U 18666A |
رقم الكتالوجGC15284
One-Click Copy Product Info
|
U 18666A ، مثبط لنقل الكوليسترول داخل الخلايا ، يمنع تكاثر فيروس إيبولا ، وفيروس حمى الضنك ، وفيروس التهاب الكبد الوبائي البشري.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 3039-71-2
Sample solution is provided at 25 µL, 10mM.
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.
|
Cell experiment [1]: |
|
|
Cell lines |
Rat Primery Atrocyte |
|
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. |
|
Reaction Conditions |
1-5μg/ml, 24h |
|
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. |
|
Animal experiment [2]: |
|
|
Animal models |
Sprague-Dawley rats |
|
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. |
|
Dosage form |
10mg/kg, s.c., every other day,15-25 days |
|
Applications |
U18666A results in the limited proteolytic breakdown of the main intrinstic protein of lens fiber cell plasma membrance, MP26, into MP23-24. |
|
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. |
|
| Cas No. | 3039-71-2 | SDF | |
| Chemical Name | (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 | ||
| Formula | C25H41NO2.HCl | M.Wt | 424.07 |
| الذوبان | 20mg/mL in ethanol, 10mg/mL in DMSO or DMF | Storage | Store at -20°C,stored under nitrogen |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.3581 mL | 11.7905 mL | 23.581 mL |
| 5 mM | 471.6 μL | 2.3581 mL | 4.7162 mL |
| 10 mM | 235.8 μL | 1.1791 mL | 2.3581 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 28 reference(s) in Google Scholar.)