Avasimibe
(Synonyms: 阿伐麦布,CI-1011; PD-148515) 目录号 : GC10999
An ACAT inhibitor
Cas No.:166518-60-1
Sample solution is provided at 25 µL, 10mM.
Avasimibe is an orally bioavailable inhibitor of the acyl coenzyme A: cholesterol acyltransferase (ACAT) with IC50 value of 60nM [1].
Avasimibe is developed from a strategy to design ACAT inhibitors with improved bioavailability. It also has solution stability at acidic pH. In the in vitro assay, the IC50 value is dependent on the concentration of microsomes, the amount of membrane available for adsorption as well as the presence of BSA. The treatment of avasimibe during the process of lipid loading causes a concentration-dependent reduction in cellular cholesteryl ester content. This reduction is not accompanied by the accumulation of intracellular free cholesterol, indicating a better safety profile for avasimibe than other ACAT inhibitors. Avasimibe can also reduce the synthesis and secretion of Apo B 100 (a component of VLDL) in HepG2 cells. In addition, avasimibe can increase the total bile acid synthesis in rat hepatocytes at the concentration of 3μM [1].
Apart from the antiatherosclerotic efficacy, avasimibe is also found to take participate in the modulation of APP trafficking. It can delay and reduce the maturation of APP, limiting the availability of APP holoprotein for Aβ-generatiion [2].
References:
[1] Llaverías G, Laguna JC, Alegret M. Pharmacology of the ACAT inhibitor avasimibe (CI-1011). 2003 Spring;21(1):33-50.
[2] Huttunen HJ, Peach C, Bhattacharyya R, Barren C, Pettingell W, Hutter-Paier B, Windisch M, Berezovska O, Kovacs DM. Inhibition of acyl-coenzyme A: cholesterol acyl transferase modulates amyloid precursor protein trafficking in the early secretory pathway. FASEB J. 2009 Nov;23(11):3819-28.
| Cell experiment [1]: | |
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Cell lines |
HepG2 cells; rat hepatocytes; THP-1 cells |
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Preparation method |
The solubility of this compound in DMSO is >25.1mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
0.2 μM-10 μM; 24 h |
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Applications |
In THP-1 cells, avasimibe (0-0.2 μM) did not reduce intracellular cholesteryl ester content in a sequential incubation system. Incubations with avasimibe (0-0.2 μM) during the process of lipid loading (simultaneous incubation with avasimibe and acetyl-LDL) caused a concentration-dependent reduction in cellular cholesteryl ester content, which reached 70% at 0.2 μM. Incubation with avasimibe (10 nM - 10 μM) for 24 h caused a significant dose-dependent reduction in apo B 100 secretion from HepG2 cells. Overnight incubation of HepG2 cells with 10 μM avasimibe suppressed apo B synthesis, as well as the synthesis of other hepa-to-specific proteins. Avasimibe (3 μM) caused a 2.9-fold increase in total bile acid synthesis in rat hepatocytes. |
| Animal experiment [1]: | |
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Animal models |
Rats, Mice |
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Dosage form |
Oral; 1, 10, or 30 mg/kg/day; 2 weeks |
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Application |
In mice, treatment with avasimibe significantly reduced the number of lesions containing accumulations of free cholesterol. In cholesterol-fed rats treated with multiple oral doses of the compound, avasimibe significantly reduced plasma total cholesterol and increased HDL-cholesterol. Avasimibe (0.01% in the diet for 1 week) reduced plasma cholesterol levels in rats fed a high fat-high cholesterol diet, supplemented or not with 0.5% cholate, by 52 to 71%. Treatment with avasimibe (3–30 mg/kg/day) for 8–10 weeks lowered plasma total cholesterol, VLDL-cholesterol, LDL-cholesterol, and triglyceride levels.In chow-fed rats, avasimibe (3–30 mg/kg) reduced plasma cholesterol levels by 44 to 66%. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Llaverías G, Laguna JC, Alegret M. Pharmacology of the ACAT inhibitor avasimibe (CI-1011). 2003 Spring;21(1):33-50. | |
| Cas No. | 166518-60-1 | SDF | |
| 别名 | 阿伐麦布,CI-1011; PD-148515 | ||
| 化学名 | [2,6-di(propan-2-yl)phenyl] N-[2-[2,4,6-tri(propan-2-yl)phenyl]acetyl]sulfamate | ||
| Canonical SMILES | CC(C)C1=C(C(=CC=C1)C(C)C)OS(=O)(=O)NC(=O)CC2=C(C=C(C=C2C(C)C)C(C)C)C(C)C | ||
| 分子式 | C29H43NO4S | 分子量 | 501.72 |
| 溶解度 | ≥ 25.1 mg/mL in DMSO, ≥ 10.26 mg/mL in EtOH with ultrasonic | 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 | 1.9931 mL | 9.9657 mL | 19.9314 mL |
| 5 mM | 0.3986 mL | 1.9931 mL | 3.9863 mL |
| 10 mM | 0.1993 mL | 0.9966 mL | 1.9931 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。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet