competitive binding curves. For functional assays, cells expressing LXRα or LXRβ are treated with 4β-hydroxycholesterol, and LXR-mediated transcription is measured using reporter gene assays (e.g., luciferase reporter). The activation of LXR target genes is measured by qPCR or western blotting. Typical assay conditions include incubation at 25-37°C in appropriate buffer systems, with reaction products measured by scintillation counting, fluorescence, or chemiluminescence.
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| Cell Assay |
In vitro cell-based assays for 4β-Hydroxycholesterol are performed using hepatocyte, macrophage, or other cell lines that express LXRα and LXRβ. Cells are cultured in appropriate medium and treated with 4β-hydroxycholesterol at various concentrations (typically 1-100 μM) for 24-72 hours. Following treatment, cells are harvested, and the expression of LXR target genes (e.g., ABCA1, ABCG1, CYP7A1) is measured by qPCR or western blotting. Cholesterol efflux is measured by incubating cells with labeled cholesterol and measuring its appearance in the medium. Cell viability is assessed using MTT or LDH assays. Apoptosis is measured by flow cytometry using Annexin V/PI staining or by measuring caspase activity. Each experiment includes appropriate controls and is performed in triplicate to ensure statistical reliability.
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| Animal Protocol |
In vivo animal experiments with 4β-Hydroxycholesterol are conducted in mouse or rat models of cholesterol metabolism, cardiovascular disease, or liver disease. Typically, 8-12 week old rodents are used, and the compound is administered via oral gavage or intraperitoneal injection at doses ranging from 1-100 mg/kg. Following administration, blood samples are collected to measure plasma cholesterol, 4β-hydroxycholesterol, and other lipid parameters. At the end of the experiment, animals are euthanized, and tissues (liver, kidney, adipose) are collected for analysis. Gene expression is measured by qPCR, and protein levels are measured by western blotting. All animal procedures are conducted in accordance with institutional animal care and use committee guidelines, with appropriate sample sizes (typically n=6-10 per group) to ensure statistical power.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of 4β-Hydroxycholesterol are characteristic of an oxysterol. As a cholesterol metabolite, the compound is synthesized in the liver and circulates in the plasma. Its levels reflect the activity of CYP3A4 in the liver. The compound is metabolized through bile acid synthesis pathways and excreted in bile. The elimination half-life is determined by the rate of metabolism and excretion. As with all research chemicals, appropriate pharmacokinetic studies should be conducted to fully characterize the compound's absorption, distribution, metabolism, and excretion.
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| Toxicity/Toxicokinetics |
The toxicological profile of 4β-Hydroxycholesterol has not been extensively characterized in formal toxicology studies. As an endogenous oxysterol, the compound is naturally present in the body and is involved in cholesterol homeostasis. At high concentrations, 4β-hydroxycholesterol has been shown to inhibit cell growth and induce cell death in vitro. However, comprehensive toxicology studies including acute, subchronic, and chronic toxicity assessments have not been reported. The compound is classified as a research chemical and is not approved for human use.
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| References | |
| Additional Infomation |
4β-hydroxycholesterol is an oxosterol, formed when the hydrogen at the 4β position of cholesterol is replaced by a hydroxyl group. It is a product of cholesterol metabolism by the drug-metabolizing enzyme cytochrome P450 3A4, and is one of the main oxosterols in the human circulation. It functions as a metabolic byproduct. It is an oxosterol, 3β-sterol, diol, and 3β-hydroxy-Δ⁵-steroid. Its function is related to cholesterol.
4β-Hydroxycholesterol is a valuable research tool for studying cholesterol metabolism, LXR signaling, and CYP3A4 activity. It is an oxysterol metabolite of cholesterol formed primarily by CYP3A4 and CYP3A5. The compound is a major oxysterol cholesterol metabolite and a precursor for bile acid synthesis in human circulation. It has the molecular formula C₂₇H₄₆O₂. 4β-Hydroxycholesterol is a potent LXRα and LXRβ agonist. In vitro, at high concentrations, it inhibits cell growth and induces cell death. In vivo, plasma 4β-hydroxycholesterol is associated with lower blood pressure. It is not approved for any clinical indication and is strictly for research use only. |
| Molecular Formula |
C27H46O2
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|---|---|
| Molecular Weight |
402.65
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| Exact Mass |
402.349
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| CAS # |
17320-10-4
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| PubChem CID |
3247060
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| Appearance |
White to off-white solid powder
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| Density |
1.0±0.1 g/cm3
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| Boiling Point |
500.2±30.0 °C at 760 mmHg
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| Melting Point |
175-176 °C
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| Flash Point |
206.7±19.2 °C
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| Vapour Pressure |
0.0±2.9 mmHg at 25°C
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| Index of Refraction |
1.536
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| LogP |
8.8
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
29
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| Complexity |
624
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| Defined Atom Stereocenter Count |
9
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| SMILES |
C[C@H](CCCC(C)C)[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CC=C4[C@@]3(CC[C@@H]([C@@H]4O)O)C)C
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| InChi Key |
CZDKQKOAHAICSF-JSAMMMMSSA-N
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| InChi Code |
InChI=1S/C27H46O2/c1-17(2)7-6-8-18(3)20-11-12-21-19-9-10-23-25(29)24(28)14-16-27(23,5)22(19)13-15-26(20,21)4/h10,17-22,24-25,28-29H,6-9,11-16H2,1-5H3/t18-,19+,20-,21+,22+,24+,25-,26-,27-/m1/s1
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| Chemical Name |
(3S,4R,8S,9S,10R,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthrene-3,4-diol
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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) |
DMSO: 5 mg/mL (12.42 mM)
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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 | 2.4835 mL | 12.4177 mL | 24.8355 mL | |
| 5 mM | 0.4967 mL | 2.4835 mL | 4.9671 mL | |
| 10 mM | 0.2484 mL | 1.2418 mL | 2.4835 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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