Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Alisertib (MLN 8237) 是一种口服活性和选择性的Aurora A 激酶抑制剂,IC50值为 1.2 nM。它通过靶向白血病细胞中的AKT/mTOR/AMPK/p38途径诱导其凋亡和自噬,具有抗肿瘤活性。
规格 | 价格/CNY | 货期 | 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 * 10 mM (in DMSO) | ¥ 663 | 现货 |
产品描述 | Alisertib (MLN 8237) is a specific Aurora A inhibitor (IC50: 1.2 nM). The selectivity of Alisertib(MLN 8237) is >200-fold higher for Aurora A than Aurora B. |
靶点活性 | Aurora A:1.2 nM (cell free) |
体外活性 | Treatment of cultured MM cells with Alisertib (MLN8237) results in mitotic spindle abnormalities, mitotic accumulation, as well as inhibition of cell proliferation through apoptosis and senescence. In addition, MLN8237 up-regulates p53 and tumor suppressor genes p21 and p27. Combining MLN8237 with dexamethasone, doxorubicin, or bortezomib induces synergistic/additive anti-MM activity in vitro [1]. Alisertib inhibited AAK over ABK with a selectivity of more than 200-fold in cells. Alisertib inhibited proliferation of human tumor cell lines in vitro [2]. A T217D/W277E double mutant exhibits superior levels of resistance to MLN8237, with the I50 value increasing approximately 20-fold from 30 to 650 nM in the presence of TPX2 [3]. |
体内活性 | Tumor burden was significantly reduced and overall survival was significantly increased in animals treated with 30 mg/kg MLN8237 for 21 days. Induction of apoptosis and cell death by MLN8237 were confirmed in tumor cells excised from treated animals by TdT-mediated dUTP nick end labeling assay [1]. Alisertib produced a dose-dependent decrease in bipolar and aligned chromosomes in the HCT-116 xenograft model. Alisertib produced tumor growth inhibition in solid tumor xenograft models and regressions in in vivo lymphoma models. In addition, a dose of alisertib that caused tumor stasis, as measured by volume, resulted in a decrease in FLT uptake [2]. Nude mice bearing human tumor xenografts treated with a single oral dose of alisertib (20 mg/kg) displayed a phenotype consistent with inhibition of Aurora A [4]. |
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 |
化合物与蛋白结合的复合物 |
Crystal Structure of Ephrin A2 (EphA2) Receptor Protein Kinase with alisertib (MLN8237) |
分子量 | 518.92 |
分子式 | C27H20ClFN4O4 |
CAS No. | 1028486-01-2 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
DMSO: 50 mg/mL (96.35 mM)
H2O: < 1 mg/mL (insoluble or slightly soluble)
Ethanol: < 1 mg/mL (insoluble or slightly soluble)
可选溶剂 | 浓度 体积 质量 | 1 mg | 5 mg | 10 mg | 25 mg |
DMSO | 1 mM | 1.9271 mL | 9.6354 mL | 19.2708 mL | 48.177 mL |
5 mM | 0.3854 mL | 1.9271 mL | 3.8542 mL | 9.6354 mL | |
10 mM | 0.1927 mL | 0.9635 mL | 1.9271 mL | 4.8177 mL | |
20 mM | 0.0964 mL | 0.4818 mL | 0.9635 mL | 2.4088 mL | |
50 mM | 0.0385 mL | 0.1927 mL | 0.3854 mL | 0.9635 mL |
对于不同动物的给药剂量换算,您也可以参考 更多...
请在以下方框中输入您的动物实验信息后点击计算,可以得到母液配置方法和体内配方的制备方法: 比如您的给药剂量是10 mg/kg,每只动物体重20 g,给药体积100 μL,一共给药动物10 只,您使用的配方为5% DMSO+30% PEG300+5% Tween 80+60% ddH2O。那么您的工作液浓度为2 mg/mL。
母液配置方法:2 mg 药物溶于 50 μL DMSO (母液浓度为 40 mg/mL), 如您需要配置的浓度超过该产品的溶解度,请先与我们联系。
体内配方的制备方法:取 50 μL DMSO 主液,加入 300 μL PEG300, 混匀澄清,再加 50 μL Tween 80,混匀澄清,再加 600 μL ddH2O, 混匀澄清。
您可能有的问题的答案可以在抑制剂处理说明中找到,包括如何准备库存溶液,如何存储产品,以及基于细胞的分析和动物实验需要特别注意的问题。
Alisertib 1028486-01-2 Apoptosis Autophagy Cell Cycle/Checkpoint Chromatin/Epigenetic Aurora Kinase arrest myeloma MLN8237 cytotoxicity spindle inhibit mitotic cancer multiple MLN 8237 Inhibitor MLN-8237 cell-cycle 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 inhibitor