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Alisertib

Alisertib

产品编号 T2241   CAS 1028486-01-2
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

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途径诱导其凋亡自噬,具有抗肿瘤活性。

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Alisertib Chemical Structure
Alisertib, CAS 1028486-01-2
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
其他形式的 Alisertib:
产品目录号及名称: Alisertib (T2241)
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选择批次  
纯度: 100%
纯度: 99.82%
纯度: 99.59%
纯度: 98.92%
纯度: 98.91%
纯度: 98.73%
纯度: 98.31%
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生物活性
化学信息
存储 & 溶解度
参考文献
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

T2241_1

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

存储

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

溶解度

DMSO: 50 mg/mL (96.35 mM)

H2O: < 1 mg/mL (insoluble or slightly soluble)

Ethanol: < 1 mg/mL (insoluble or slightly soluble)

溶液配制表

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

计算器

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稀释计算器
配液计算器
分子量计算器
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参考文献

1. Güllü G, et al. A novel Aurora-A kinase inhibitor MLN8237 induces cytotoxicity and cell-cycle arrest in multiple myeloma Blood June 24, 2010 vol. 115 no. 25 5202-5213 2. Manfredi MG, et al. Characterization of Alisertib (MLN8237), an investigational small-molecule inhibitor of aurora A kinase using novel in vivo pharmacodynamic assays. Clin Cancer Res. 2011 Dec 15;17(24):7614-24. 3. Sloane DA, et al. Drug-Resistant Aurora A Mutants for Cellular Target Validation of the Small Molecule Kinase Inhibitors MLN8054 and MLN8237. ACS Chem Biol. 2010 Jun 18;5(6):563-76. 4. Sells TB, et al. MLN8054 and Alisertib (MLN8237): Discovery of Selective Oral Aurora A Inhibitors. ACS Med Chem Lett. 2015 Apr 22;6(6):630-4. 5. Huang Y, Mu K, Teng X, et al. Identification and mechanistic analysis of an inhibitor of the CorC Mg2+ transporter[J]. iScience. 2021

文献引用

1. Sun Y, Gao Y, Chen J, et al. CREBBP cooperates with the cell cycle machinery to attenuate chidamide sensitivity in relapsed/refractory diffuse large B-cell lymphoma. Cancer Letters. 2021 2. Qi J, Gao X, Zhong X, et al. Selective inhibition of Aurora A and B kinases effectively induces cell cycle arrest in t(8;21) acute myeloid leukemia. Biomedicine & Pharmacotherapy. 2019, 117: 109113. 3. Wang D, Wang Y, Di X, et al.Cortical tension drug screen links mitotic spindle integrity to Rho pathway.Current Biology.2023
C6 Ceramide Diallyl Trisulfide Rigosertib sodium Dutasteride Clofarabine Metronidazole Terrestrosin D Pectolinarin

相关化合物库

该产品包含在如下化合物库中:
高选择性抑制剂库 抗癌活性化合物库 抗癌药物库 抗癌临床化合物库 自噬库 表观遗传库 含氟化合物库 抗乳腺癌化合物库 细胞周期化合物库 抗癌化合物库

剂量换算

对于不同动物的给药剂量换算,您也可以参考 更多...

体内实验配液计算器

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。

第一步:请输入动物实验的基本信息
剂量
mg/kg
每只动物体重
g
给药体积
μL
动物数量
第二步:请输入动物体内配方组成,不同的产品配方组成不同,如有配方需求,可先联系我们提供正确的体内配方。
% DMSO
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% Tween 80
% ddH2O
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技术支持

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。

Keywords

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

 

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