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Avasimibe

现货
Catalog No.
A4318
ACAT抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 600.00
现货
10mg
¥ 500.00
现货
50mg
¥ 1,900.00
现货
200mg
¥ 5,400.00
现货

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Background

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.

Chemical Properties

StorageStore at -20°C
M.Wt501.72
Cas No.166518-60-1
FormulaC29H43NO4S
Solubility≥25.1 mg/mL in DMSO, ≥10.26 mg/mL in EtOH with ultrasonic, <2.55 mg/mL in H2O
Chemical Name[2,6-di(propan-2-yl)phenyl] N-[2-[2,4,6-tri(propan-2-yl)phenyl]acetyl]sulfamate
SDFDownload SDF
Canonical SMILESCC(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
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 [1]:

细胞系

HepG2细胞,大鼠肝细胞,THP-1细胞

溶解方法

该化合物在DMSO中的溶解度大于25.1 mg/mL。若获取更高浓度的溶液,可在37℃下孵育10分钟,随后在超声波浴中摇匀。-20℃以下可储存数月。

反应条件

0.2 μM-10 μM,24 h

应用

在THP-1细胞中,在顺序孵育系统中,avasimibe(0-0.2 μM)不影响细胞内胆固醇酯含量。在脂质负载过程(同时与avasimibe(0-0.2 μM)和乙酰低密度脂蛋白孵育)以浓度依赖性方式降低细胞胆固醇酯含量,其在0.2 μM时达到70%。Avasimibe(10 nM-10 μM)孵育24小时,以剂量依赖性方式显著降低从HepG2细胞分泌的载脂蛋白B 100。在HepG2细胞中,Aavasimibe(10 μM)孵育抑制载脂蛋白B及其他肝特异性蛋白的合成。Avasimibe(3 μM)将大鼠肝细胞总胆汁酸合成增加2.9倍。

动物实验 [1]:

动物模型

大鼠,小鼠

给药剂量

口服,1、10或30 mg/kg/day,两周

应用

在小鼠中,Avasimibe治疗显著减少含有游离胆固醇积累的病变数。在多次口服该化合物治疗的胆固醇喂养的大鼠中,Avasimibe显著降低血浆总胆固醇含量,增加HDL-胆固醇含量。在补充或不补充0.5%胆酸酯的高脂肪高胆固醇饮食饲养大鼠中,Avasimibe(在饮食中含0.01%,饲养一周)可将大鼠血浆胆固醇水平减少52%至71%。使用Avasimibe(3-30 mg/kg/天)治疗8-10周可降低血浆总胆固醇、VLDL-胆固醇、LDL-胆固醇和甘油三酯含量。在大鼠中,Avasimibe(3-30 mg/kg)将血浆胆固醇水平降低44%至66%。

注意事项

由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。

References:

[1]. Llaverías G, Laguna JC, Alegret M. Pharmacology of the ACAT inhibitor avasimibe (CI-1011). 2003 Spring;21(1):33-50.

生物活性

Description Avasimibe是一种可口服的ACAT抑制剂,IC50值为3.3 μM。
靶点 ACAT          
IC50 3.3 μM          

质量控制

化学结构

Avasimibe