7-Dehydrocholesterol
(Synonyms: 7-去氢胆固醇) 目录号 : GC33450
An immediate precursor to cholesterol
Cas No.:434-16-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
7-dehydro Cholesterol (7-DHC) is an immediate precursor of cholesterol.1 It is reduced to cholesterol by the enzyme 3β-hydroxysterol-Δ7-reductase (DHCR7) in the last step of cholesterol biosynthesis. 7-DHC accumulates in Smith-Lemli-Opitz syndrome (SLOS), a disorder characterized by a mutation in the DHCR7 gene and decreased cholesterol levels in bodily tissues and fluids, as well as microcephaly, intellectual disability, and distinctive dysmorphic features.1,2 It is highly susceptible to free radical oxidation, giving rise to several oxysterols that may be involved in the pathogenesis of SLOS.1 7-DHC levels are increased in brain, liver, and serum in a rat model of SLOS induced by the DHCR7 inhibitor AY 9944 .1 7-DHC is a provitamin that is converted to vitamin D3 by ultraviolet-B (UVB) light in a human skin equivalent system and in isolated human skin samples.3,4
1.Xu, L., Liu, W., Sheflin, L.G., et al.Novel oxysterols observed in tissues and fluids of AY9944-treated rats: A model for Smith-Lemli-Opitz syndromeJ. Lipid Res.521810-1820(2011) 2.Xu, G., Salen, G., Shefer, S., et al.Reproducing abnormal cholesterol biosynthesis as seen in the Smith-Lemli-Opitz syndrome by inhibiting the conversion of 7-dehydrocholesterol to cholesterol in ratsJ. Clin. Invest.95(1)76-81(1995) 3.Lehmann, B., Genehr, T., Knuschke, P., et al.UVB-induced conversion of 7-dehydrocholesterol to 1α,25-dihydroxyvitamin D3 in an in vitro human skin equivalent modelJ. Invest. Dermatol.117(5)1179-1185(2001) 4.Chen, T.C., Chimeh, F., Lu, Z., et al.Factors that influence the cutaneous synthesis and dietary sources of vitamin DArch. Biochem. Biophys.460(2)213-217(2007)
| Cas No. | 434-16-2 | SDF | |
| 别名 | 7-去氢胆固醇 | ||
| 化学名 | cholesta-5,7-dien-3β-ol | ||
| Canonical SMILES | CC(C)CCC[C@@H](C)[C@H]1CC[C@@]2([H])C3=CC=C4C[C@@H](O)CC[C@]4(C)[C@@]3([H])CC[C@]12C | ||
| 分子式 | C27H44O | 分子量 | 384.64 |
| 溶解度 | Ethanol: 16.67 mg/mL (43.34 mM); DMSO: < 1 mg/mL (insoluble or slightly soluble) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.5998 mL | 12.9992 mL | 25.9983 mL |
| 5 mM | 0.52 mL | 2.5998 mL | 5.1997 mL |
| 10 mM | 0.26 mL | 1.2999 mL | 2.5998 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Targeting 7-Dehydrocholesterol Reductase Integrates Cholesterol Metabolism and IRF3 Activation to Eliminate Infection
Immunity 2020 Jan 14;52(1):109-122.e6.PMID:31882361DOI:10.1016/j.immuni.2019.11.015.
Recent work suggests that cholesterol metabolism impacts innate immune responses against infection. However, the key enzymes or the natural products and mechanisms involved are not well elucidated. Here, we have shown that upon DNA and RNA viral infection, macrophages reduced 7-Dehydrocholesterol reductase (DHCR7) expression. DHCR7 deficiency or treatment with the natural product 7-Dehydrocholesterol (7-DHC) could specifically promote phosphorylation of IRF3 (not TBK1) and enhance type I interferon (IFN-I) production in macrophages. We further elucidated that viral infection or 7-DHC treatment enhanced AKT3 expression and activation. AKT3 directly bound and phosphorylated IRF3 at Ser385, together with TBK1-induced phosphorylation of IRF3 Ser386, to achieve IRF3 dimerization. Deletion of DHCR7 and the DHCR7 inhibitors including AY9944 and the chemotherapy drug tamoxifen promoted clearance of Zika virus and multiple viruses in vitro or in vivo. Taken together, we propose that the DHCR7 inhibitors and 7-DHC are potential therapeutics against emerging or highly pathogenic viruses.
7-Dehydrocholesterol-derived oxysterols cause neurogenic defects in Smith-Lemli-Opitz syndrome
Elife 2022 Sep 16;11:e67141.PMID:36111785DOI:10.7554/eLife.67141.
Defective 3β-hydroxysterol-Δ7 -reductase (DHCR7) in the developmental disorder, Smith-Lemli-Opitz syndrome (SLOS), results in a deficiency in cholesterol and accumulation of its precursor, 7-Dehydrocholesterol (7-DHC). Here, we show that loss of DHCR7 causes accumulation of 7-DHC-derived oxysterol metabolites, premature neurogenesis from murine or human cortical neural precursors, and depletion of the cortical precursor pool, both in vitro and in vivo. We found that a major oxysterol, 3β,5α-dihydroxycholest-7-en-6-one (DHCEO), mediates these effects by initiating crosstalk between glucocorticoid receptor (GR) and neurotrophin receptor kinase TrkB. Either loss of DHCR7 or direct exposure to DHCEO causes hyperactivation of GR and TrkB and their downstream MEK-ERK-C/EBP signaling pathway in cortical neural precursors. Moreover, direct inhibition of GR activation with an antagonist or inhibition of DHCEO accumulation with antioxidants rescues the premature neurogenesis phenotype caused by the loss of DHCR7. These results suggest that GR could be a new therapeutic target against the neurological defects observed in SLOS.
