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受注：045-509-1970 |
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化学情報
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Synonyms | CI-1011, PD-148515 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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| 化学式 | C29H43NO4S |
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| 分子量 | 501.72 | CAS No. | 166518-60-1 | ||||||||
| Solubility (25°C)* | 体外 | DMSO | 100 mg/mL (199.31 mM) | ||||||||
| Ethanol | 16 mg/mL (31.89 mM) | ||||||||||
| Water | Insoluble | ||||||||||
| 体内 （毎回新しく調製した物を用意してください） |
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* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
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溶剤液（一定の濃度）を調合する
生物活性
| 製品説明 | Avasimibe inhibits ACAT with IC50 of 3.3 μM, also inhibits human P450 isoenzymes CYP2C9, CYP1A2 and CYP2C19 with IC50 of 2.9 μM, 13.9 μM and 26.5 μM, respectively. |
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| in vitro | Avasimibe at concentration of 1μg/mL causes reduction of Total cholesterol (TC) and Esterified cholesterol (EC) through inhibiting LDL binding and decreasing scavenger receptor numbers during foam cell formation in human monocyte-derived macrophages (HMMs). This compound at concentration of 2μg/mL enhances cholesterol efflux from established HMM foam cells preincubating with 10μg/ml LDL. [1] It inhibits Lipoprotein(a) accumulation in the culture media of primary monkey hepatocyte in a dose-dependent manner with 11.9% -31.3% inhibition, the change is mainly associated with decreased ApoA. [2] This chemical incubating at concentration of 10 nM, 1 μM, and 10 μM for 24 hours in HepG2 cells reduce ApoB secretion into media by 25%, 27%, and 43%, respectively. It decreases ApoB secretion by enhanced intracellular degradation of ApoB rather than decreased synthesis of ApoB. [3] The compound inhibits ACTC with IC50 of 3.3 μM in IC-21 macrophages with consideration of the total inhibitor concentration in the assay sample. [4] It inhibits human P450 isoenzymes CYP2C9, CYP1A2 and CYP2C19 with IC50 of 2.9 μM, 13.9 μM and 26.5 μM, respectively. [5] This inhibitor inhibits ACAT-1 expression and cholesterol ester synthesis in glioma cell lines. It inhibits the growth of the glioma cells by inducing cell cycle arrest and apoptosis due to caspase-8 and caspase-3 activation. [6] |
| in vivo | Avasimibe significantly reduces Lipoprotein(a) and total cholesterol levels in nine healthy male monkeys with a normal chow diet orally treated with CI-1011 at 30 mg/kg per day for 3 weeks, Lipoprotein(a) and total cholesterol levels reduce to 68 and 73% of control levels, respectively. This compound decreases total cholesterol mainly due to reduction of low density lipoprotein (LDL). [2] It decreases amyloid plaque load in the cortex and hippocampus and reduces the levels of insoluble Abeta40 and Abeta42 and C-terminal fragments of amyloid precursor protein (APP) in brain extracts in young human APP transgenic mice. This chemical reduces diffuse amyloid plaques by suppression of astrogliosis and enhanced microglial activation in aged human APP transgenic mice. [7] |
プロトコル(参考用のみ)
| キナーゼアッセイ | P450 Inhibition Studies | |
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| Pooled human liver microsomes (HLM) from at least 15 donors are used for all inhibition assays. For IC50 determinations, the substrate probes are used at their approximate in vitro Km values. All incubations are performed with 100 mM potassium phosphate buffer (pH 7.4) and 1 mM NADPH. For CYP1A2 inhibition study, incubations are performed in a total volume of 0.5 ml, in duplicates with 0.1 mg/ml HLM, 30 μM phenacetin, 1 mM NADPH, and in the presence of this compound (0, 0.3, 0.75, 1.5, 3, 7.5, 15, 30, and 40 μM in 50 mM) in a potassium phosphate buffer at pH 7.4. After preincubation at 37 °C for 7 min, NADPH is added to initiate the enzyme reaction. The reaction mixture is quenched with 500 μl of ice-cold 100 ng/ml paracetamol-D4/CH3CN after 25 min. The standards (4-acetamidophenol, singlet) and quality controls (triplicates for low, medium, and high) are prepared at room temperature. After mixing, 0.2 ml of the samples is transferred to another plate and submitted for LC/MS/MS analysis after centrifugation at 3000 rpm for 10 min. A Supelco Discovery Amide C16, 100 × 2.1 mm (5-μm particle size) column (Supelco, Bellefonte, PA) is used. The mobile phase is isocratic, 40:60 [acetonitrile/formic acid, 0.1% (v/v)] at 0.2 ml/min. | ||
