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| Targets |
The primary target of 24(R)-Hydroxycholesterol is the liver X receptors (LXRα and LXRβ). As an oxysterol nuclear receptor modulator, 24R-HC can directly bind to and activate LXRα and LXRβ . Studies have shown that 24R-HC activates LXRα and LXRβ with EC₅₀ values of 7 μM and 4 μM, respectively, which are slightly lower than those of the natural isomer 24S-HC (EC₅₀ values of 4 μM and 3 μM, respectively) . Position-specific monooxidation of the sterol side chain is required for LXR binding and activation by this compound .
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| ln Vitro |
In vitro studies demonstrate that 24(R)-Hydroxycholesterol can directly bind to LXRs and activate transcriptional activity . In cell-based reporter gene assays, 24R-HC activates LXRα and LXRβ with EC₅₀ values of 7 μM and 4 μM, respectively . As an oxysterol ligand for LXRs, this compound regulates the expression of multiple genes involved in cholesterol and bile acid metabolism. Studies also indicate that enhanced binding and activation can be achieved with 24-oxo ligands in combination with 24R-HC . As a nuclear receptor modulator, 24R-HC is an important tool molecule for studying LXR signaling pathways and cholesterol metabolism regulation.
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| ln Vivo |
Currently, publicly available data on the in vivo activity of 24(R)-Hydroxycholesterol are limited. This compound primarily participates in in vivo metabolic processes as an intermediate in bile acid metabolism . 24R-HC is a substrate for cytochrome P450 39A1 (CYP39A1), a liver-specific enzyme that catalyzes the conversion of 24R-HC to 7α,24R-dihydroxycholesterol . Studies also show that both 24R-HC and 24S-HC are substrates for hepatic cholesterol 7α-hydroxylase (CYP7A), participating in the production of 7α-hydroxylated bile acids . Unlike 24S-HC, the production of 24R-HC is independent of CYP46A1 .
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| Enzyme Assay |
Receptor binding studies for 24(R)-Hydroxycholesterol can be conducted using radioligand binding assays. A standard protocol includes: 1) Prepare nuclear extracts or recombinant receptor proteins expressing human LXRα or LXRβ receptors; 2) Dissolve 24R-HC in DMSO (stock concentration 10-50 mM) and dilute to various concentrations (0.1-30 μM) with binding buffer (containing 50 mM Tris-HCl pH 7.4, 150 mM NaCl, 0.1% BSA); 3) Add radiolabeled tracer (such as [³H]-24S-HC or [³H]-T0901317); 4) Incubate for 1-2 hours at 4°C or room temperature to reach binding equilibrium; 5) Terminate the reaction by rapid filtration or centrifugation, washing to remove unbound ligand; 6) Measure radioactivity using a liquid scintillation counter and calculate IC₅₀ and Kᵢ values from competition binding curves. Fluorescence polarization techniques can also be employed to detect receptor-ligand interactions .
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| Cell Assay |
The in vitro cell assay protocol for 24(R)-Hydroxycholesterol is as follows: 1) Seed target cells (such as HEK293 cells, HepG2 hepatoma cells, or macrophages) in culture plates and culture to appropriate density at 37°C with 5% CO₂; 2) Co-transfect cells with LXR reporter gene plasmids (luciferase reporter plasmid containing LXR response elements) and reference plasmids using lipofection methods ; 3) 24 hours after transfection, treat cells with various concentrations of 24R-HC (typically 0.1-30 μM) for 18-24 hours; 4) Lyse cells and measure luciferase activity using a luciferase reporter assay system; 5) Calculate the relative fold activation at each concentration and determine EC₅₀ values by nonlinear regression analysis. LXR target gene (such as ABCA1, SREBP-1c) protein expression levels can also be detected by Western blot .
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| Animal Protocol |
Currently, in vivo animal data for 24(R)-Hydroxycholesterol are limited in the available literature. Based on the metabolic characteristics of this compound, potential research protocols could include the following: 1) Use 6-8 week old male C57BL/6 mice; 2) Administer 24R-HC via tail vein intravenous injection or intraperitoneal injection (doses to be determined through preliminary experiments, with reference to 24S-HC study doses of 1-10 mg/kg); 3) Collect plasma and liver tissue at various time points post-administration (e.g., 0, 1, 2, 4, 8, 12, 24 hours); 4) Quantify 24R-HC and its metabolite concentrations in plasma and tissues by LC-MS/MS; 5) Measure plasma levels of total cholesterol, triglycerides, and bile acids; 6) Assess mRNA expression changes of LXR target genes (such as Cyp7a1, Abca1, Srebp-1c) in the liver by qPCR. Additionally, CYP46A1 transgenic mouse models could be used to study the differential metabolism of 24R-HC and 24S-HC in vivo .
