Avasimibe
(Synonyms: 阿伐麦布,CI-1011; PD-148515) 目录号 : GC10999
Avasimibe是一种选择性口服酰基辅酶A：胆固醇酰基转移酶（ACAT）抑制剂（IC50=12μmol/L）。
Cas No.:166518-60-1
Sample solution is provided at 25 µL, 10mM.
Avasimibe is a selective and oral acyl coenzyme A:cholesterol acyltransferase (ACAT) inhibitor (IC50=12μmol/L)[1]. Avasimibe suppressed CYP2C9 (IC50=2.9μmol/L), CYP1A2 (IC50=13.9μmol/L), and CYP2C19 (IC50=26.5 μμmol/L)[2]. Avasimibe has been used in lipid-lowering research and anti-cancer research[3].
In vitro, Avasimibe demonstrated a dose-dependent suppression of U251 and U87 human glioblastoma cell proliferation with IC50 values of 20.29μmol/L and 28.27μmol/L, respectively after 48 hours of treatment[4]. When exposed to Avasimibe for 48 hours at 30μmol/L, U251 and U87 human glioblastoma cells showed decreased DNA synthesis together with suppressed cell clone formation[4]. The prostate cancer cells PC-3 and DU 145 showed decreased viability after receiving Avasimibe treatment at 20μmol/L concentration over 72 hours, which led to decreased sterol O-acyltransferase (SOAT) expression levels[5]. Avasimibe treatment at 20μmol/L for 48 hours reduced T24 cell proliferation and migration while increasing intracellular reactive oxygen species (ROS) production, accompanied by the upregulation of the expressions of ROS metabolism-related proteins SOD2 and catalase[6].
In vivo, Avasimibe treatment (25mg/kg/day; 28 days) via oral administration to miniature pigs fed a fat- and cholesterol-containing diet significantly decreased the secretion of hepatic apolipoprotein (apo) B containing lipoproteins into plasma[7]. In the asthma mouse model, intratracheal injection of Avasimibe at 20mg/kg significantly reduced the production of IL-4 and IL-5 in bronchoalveolar lavage fluid (BALF) and total IgE in serum, resulting in reduced mucus secretion in the airway epithelium of mice, decreased goblet cells and basal cells[8].
References:
[1] Llaverías G, Laguna J C, Alegret M. Pharmacology of the AC AT Inhibitor Avasimibe (CI‐1011)[J]. Cardiovascular drug reviews, 2003, 21(1): 33-50.
[2] Sahi J, Stern R H, Milad M A, et al. Effects of avasimibe on cytochrome P450 2C9 expression in vitro and in vivo[J]. Drug metabolism and disposition, 2004, 32(12): 1370-1376.
[3] Tardif J C, Grégoire J, L’Allier P L, et al. Effects of the acyl coenzyme A: cholesterol acyltransferase inhibitor avasimibe on human atherosclerotic lesions[J]. Circulation, 2004, 110(21): 3372-3377.
[4] Liu J, Fu W, Zheng X, et al. Avasimibe exerts anticancer effects on human glioblastoma cells via inducing cell apoptosis and cell cycle arrest[J]. Acta Pharmacologica Sinica, 2021, 42(1): 97-107.
[5] Xiong K, Wang G, Peng T, et al. The cholesterol esterification inhibitor avasimibe suppresses tumour proliferation and metastasis via the E2F-1 signalling pathway in prostate cancer[J]. Cancer Cell International, 2021, 21: 1-13.
[6] Peng T, Xiong K, He Z, et al. Acyl-coenzyme A: cholesterol acyltransferase inhibitor avasimibe suppresses tumorigenesis and induces G1-phase cell-cycle arrest by activating PPARγ signaling pathway in bladder cancer[J]. Journal of Cancer, 2024, 15(2): 370.
[7] Burnett J R, Telford D E, Barrett P H R, et al. The ACAT inhibitor avasimibe increases the fractional clearance rate of postprandial triglyceride-rich lipoproteins in miniature pigs[J]. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids, 2005, 1738(1-3): 10-18.