| 細胞アッセイ | 細胞株 | primary human monocyte-derived macrophages |
| 濃度 | 1 μg/mL or 2 μg/mL | |
| 反応時間 | 48 hours | |
| 実験の流れ | For foam cell formation, the growth medium (RPMI medium containing 10% human serum) is aspirated and the BMMs are rinsed four times with RPMI medium, and then HMMs are exposed to RPMI medium containing bovine serum albumin (BSA, 0.2%) and (DMSO, 0.2%, vehicle for CI-1011) (control medium) with and without agacLDL (100 μg protein/ml) and this compound (1 μg/ml) for 48 hours. For cholesterol efflux experiments, HMMs are preincubated with ag-acLDL (100 μg protein/ml) for 24h, and then exposed to control RPMI medium with and without HDL (100 μg protein/ml), this compound (2 μg/ml) or HDL plus this compound (2 μg/ml) for 24–48 hours. Additionally, the appearance of [14C]FC in the medium is monitored by first preincubating HMMs with RPMI medium containing ag-acLDL (100 μg protein/ml) radiolabeled with [4-14C]FC (0.5 μCi/ml) in an ethanolic spritz (final concentration, 0.1%) for 24 h. The medium is removed, cells rinsed three times with RPMI medium, and then cells are exposed to control RPMI medium with and without this compound (1–10 μg/ml) for 4–48 h. At each time point, the medium is aspirated and centrifuged to pellet nonadherent cells. The appearance of [14C]FC in the medium is measured by liquid scintillation spectroscopy. Cellular lipids are extracted using hexane:isopropanol (3:2, v/v) for 1 h. The distribution of cellular radiolabeled cholesterol is measured by subjecting an aliquot of the cell extract and FC and EC standards to thin layer chromatography using petroleum ether:hexane:glacial acetic acid solvent system (85:15:2, v/v). The percent FC efflux is calculated as: medium [14C]FC dpm/ cell [14C] dpm×100. FC and TC mass are quantified by gas liquid chromatography using stigmasterol (1 mg/ml) as an internal standard. EC mass is calculated as the difference between TC and FC, and all values are normalized to cell protein. The MBC is defined as the lowest concentration that exhibited 99.9% or more reduction of the numbers of colonies compared with the cfu in the initial inoculum. |
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| 動物実験 | 動物モデル | male cynomolgus monkeys |
| 投薬量 | 30 mg/kg | |
| 投与方法 | Orally at a single dose per day for 3 weeks | |
参考
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カスタマーフィードバック
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, , Nature, 2016, 531(7596):651-5.
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Data from [Data independently produced by , , Oncogene, 2016, 35(50):6378-6388]
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Data from [Data independently produced by , , Nanomedicine, 2018, 14(8):2541-2550]
Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：
| Antioxidant interventions reduced cytokine-induced pyroptosis of peripheral MAIT cells in patients with HBV-related cirrhosis [ Hepatol Commun, 2025, 9(6)e0714] | PubMed: 40377492 |
| Specific activation of the integrated stress response uncovers regulation of central carbon metabolism and lipid droplet biogenesis [ Nat Commun, 2024, 15(1):8301] | PubMed: 39333061 |
| Stimulation of neutral lipid synthesis via viral growth factor signaling and ATP citrate lyase during vaccinia virus infection [ J Virol, 2024, 98(11):e0110324] | PubMed: 39475274 |
| An ACAT inhibitor suppresses SARS-CoV-2 replication and boosts antiviral T cell activity [ PLoS Pathog, 2023, 19(5):e1011323] | PubMed: 37134108 |
| Metabolic interventions improve HBV envelope-specific T-cell responses in patients with chronic hepatitis B [ Hepatol Int, 2023, 10.1007/s12072-023-10490-4] | PubMed: 36976426 |
| Cholesterol mediated ferroptosis suppression reveals essential roles of Coenzyme Q and squalene [ Commun Biol, 2023, 6(1):1108] | PubMed: 37914914 |
| Avasimibe Alleviates Disruption of the Airway Epithelial Barrier by Suppressing the Wnt/β-Catenin Signaling Pathway [ Front Pharmacol, 2022, 13:795934] | PubMed: 35222024 |
| Targeting cholesterol esterification as a novel immune checkpoint in viral infections and cancer [ UCL-, 2022, ] | PubMed: None |
| Targeting human Acyl-CoA:cholesterol acyltransferase as a dual viral and T cell metabolic checkpoint [ Nat Commun, 2021, 12(1):2814] | PubMed: 33990561 |
| Development of potent and selective inhibitors targeting the papain-like protease of SARS-CoV-2 [ Cell Chem Biol, 2021, S2451-9456(21)00213-0] | PubMed: 33979649 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。