7-Dehydrocholesterol Encapsulated Polymeric Nanoparticles As a Radiation-Responsive Sensitizer for Enhancing Radiation Therapy
Small 2022 Apr;18(17):e2200710.PMID:35304816DOI:10.1002/smll.202200710.
Therapeutics that can be activated by radiation in situ to enhance the efficacy of radiotherapy are highly desirable. Herein, 7-Dehydrocholesterol (7-DHC), a biosynthetic precursor of cholesterol, as a radiosensitizer, exploiting its ability to propagate the free radical chain reaction is explored. The studies show that 7-DHC can react with radiation-induced reactive oxygen species and in turn promote lipid peroxidation, double-strand breaks, and mitochondrial damage in cancer cells. For efficient delivery, 7-DHC is encapsulated into poly(lactic-co-glycolic acid) nanoparticles, forming 7-DHC@PLGA NPs. When tested in CT26 tumor bearing mice, 7-DHC@PLGA NPs significantly enhanced the efficacy of radiotherapy, causing complete tumor eradication in 30% of the treated animals. After treatment, 7-DHC is converted to cholesterol, causing no detectable side effects or hypercalcemia. 7-DHC@PLGA NPs represent a radiation-responsive sensitizer with great potential in clinical translation.
Ergosterol increases 7-Dehydrocholesterol, a cholesterol precursor, and decreases cholesterol in human HepG2 cells
Lipids 2022 Nov;57(6):303-311.PMID:36098332DOI:10.1002/lipd.12357.
Current treatment approaches for hyperlipidemia rely mainly on reducing the cholesterol level by inhibiting 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), which is involved in the presqualene pathway of cholesterol biosynthesis. Finding a compound that instead targets the postsqualene pathway could aid in the treatment of hyperlipidemia and synergistically reduce the cholesterol level when used in conjunction with HMGCR inhibitors. Ergosterol is a fungal sterol that is converted to brassicasterol by 7-Dehydrocholesterol reductase (DHCR7). DHCR7 is also a cholesterol biosynthesis enzyme, and thus ergosterol may cause the accumulation of 7-Dehydrocholesterol, a precursor of cholesterol and vitamin D3 , by a competitive effect. In this study, we examined the effect of ergosterol on the postsqualene pathway by quantifying cholesterol precursors and related sterols using gas chromatography-mass spectrometry and by conducting quantitative RT-PCR and western blot analysis for human HepG2 hepatoma cells. We found that ergosterol is converted into brassicasterol by the action of DHCR7 from HepG2 cells and that it induced the accumulation of cholesterol precursors (lathosterol, 7-Dehydrocholesterol, and desmosterol) and decreased the cholesterol level by altering the mRNA and protein levels of cholesterol biosynthesis enzymes (increase of sterol 8,7-isomerase [EBP] and decrease of DHCR7 and 24-dehydrocholesterol reductase [DHCR24]). These results demonstrate that ergosterol inhibits the postsqualene pathway and may be useful for the prevention of hyperlipidemia.
Engineered yeast for efficient de novo synthesis of 7-Dehydrocholesterol
Biotechnol Bioeng 2022 May;119(5):1278-1289.PMID:35128633DOI:10.1002/bit.28055.
The synthesis of vitamin D3 precursor 7-Dehydrocholesterol (7-DHC) by microbial fermentation has much attracted attention owing to its advantages of environmental protection. In this study, Saccharomyces cerevisiae was engineered for a de novo biosynthesis of 7-DHC. First, seven essential genes (six endogenous genes and one heterologous gene) were overexpressed, and the ROX1 gene (heme-dependent repressor of hypoxic genes) was knocked out. The resulting strain produced 82.6 mg/L 7-DHC from glucose. Then, we predicted five gene knockout targets for 7-DHC overproduction by the reconstruction of genome-scale metabolic model. GDH1 gene knockout increased the 7-DHC titer from 82.6 to 101.5 mg/L, and the specific growth rate of the ΔGDH1 mutant was also increased by 28%. Next, Ty1 transposon in S. cerevisiae was applied to increase the copies of the ERG1 gene and DHCR24 gene, resulting in a 120% increase in 7-DHC titer to 223.3 mg/L. Besides, to optimize the metabolic flux distribution, Clustered Regularly Interspaced Short Palindromic Repeats interference (CRISPRi) system was used to dynamically inhibit the competitive pathway, and the best binding site of ERG6 (delta (24)-sterol C-methyltransferase) promoter was screened out. The OD600 value of ERG6 regulated cells increased by 43% than knocking out ERG6 directly, and 7-DHC titer increased to 365.5 mg/L in a shake flask. Finally, the 7-DHC titer reached 1328 mg/L in 3-L bioreactor and the specific titer of 7-DHC reached up to 114.7 mg/g dry cell weight). Overall, this study constructed a yeast chassis for the highly efficient production of 7-DHC by systems metabolic engineering.