U 18666A
目录号 : GC15284
U18666A抑制3β羟基甾醇-Δ（24）还原酶 （DHCR24）活性，阻止胆固醇从晚期核内体和溶酶体外流。
Cas No.:3039-71-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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Cell experiment [1]: |
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Cell lines |
Rat Primery Atrocyte |
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Preparation method |
Cells were seeded at 1 × 104 cells/cm2 and harvested at 90% confluence. Cultured astrocytes were treated with 5 µg/ml U18666A for 24h. |
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Reaction Conditions |
1-5μg/ml, 24h |
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Applications |
U18666A (5μg/ml, 24 h) significant accumulation of cholesterol in astrocytes, promoted the expression of amyloid precursor protein, increased astrocyte beta-secretase, and then enhanced amyloid precursor protein metabolism and promoted the production of astrocyte beta amyloid protein. |
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Animal experiment [2]: |
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Animal models |
Sprague-Dawley rats |
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Preparation method |
Sprague-Dawley rat pups of both sexes were injected sub- cutaneously every other day beginning at one day of age with 10 mg/kg of U18666A in olive oil, approximately 70% develop dense nuclear cataracts between 15 and 25 days of age. The fiber plasma membrane of the control group and the treatment group were taken for follow-up experiments. |
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Dosage form |
10mg/kg, s.c., every other day,15-25 days |
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Applications |
U18666A results in the limited proteolytic breakdown of the main intrinstic protein of lens fiber cell plasma membrance, MP26, into MP23-24. |
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References: [1]. Yang H, Wang Y, Kar S. Effects of cholesterol transport inhibitor U18666A on APP metabolism in rat primary astrocytes. Glia. 2017 Nov;65(11):1728-1743. doi: 10.1002/glia.23191. Epub 2017 Jul 19. PMID: 28722194. [2]. Alcala J, Cenedella RJ, Katar M. Limited proteolysis of MP26 in lens fiber plasma membranes of the U18666A-induced cataract in rats. Curr Eye Res. 1985 Sep;4(9):1001-5. doi: 10.3109/02713689509000008. PMID: 3905265. |
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U18666A is a small molecule with cellular permeability and amphiphilism that inhibits 3β-hydroxysterol-Δ (24)-reductase (DHCR24) activity [1], thereby preventing cholesterol outflow from late endosomes and lysosomes [2]. U18666A has been used to model three diseases: Niemann-Pick disease, epilepsy and cataracts [3].
U18666A(0.1μg/μl) can inhibit intracellular transport and biosynthesis of cholesterol in Chinese hamster cells (CHO) [4]. In addition, U18666A (1 μg/ml,24h) can prevent the transfer of CD63/Lamp-3 from late endosomes to Weibel-palade bodiesin Human Umbilical Vein Endothelial Cells (HUVEC) [5].
U18666A(10mg/kg) given to Sprague-Dawley rats every other day beginning at 1 day of age resulted in dense nuclear cataract [6]. The rats were injected weekly with U18666A (10 mg/kg, s.c.) starting on day 1 after birth, and the rats were in a state of spontaneous seizures starting at sixth week [7].
References:
[1] Quan X, Chen X, Sun D, Xu B, Zhao L, Shi X, Liu H, Gao B, Lu X. The mechanism of the effect of U18666a on blocking the activity of 3β-hydroxysterol Δ-24-reductase (DHCR24): molecular dynamics simulation study and free energy analysis. J Mol Model. 2016 Feb;22(2):46. doi: 10.1007/s00894-016-2907-. Epub 2016 Jan 27. PMID: 26815033.
[2] Cenedella RJ. Cholesterol synthesis inhibitor U18666A and the role of sterol metabolism and trafficking in numerous pathophysiological processes. Lipids. 2009 Jun;44(6):477-87. doi: 10.1007/s11745-009-3305-7.Epub 2009 May 14. PMID: 19440746.
[3] Koh CH, Cheung NS. Cellular mechanism of U18666A-mediated apoptosis in cultured murine cortical neurons: bridging Niemann-Pick disease type C and Alzheimer's disease. Cell Signal. 2006 Nov;18(11):1844-53. doi: 10.1016/j.cellsig.2006.04.006. Epub 2006 May 7. PMID: 16797161.
[4] Liscum L, Faust JR. The intracellular transport of low density lipoprotein-derived cholesterol is inhibited in Chinese hamster ovary cells cultured with 3-beta-[2-(diethylamino) ethoxy] androst-5-en-17-one. J Biol Chem. 1989 Jul 15;264(20):11796-806. PMID: 274541.
[5] Kobayashi T, Vischer UM, Rosnoblet C, Lebrand C, Lindsay M, Parton RG, Kruithof EK, Gruenberg J. The tetraspanin CD63/lamp3 cycles between endocytic and secretory compartments in human endothelial cells. Mol Biol Cell. 2000 May;11(5):1829-43. doi: 10.1091/mbc.11.5.1829. PMID: 10793155; PMCID: PMC14887.
[6] Alcala J, Cenedella RJ, Katar M. Limited proteolysis of MP26 in lens fiber plasma membranes of the U18666A-induced cataract in rats. Curr Eye Res. 1985 Sep;4(9):1001-5. doi: 10.3109/02713689509000008. PMID: 3905265.
[7] Bierkamper GG, Cenedella RJ. Induction of chronic epileptiform activity in the rat by an inhibitor of cholesterol synthesis, U18666A. Brain Res. 1978 Jul 14;150(2):343-51. doi: 10.1016/0006-8993(78)90285-8. PMID: 678974.
U18666A是一种具有细胞渗透性和两亲性的小分子，可以抑制3β羟基甾醇-Δ（24）还原酶 （DHCR24）活性[1], 从而阻止胆固醇从晚期核内体和溶酶体外流[2]。U18666A已被用于建立尼曼-匹克疾病、癫痫病和白内障这三种疾病模型[3]。
在中国仓鼠细胞（CHO）中，U18666A(0.1μg/μl)可以抑制胆固醇的细胞内转运和生物合成[4]。另外，在人脐静脉内皮细胞(HUVEC)，U18666A（1 μg/ml,24h）可以阻止CD63/Lamp-3从晚期核内体到W-P小体（Weibel–Palade bodies）的转移[5]。
从出生第一天开始，每隔一天给予SD大鼠U18666A(10mg/kg)能够导致形成致密的核状白内障。从出生第一天开始，每周注射U18666A (10 mg/kg, 皮下注射)，从第6周开始，大鼠会处于自发性癫痫发作状态。
| Cas No. | 3039-71-2 | SDF | |
| 化学名 | (3S,8R,9S,10R,13S,14S)-3-(2-(diethylamino)ethoxy)-10,13-dimethyl-3,4,7,8,9,10,11,12,13,14,15,16-dodecahydro-1H-cyclopenta[a]phenanthren-17(2H)-one hydrochloride | ||
| Canonical SMILES | O=C1[C@]2(C)[C@@H](CC1)[C@H]3[C@H](CC2)[C@](CC[C@@H]4OCCN(CC)CC)(C)C(C4)=CC3.Cl | ||
| 分子式 | C25H41NO2.HCl | 分子量 | 424.07 |
| 溶解度 | 20mg/mL in ethanol, 10mg/mL in DMSO or DMF | 储存条件 | Store at -20°C,stored under nitrogen |
| 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 | 2.3581 mL | 11.7905 mL | 23.581 mL |
| 5 mM | 0.4716 mL | 2.3581 mL | 4.7162 mL |
| 10 mM | 0.2358 mL | 1.1791 mL | 2.3581 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。