[8] Zhou Z, Liang S, Zhou Z, et al. Avasimibe alleviates disruption of the airway epithelial barrier by suppressing the wnt/β-catenin signaling pathway[J]. Frontiers in Pharmacology, 2022, 13: 795934.
Avasimibe是一种选择性口服酰基辅酶A：胆固醇酰基转移酶（ACAT）抑制剂（IC50=12μmol/L）[1]。Avasimibe对CYP2C9（IC50=2.9μmol/L）、CYP1A2（IC50=13.9μmol/L）和CYP2C19（IC50=26.5μmol/L）具有抑制作用[2]。Avasimibe已被应用于降脂研究和抗癌研究[3]。
在体外，Avasimibe处理48小时后能剂量依赖性抑制U251和U87人胶质母细胞瘤细胞的增殖，IC50值分别为20.29μmol/L和28.27μmol/L[4]。当以30μmol/L浓度的Avasimibe处理48小时后，U251和U87细胞不仅DNA合成减少，细胞克隆形成能力也受到抑制[4]。在前列腺癌细胞PC-3和DU 145中，20μmol/L浓度的Avasimibe处理72小时可降低细胞活力，同时下调固醇O-酰基转移酶（SOAT）表达水平[5]。20μmol/L浓度的Avasimibe处理T24细胞48小时能抑制细胞增殖和迁移，同时增加细胞内活性氧（ROS）生成，并上调ROS代谢相关蛋白SOD2和过氧化氢酶的表达[6]。
在体内，高脂高胆固醇饮食的小型猪在连续28天口服25mg/kg/day剂量的Avasimibe后，肝脏分泌含载脂蛋白B（apoB）的脂蛋白进入血浆的量显著减少[7]。在哮喘小鼠模型中，20mg/kg剂量的Avasimibe经气管内注射可显著降低支气管肺泡灌洗液（BALF）中IL-4、IL-5水平及血清总IgE含量，减少小鼠气道上皮黏液分泌，同时降低杯状细胞和基底细胞数量[8]。
| Cell experiment [1]: | |
Cell lines | T24 cells |
Preparation Method | The T24 cells grew in RPMI-1640 medium with 10% fetal bovine serum inside a 37ºC incubator under 5% CO2 conditions. Each well of the 96-well plate received 200μL of medium containing 3,000 cells before being treated with Avasimibe at concentrations of 0, 10 and 20μmol/L. Following a treatment period of 48 hours with Avasimibe, add 20μL of 5mg/mL MTT solution. The medium was taken out of the 96-well plate following a 4-hour incubation and then 150μL of DMSO was added to each well. Place the shaker device in operation for 10 minutes with gentle motion until the formazan precipitate fully dissolves. The absorbance of each well at 570nm was measured using a microplate reader in order to determine cell viability. |
Reaction Conditions | 0, 10 and 20μmol/L; 48h |
Applications | Avasimibe significantly inhibited the viability of T24 cells in a dose-dependent manner. |
| Animal experiment []: | |
Animal models | Female BALB/c-nu nude mice |
Preparation Method | The experiment involved six-week-old female BALB/c-nu nude mice with a body weight range of 15-18g. Implant U87 cells at a concentration of 1×107cells per mouse into the right flank area of each mouse. After 14 days, the mice with a minimum tumor volume of 100mm3 were randomly assigned to three experimental groups of six mice each. The mice received daily intraperitoneal injections with 30mg/kg Avasimibe or no treatment for a period of 18 days. The tumor volume was measured using a Vernier caliper and calculated according to the following modified ellipsoid formula: tumor volume (mm3)=(length)×(width)2×0.5. The experiment concluded by sacrificing all mice and collecting their tumor tissues for weighing and photographic documentation. |
Dosage form | 30mg/kg/day for 18 days; i.p. |
Applications | Avasimibe treatment significantly inhibited the volume and weight of xenograft tumors in mice without changing the body weight of the mice. |
References: | |
| 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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| 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 |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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