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Alisertib (MLN 8237) 是一种 Aurora A 激酶抑制剂 (IC50=1.2 nM),具有口服活性和选择性。Alisertib 具有抗肿瘤活性,可以诱导细胞凋亡和自噬,诱导细胞周期阻滞。
Alisertib (MLN 8237) 是一种 Aurora A 激酶抑制剂 (IC50=1.2 nM),具有口服活性和选择性。Alisertib 具有抗肿瘤活性,可以诱导细胞凋亡和自噬,诱导细胞周期阻滞。
规格 | 价格 | 库存 | 数量 |
---|---|---|---|
1 mg | ¥ 248 | 现货 | |
5 mg | ¥ 578 | 现货 | |
10 mg | ¥ 813 | 现货 | |
25 mg | ¥ 1,490 | 现货 | |
50 mg | ¥ 2,450 | 现货 | |
100 mg | ¥ 3,180 | 现货 | |
200 mg | ¥ 5,120 | 现货 | |
500 mg | ¥ 7,890 | 现货 | |
1 mL x 10 mM (in DMSO) | ¥ 663 | 现货 |
产品描述 | Alisertib (MLN 8237) is an Aurora A kinase inhibitor (IC50=1.2 nM) with oral activity and selectivity. Alisertib has antitumor activity, induces apoptosis and autophagy, and induces cell cycle arrest. |
靶点活性 | Aurora A:1.2 nM (cell free) |
体外活性 | 方法:从 MM 患者获得的一组 MM 细胞系和肿瘤细胞用 Alisertib (0.0001-4 µM) 处理 48-72 h,使用 MTT assay 检测细胞活力。 结果:尽管 Alisertib 的细胞毒性活性早在暴露于低于 0.1 µM/L 的 24-48 h 就在几种细胞系中检测到了,但在所有细胞系中,在 72 h 时都发生了更强烈的细胞毒性。[1] 方法:人结直肠癌细胞 HCT-116 用 Alisertib (0.05-1 µmol/L) 处理 24-48 h,使用 Flow cytometry 检测细胞周期。 结果:在浓度为 0.050 µmol/L 时,在 24 和 48 h 时,G2/M 期的细胞增加,表型与 Aurora A 抑制一致。在 0.250 和 1.000 µmol/L 的较高浓度下,Alisertib 处理的细胞显示出与 Aurora B 抑制一致的表型,显示 8N DNA 含量的细胞数量增加。[2] |
体内活性 | 方法:为研究抗肿瘤活性,将 Alisertib (7.5-30 mg/kg,10% 2-hydroxypropyl-β-cyclodextrin/1% sodium bicarbonate) 口服给药给携带 MM1.S 异种移植物的 SCID 小鼠,每天一次,持续二十一天。 结果:用 30 mg/kg Alisertib 治疗的动物的肿瘤负荷显著降低。与对照相比,15 mg/kg (TGI=42%) 和 30 mg/kg (TGI=80%) 处理的动物的 TGI 显著。[1] |
激酶实验 | Recombinant murine Aurora A and Aurora B protein were expressed in Sf9 cells and purified with GST affinity chromatography. The peptide substrate for Aurora A was conjugated with biotin (Biotin-GLRRASLG). Aurora A kinase (5 nM) was assayed in 50 mM Hepes (pH 7.5)/10 mM MgCl2/5 mM DTT/0.05% Tween 20/2 μM peptide substrate/3.3 μCi/ml [γ-33P]ATP at 2 μM by using Image FlashPlates. Aurora B kinase (2 nM) was assayed with 10 μM biotinylated peptide Biotin-TKQTARKSTGGKAPR in 50 mM Tricine (pH 8.0)/2.5 mM MgCl2/5 mM DTT/10% glycerol/2% BSA/40 μCi/ml [γ-33P]ATP at 250 μM. The conditions for all other in vitro kinase assays are available upon request. MLN8054 was run in a 226 kinase screen at a 1 μM compound concentration with an ATP concentration of 10 μM for all assays [2]. |
细胞实验 | HCT-116 colorectal carcinoma cells were plated on 6-well dishes (2 × 10^5 per well) and propagated in McCoy's 5A media supplemented with 10% FBS. After 18 hours, alisertib at a final concentration of 0.050, 0.250, or 1.000 μmol/L was added, and the cells were grown for an additional 24 hours. Cells treated with dimethyl sulfoxide (DMSO; 0.2%) served as the untreated vehicle control. The cells were harvested with trypsin EDTA 1×, washed once with PBS, fixed in 70% ethanol, and stored at 4°C for 1 hour. The cells were resuspended in propidium iodide (1:40) and RNAse A (1:5,000) in PBS for 30 minutes at 4°C. Cell-cycle distributions were determined by measuring DNA content using flow cytometry, and samples were analyzed using Winlist 5.0 software [2]. |
动物实验 | Mice were irradiated (200 cGy), and then 5 × 106 MM1.S cells were inoculated subcutaneously in the right flank. When tumor growth was measurable (~ 2 weeks after the injection), mice were assigned into 4 groups (10 mice each) receiving vehicle orally (100 μL of 10% 2-hydroxypropyl-β-cyclodextrin/1% sodium bicarbonate) or MLN8237 (7.5 mg/kg, 15 mg/kg, and 30 mg/kg in a final formulation in 10% 2-hydroxypropyl-β-cyclodextrin/1% sodium bicarbonate) for 21 consecutive days. The maximal tolerated dose of MLN8237 in most mouse strains (continuous dosing for 21 days) is approximately 20 mg/kg twice a day (40 mg/kg per day). Tumor volumes were measured by a Vernier caliper every alternate day and calculated using the following formula: length × width2 × 0.5. Tumor growth inhibition (TGI) was calculated using the formula (Δcontrol average volume ? Δtreated average volume) × 100/(Δcontrol average volume). Mice were killed at the end of the treatment, 2 hours after the last treatment, or when tumor reached 2 cm^3; tumors were immediately collected from mice and evaluated for induction of apoptosis and cell death by TdT-mediated dUTP nick end labeling (TUNEL) assay [1]. |
别名 | MLN 8237, 4-[[9-氯-7-(2-氟-6-甲氧基苯基)-5H-嘧啶并[5,4-D][2]苯并氮杂卓-2-基]氨基]-2-甲氧基苯甲酸 |
分子量 | 518.92 |
分子式 | C27H20ClFN4O4 |
CAS No. | 1028486-01-2 |
Smiles | COc1cc(Nc2ncc3CN=C(c4cc(Cl)ccc4-c3n2)c2c(F)cccc2OC)ccc1C(O)=O |
密度 | 1.438 g/cm3 |
存储 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. | |||||||||||||||||||||||||||||||||||
溶解度信息 | 10% DMSO+40% PEG300+5% Tween 80+45% Saline: 5 mg/mL (9.64 mM), Suspension. Please add co-solvents sequentially, clarifying the solution as much as possible before adding the next one. Dissolve by heating and/or sonication if necessary. Working solution is recommended to be prepared and used immediately. DMSO: 50 mg/mL (96.35 mM) H2O: < 1 mg/mL (insoluble or slightly soluble) Ethanol: < 1 mg/mL (insoluble or slightly soluble) | |||||||||||||||||||||||||||||||||||
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