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| ADME/Pharmacokinetics |
The pharmacokinetic characteristics of 24(R)-Hydroxycholesterol are closely related to its physiological function as an intermediate in bile acid metabolism. This compound is a substrate for cytochrome P450 39A1 (CYP39A1), a liver-specific enzyme that catalyzes the 7α-hydroxylation of 24R-HC . Additionally, both 24R-HC and 24S-HC serve as substrates for hepatic cholesterol 7α-hydroxylase (CYP7A), participating in the biosynthesis of primary bile acids . 24S-Hydroxycholesterol is generally more abundant in human tissues than 24R-hydroxycholesterol, suggesting that the in vivo levels of 24R-HC are relatively lower . 24R-HC can be further metabolized in vivo to 7α-hydroxylated bile acids . Unlike 24S-HC, the production of 24R-HC is independent of cerebral CYP46A1 and is primarily formed through non-CYP46A1-dependent pathways .
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| Toxicity/Toxicokinetics |
Systematic toxicological data for 24(R)-Hydroxycholesterol are currently limited. As an endogenous metabolite and nuclear receptor modulator, 24R-HC generally does not exhibit obvious toxicity at physiological concentrations. In vitro studies show that this compound exerts its biological effects as an LXR ligand in the micromolar concentration range . LXR activation has dual effects: it promotes cholesterol efflux and anti-inflammatory responses on one hand, but may induce hepatic steatosis and triglyceride synthesis on the other hand, suggesting that long-term high-concentration exposure may carry metabolic risks. The toxicological profile of 24R-HC differs from its stereoisomer 24S-HC, which exhibits neurotoxicity at higher concentrations in neuronal cells. No systematic evaluations of carcinogenicity, reproductive toxicity, or developmental toxicity for 24R-HC are currently available. This compound is for research use only, and standard chemical safety practices should be followed during handling and storage.
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| References | |
| Additional Infomation |
(24R)-24-hydroxycholesterol is a 24-hydroxycholesterol with an R configuration at position 24. It functions as a nuclear receptor modulator and a mouse metabolite.
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| Molecular Formula |
C27H46O2
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| Molecular Weight |
402.65
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| Exact Mass |
402.349
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| Elemental Analysis |
C, 80.54; H, 11.52; O, 7.95
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| CAS # |
27460-26-0
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| Related CAS # |
24(S)-Hydroxycholesterol;474-73-7; 27460-26-0; 30271-38-6; 144154-78-9
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| PubChem CID |
10135759
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| Appearance |
Solid Powder
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| Density |
1.0±0.1 g/cm3
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| Boiling Point |
513.1±23.0 °C at 760 mmHg
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| Flash Point |
213.5±17.2 °C
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| Vapour Pressure |
0.0±3.0 mmHg at 25°C
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| Index of Refraction |
1.536
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| LogP |
7.66
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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](CC[C@H](C(C)C)O)[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CC=C4[C@@]3(CC[C@@H](C4)O)C)C
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| InChi Key |
IOWMKBFJCNLRTC-RNCHBCSGSA-N
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| InChi Code |
InChI=1S/C27H46O2/c1-17(2)25(29)11-6-18(3)22-9-10-23-21-8-7-19-16-20(28)12-14-26(19,4)24(21)13-15-27(22,23)5/h7,17-18,20-25,28-29H,6,8-16H2,1-5H3/t18-,20+,21+,22-,23+,24+,25-,26+,27-/m1/s1
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| Chemical Name |
(3S,8S,9S,10R,13R,14S,17R)-17-[(2R,5R)-5-hydroxy-6-methylheptan-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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| Synonyms |
(24R)-24-hydroxycholesterol; 24(R)-hydroxycholesterol; (24R)-hydroxycholesterol; 24-Epicerebrosterol; 27460-26-0;
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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) |
Typically soluble in DMSO (e.g. 10 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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