Lanosterol
(Synonyms: 羊毛甾醇) 目录号 : GC19477
Lanosterol是胆固醇生物合成过程中的一种三萜类中间体，能够诱导HMG CoA还原酶的泛素化和降解。
Cas No.:79-63-0
Sample solution is provided at 25 µL, 10mM.
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Lanosterol is a triterpenoid intermediate in the biosynthesis of cholesterol, which can induce the ubiquitination and degradation of HMG CoA reductase [1]. Defects in Lanosterol can lead to various diseases, including the formation of cataracts [2]. Lanosterol can inhibit the aggregation and toxicity of misfolded proteins related to neurodegenerative diseases [3].
In vitro, treatment with Lanosterol (5μM; 24h) significantly inhibited the cell death of dopaminergic neurons induced by 1-methyl-4-phenylpyridine (MPP+), increased autophagy in neurons, and induced uncoupling of mitochondria in neurons [4]. Treatment with Lanosterol (20μM; 48h) increased the endogenous level of 20S proteasome in A549 and Cos-7 cell lines, promoted proteasome degradation of misfolded proteins, and reduced the aggregation of mutant GFP-Δ9CAT protein [5].
In vivo, oral administration of Lanosterol (1 or 2%, w/w; 10 weeks) significantly inhibited the formation of abnormal crypts and multiple crypts in rat colon induced by nitrosomethane (AOM), and 2% Lanosterol significantly increased serum high-density lipoprotein and cholesterol levels [6]. Local ocular administration of Lanosterol (25mM; 6 weeks) improved the clarity of canine lenses and alleviated cataracts [7].
References:
[1] Chen N, et al. Biosynthetic Mechanism of Lanosterol: Cyclization. Angew Chem Int Ed Engl. 2015 Jul 20;54(30):8693-6.
[2] Zhao L, Chen X J, Zhu J, et al. Lanosterol reverses protein aggregation in cataracts[J]. Nature, 2015, 523(7562): 607-611.
[3] Upadhyay A, Amanullah A, Mishra R, et al. Lanosterol suppresses the aggregation and cytotoxicity of misfolded proteins linked with neurodegenerative diseases[J]. Molecular neurobiology, 2018, 55(2): 1169-1182.
[4] Lim L, Jackson-Lewis V, Wong L C, et al. Lanosterol induces mitochondrial uncoupling and protects dopaminergic neurons from cell death in a model for Parkinson's disease[J]. Cell Death & Differentiation, 2012, 19(3): 416-427.
[5] Kinger S, Jagtap Y A, Dubey A R, et al. Lanosterol elevates cytoprotective response through induced-proteasomal degradation of aberrant proteins[J]. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 2024, 1871(2): 119631.
[6] Rao C V, Newmark H L, Reddy B S. Chemopreventive effect of farnesol and lanosterol on colon carcinogenesis[J]. Cancer detection and prevention, 2002, 26(6): 419-425.
[7] Zhao L, Chen X J, Zhu J, et al. Lanosterol reverses protein aggregation in cataracts[J]. Nature, 2015, 523(7562): 607-611.
Lanosterol是胆固醇生物合成过程中的一种三萜类中间体，能够诱导HMG CoA还原酶的泛素化和降解 [1]。Lanosterol的缺陷会导致多种疾病，其中包括白内障的形成 [2]。Lanosterol能够抑制与神经退行性疾病相关的错误折叠蛋白质的聚集和毒性作用 [3]。
在体外，Lanosterol（5μM; 24h）处理显著抑制了1-甲基-4-苯基吡啶（MPP+）诱导的多巴胺能神经元的细胞死亡，增加了神经元的自噬并诱导神经元中线粒体的解偶联 [4]。Lanosterol（20μM; 48h）处理增加了A549和Cos-7细胞系中20S蛋白酶体的内源性水平，促进错误折叠蛋白质的蛋白酶体降解，并减少了突变型GFP-Δ9CAT蛋白的聚集 [5]。
在体内，Lanosterol（1 or 2%, w/w; 10 weeks）通过口服治疗显著抑制了氮氧甲烷（AOM）诱导的大鼠结肠异常隐窝病灶（ACF）以及多隐窝病灶的形成，2%的Lanosterol显著增加了血清高密度脂蛋白和胆固醇水平 [6]。Lanosterol（25mM; 6 weeks）通过眼局部给药治疗提高了犬类晶状体的清晰度，缓解已形成的白内障 [7]。
| Cell experiment [1]: | |
Cell lines | Rat hippocampal neuron cells |
Preparation Method | Neurons were plated on a wax-dotted coverslip coated with 1mg/ml of poly-D-lysine. Two hours after plating, when neurons had attached, the coverslips were flipped into a six-well plate containing a glia feeder layer. Hippocampal neuron cultures plated on 12mm coverslips were treated for 24h with 10μM 1-methyl-4-phenylpyridinium (MPP+) with or without 5μM cholesterol or 5μM Lanosterol liposome. Cells were washed three times with PBS, then fixed with 4% paraformaldehyde for 20min, followed by permeabilization and blocking in 5% fetal bovine serum in 0.1% TritonX-100 for 30min. TUJ1-positive and TH-positive cells were counted with an Olympus fluorescence microscope with FITC and TRITC filter sets. Every neuron on the 12mm coverslip was counted. |
Reaction Conditions | 5μM; 24h |
Applications | Lanosterol treatment significantly inhibited the cell death of dopaminergic neurons induced by MPP+. |
| Animal experiment [2]: | |
Animal models | Weanling male F344 rats (aberrant crypt foci (ACF) model) |
Preparation Method | At 7 weeks of age, groups of rats were fed the modified AIN-76A (control) or experimental diets containing 1.5% farnesol, or 1 or 2% Lanosterol. At 8 weeks of age, all animals except the vehicle-treated rats received azoxymethane (AOM) s.c. once weekly for 2 weeks at a dose rate of 15mg/kg body weight per week. Animals intended for vehicle treatment were given an equal volume of normal saline. The rats were continued on control and experimental diets until the termination of the study when they were 17 weeks of age. All animals were sacrificed by CO2 euthanasia. Blood samples were collected from individual rats (AOM-treated) to analyze for cholesterol and High-density lipoprotein. |
Dosage form | 1 or 2%, w/w; 10 weeks |
Applications | Lanosterol treatment significantly inhibited the formation of multiple recessive lesions in rats, and 2% of wool sterol significantly increased the levels of serum high-density lipoprotein and cholesterol. |
References: | |
| Cas No. | 79-63-0 | SDF | |
| 别名 | 羊毛甾醇 | ||
| 化学名 | Lanosta-8,24-dien-3-ol, (3β)- | ||
| Canonical SMILES | C[C@]12C3=C(CC[C@@]1([C@]([C@H](C)CC/C=C(C)/C)([H])CC2)C)[C@@]4([C@@](C(C)([C@@H](O)CC4)C)([H])CC3)C | ||
| 分子式 | C₃₀H₅₀O | 分子量 | 426.72 |
| 溶解度 | DMF: 3 mg/ml,Ethanol : 6 mg/ml | 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 | 2.3435 mL | 11.7173 mL | 23.4346 mL |
| 5 mM | 468.7 μL | 2.3435 mL | 4.6869 mL |
| 10 mM | 234.3 μL | 1.1717 mL | 2.3435 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。
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Quality Control & SDS
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- Purity: >98.00%
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