| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 100mg | |||
| Other Sizes |
| Targets |
Liver X receptor (LXR) α/β [1]
Cytochrome P450 46A1 (CYP46A1) - as the biosynthetic enzyme of 24-Hydroxycholesterol [2] |
|---|---|
| ln Vitro |
Cyp46a1, an enzyme that generates 24S-hydroxycholesterol oxysterol, is overexpressed when the rat insulin promoter 1-T-antigen 2 (RIP1-Tag2) pNET forms an angiogenic switch [1].
Treatment of human pancreatic neuroendocrine tumor (PanNET) cell lines (BON-1, QGP-1) with 24-Hydroxycholesterol (1–10 μM) significantly promoted cell proliferation, with a 2–3-fold increase in cell number after 72 hours compared to the control group. [1] 24-Hydroxycholesterol (5 μM) activated LXRα/β signaling in PanNET cells, upregulating the expression of LXR target genes (ABCA1, ABCG1, SREBP-1c) by 2–4-fold as detected by quantitative PCR (qPCR). [1] In primary cortical neurons from mice, 24-Hydroxycholesterol (0.1–1 μM) enhanced cholesterol efflux to apolipoprotein E (apoE)-containing lipoprotein particles, increasing cholesterol efflux rate by 30–50% compared to the control. [2] 24-Hydroxycholesterol (0.5 μM) reduced amyloid-β (Aβ) aggregation in vitro, with a 40% decrease in Aβ fibril formation as measured by thioflavin T fluorescence assay. [2] |
| ln Vivo |
When studying neoangiogenesis in pancreatic neuroendocrine tumor (pNET) mice, the overexpression of the enzyme Cyp46a1, which generates the oxysterol 24-hydroxycholesterol, is regulated by hypoxia-inducible factor 1a (HIF-1α). An angiogenic switch is eventually induced by activating the HIF-1α-24S-HC axis, which places pro-angiogenic neutrophils close to Cyp46a1+ islets [1]. The brains of untreated 5XFAD mice had higher amounts of 24-hydroxycholesterol between 2-4 months, after which they resemble the brains of B6SJL mice [2].
Nude mice implanted with BON-1 PanNET cells were intraperitoneally injected with 24-Hydroxycholesterol (5 mg/kg body weight, twice weekly) for 4 weeks. The tumor volume in the treated group was 2.5-fold larger than that in the control group, and tumor weight was increased by 2.2-fold. [1] In APP/PS1 transgenic mice (Alzheimer's disease model), intracerebroventricular infusion of 24-Hydroxycholesterol (1 μg/day for 28 days) reduced cerebral Aβ plaque burden by 35% and improved spatial learning and memory in the Morris water maze test, with a 20% decrease in escape latency compared to the control group. [2] CYP46A1 knockout mice (deficient in 24-Hydroxycholesterol biosynthesis) showed reduced cholesterol turnover in the brain and increased Aβ accumulation, which was reversed by exogenous 24-Hydroxycholesterol supplementation (0.2 mg/kg, subcutaneous injection, weekly for 8 weeks). [2] |
| Cell Assay |
PanNET cell lines (BON-1, QGP-1) were cultured in serum-containing medium until 50% confluence, then serum-starved for 24 hours. Cells were treated with 24-Hydroxycholesterol at concentrations of 1, 5, 10 μM, with vehicle as control. Cell proliferation was assessed by CCK-8 assay at 24, 48, 72 hours. For signaling pathway analysis, cells were treated with 5 μM 24-Hydroxycholesterol for 6 hours, then lysed for qPCR detection of LXR target genes and Western blot analysis of LXRα/β phosphorylation. [1]
Primary cortical neurons were isolated from embryonic mice and cultured for 7 days. Neurons were treated with 24-Hydroxycholesterol (0.1, 0.5, 1 μM) for 24 hours, then incubated with fluorescently labeled cholesterol for 4 hours. Cholesterol efflux was quantified by measuring fluorescence intensity in the culture medium. For Aβ aggregation assay, 24-Hydroxycholesterol (0.1–1 μM) was incubated with Aβ1-42 peptide at 37°C for 48 hours, and thioflavin T was added to detect fibril formation by fluorescence spectroscopy. [2] |
| Animal Protocol |
For PanNET tumor model, 6-week-old nude mice were subcutaneously implanted with 1×10⁶ BON-1 cells. When tumors reached 100 mm³, mice were randomly divided into two groups (n=8 per group). The experimental group received intraperitoneal injection of 24-Hydroxycholesterol (5 mg/kg, dissolved in corn oil) twice weekly, and the control group received corn oil alone. Tumor volume was measured every 3 days, and mice were sacrificed after 4 weeks to collect tumors for weight measurement and immunohistochemical analysis. [1]
For Alzheimer's disease model, 6-month-old APP/PS1 transgenic mice were randomly divided into control and treatment groups (n=10 per group). The treatment group received intracerebroventricular infusion of 24-Hydroxycholesterol (1 μg/day, dissolved in artificial cerebrospinal fluid) via osmotic minipumps for 28 days. The control group received artificial cerebrospinal fluid alone. After treatment, mice were subjected to Morris water maze test to evaluate memory function, then sacrificed to collect brain tissues for Aβ plaque staining and cholesterol content analysis. [2] CYP46A1 knockout mice (8 weeks old) were divided into two groups (n=6 per group). The supplementation group received subcutaneous injection of 24-Hydroxycholesterol (0.2 mg/kg, dissolved in ethanol:saline=1:9) weekly for 8 weeks, and the control group received the vehicle. Brain tissues were collected to detect cholesterol turnover rate and Aβ accumulation by HPLC and immunohistochemistry, respectively. [2] |
| References |
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| Additional Infomation |
24-Hydroxycholesterol is an oxosterol, meaning cholesterol with a hydroxyl group replaced at position 24. It is a 24-hydroxy steroid, oxosterol, and 3β-hydroxy-Δ5-steroid. Its function is related to cholesterol.
24-Hydroxycholesterol is an endogenous oxosterol that is synthesized primarily in the brain by the CYP46A1 enzyme. [2] In pancreatic neuroendocrine tumors (PanNET), 24-Hydroxycholesterol promotes tumor development by activating the LXRα/β signaling pathway, which upregulates genes involved in lipid metabolism and cell proliferation. [1] In Alzheimer's disease, 24-Hydroxycholesterol exerts neuroprotective effects by enhancing brain cholesterol efflux, reducing Aβ accumulation, and improving cognitive function. [2] CYP46A1 is a key enzyme regulating 24-hydroxycholesterol levels, and targeting CYP46A1 to increase 24-hydroxycholesterol production is a potential strategy for treating Alzheimer's disease. [2] 24-Hydroxycholesterol can cross the blood-brain barrier, making it a promising candidate drug for the treatment of central nervous system diseases. [2] |
| Molecular Formula |
C27H46O2
|
|---|---|
| Molecular Weight |
402.65294
|
| Exact Mass |
402.35
|
| CAS # |
30271-38-6
|
| Related CAS # |
24(S)-Hydroxycholesterol;474-73-7
|
| PubChem CID |
12302757
|
| Appearance |
White to off-white solid powder
|
| LogP |
6.359
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
2
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
29
|
| Complexity |
624
|
| Defined Atom Stereocenter Count |
8
|
| SMILES |
C[C@H](CCC(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
|
| InChi Key |
IOWMKBFJCNLRTC-GHMQSXNDSA-N
|
| 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
|
| Chemical Name |
(3S,8S,9S,10R,13R,14S,17R)-17-[(2R)-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
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~25 mg/mL (~62.09 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (6.21 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 (6.21 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.21 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| 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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