Avasimibe (Synonyms: Cl-1011, PD-148515) |
Catalog No.GC10999
One-Click Copy Product Info
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Avasimibe is a selective and oral acyl coenzyme A:cholesterol acyltransferase (ACAT) inhibitor (IC50=12μmol/L).
Products are for research use only. Not for human use. We do not sell to patients.
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.
| Cell experiment [1]: | |
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Cell lines |
T24 cells |
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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. |
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Reaction Conditions |
0, 10 and 20μmol/L; 48h |
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Applications |
Avasimibe significantly inhibited the viability of T24 cells in a dose-dependent manner. |
| Animal experiment []: | |
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Animal models |
Female BALB/c-nu nude mice |
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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. |
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Dosage form |
30mg/kg/day for 18 days; i.p. |
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Applications |
Avasimibe treatment significantly inhibited the volume and weight of xenograft tumors in mice without changing the body weight of the mice. |
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References: |
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| Cas No. | 166518-60-1 | SDF | |
| Synonyms | Cl-1011, PD-148515 | ||
| Chemical Name | [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 | ||
| Formula | C29H43NO4S | M.Wt | 501.72 |
| Solubility | 100mg/ml in DMSO(Need ultrasonic), ≥ 10.26 mg/mL in EtOH with ultrasonic | Storage | Store at -20°C |
| 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. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9931 mL | 9.9657 mL | 19.9314 mL |
| 5 mM | 398.6 μL | 1.9931 mL | 3.9863 mL |
| 10 mM | 199.3 μL | 996.6 μL | 1.9931 mL |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
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Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)