MLN8237 (Alisertib)
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
MLN8237（alisertib）是一种可口服的、有效的Aurora A激酶（AAK）小分子抑制剂。Aurora A激酶在多种类型的肿瘤中是过表达的，与肿瘤的发生和发展相关。MLN8237是从其前体MLN8054发展而来，以便最大限度地减少MLN8054的苯并二氮杂样作用。MLN8237的抑制作用是ATP竞争性的、可逆的和AAK特异性的，抑制常数Ki值为0.43 nmol/L。由于其在体外和体内的广泛抗肿瘤活性，MLN8237正用于治疗晚期恶性肿瘤的研究。
参考文献：
E. Claire Dees, Roger B. Cohen, Margaret von Mehren, Thomas E. Stinchcombe, Hua Liu, Karthik Venkatakrishnan, Mark Manfredi, Howard Fingert, Howard A. Burris III, and Jeffrey R. Infante. Phase I study of aurora A kniase inhibitor MLN8237 in advanced solid tumors: safety, pharmacokinetics, pharmacodynamics, and bioavailability of two oral formulations. Clin Cancer Res 2012; 18:4775-4784.
- 1. Dammert MA, Brägelmann J, et al. "MYC paralog-dependent apoptotic priming orchestrates a spectrum of vulnerabilities in small cell lung cancer." Nat Commun. 2019 Aug 2;10(1):3485. PMID:31375684
- 2. Laura Tomino, Emily Bopp, et al. "Combinatorial BRD4 and AURKA inhibition is synergistic against preclinical models of Ewing sarcoma." Cancer reports. 11 February 2019.
- 3. Shaon Parial. "Novel Interaction, Regulation of Phosphorylation and Mitotic Localization of Cell Division Cycle Associated Protein 7 (CDCA7)" York University.2018.
- 4. Teke K, Yilmaz H, et al. "Histopathologic and molecular comparative analyses of intravesical Aurora kinase-A inhibitor Alisertib with bacillus Calmette-Guérin on precancerous lesions of bladder in a rat model." Int Urol Nephrol. 2018 Jun 21. PMID:29931492
- 5. Krulikas LJ, McDonald IM, et al. "Application of Integrated Drug Screening/Kinome Analysis to Identify Inhibitors of Gemcitabine-Resistant Pancreatic Cancer Cell Growth." SLAS Discov. 2018 May 1:2472555218773045. PMID:29742358
- 6. Joshua Felgenhauer, Laura Tomino, et al. "Dual BRD4 and AURKA Inhibition is Synergistic against MYCN-amplified and nonamplified Neuroblastoma." bioRxiv.2018 Mar.5.
- 7. Mathison A, Salmonson A, et al."Combined AURKA and H3K9 Methyltransferase Targeting Inhibits Cell Growth By Inducing Mitotic Catastrophe." Mol Cancer Res. 2017 Aug;15(8):984-997. PMID:28442587
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 518.92 |
| Cas No. | 1028486-01-2 |
| Formula | C27H20ClFN4O4 |
| Solubility | ≥25.95 mg/mL in DMSO; insoluble in H2O; insoluble in ETOH |
| Chemical Name | 4-[[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]-2-methoxybenzoic acid |
| SDF | Download SDF |
| Canonical SMILES | COC1=C(C(=CC=C1)F)C2=NCC3=CN=C(N=C3C4=C2C=C(C=C4)Cl)NC5=CC(=C(C=C5)C(=O)O)OC |
| 运输条件 | 蓝冰运输或根据您的需求运输。 |
| 一般建议 | 不同厂家不同批次产品溶解度各有差异，仅做参考。若实验所需浓度过大至产品溶解极限，请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存，请尽快用完。 |
| 细胞实验[1]： | |
|
细胞系 |
TIB-48和CRL-2396细胞 |
|
溶解方法 |
在DMSO中的溶解度 >10 mM。为了获得更高的浓度，可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。 |
|
反应条件 |
>100 nM；48 h |
|
应用 |
TIB-48和CRL-2396细胞分别用10 nM、50 nM、100 nM、500 nM和1.0 μM的MLN8237处理48小时，在>100 nM浓度时，MLN8237诱导细胞凋亡，表明其是剂量依赖的。在处理的TIB-48和CRL-2396细胞中，切割PARP的水平增加，即使在MLN8237浓度低至50 nM时也能观察到PARP切割。 |
| 动物实验[2]： | |
|
动物模型 |
植入OVCAR-5-pWZL-Luc细胞的雌性C.B-17 SCID小鼠 |
|
剂量 |
20或30 mg/kg，1次/天（QD）或2次/天（BID）；口服给药 |
|
应用 |
小鼠（n=16/组）随机分成5组：1）对照；2）20 mg/kg alisertib；3）30 mg/kg alisertib；4）5 mg/kg paclitaxel；5）20 mg/kg alisertib + 5 mg/kg paclitaxel。用每周BLI监测肿瘤生长。对数转换总通量数据表明，与对照小鼠相比，alisertib （20或30 mg/kg）治疗小鼠显著减少肿瘤生长速度，分别导致51％和49％的TGI。 |
|
注意事项 |
请测试所有化合物在室内的溶解度，实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的，属于正常现象。 |
|
References: [1] Qi W, Spier C, Liu X, et al. Alisertib (MLN8237) an investigational agent suppresses Aurora A and B activity, inhibits proliferation, promotes endo-reduplication and induces apoptosis in T-NHL cell lines supporting its importance in PTCL treatment. Leukemia research, 2013, 37(4): 434-439. [2] Do T V, Xiao F, Bickel L E, et al. Aurora kinase A mediates epithelial ovarian cancer cell migration and adhesion. Oncogene, 2013, 33(5): 539-549. |
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| 描述 | Alisertib (MLN8237)是一种选择性的Aurora A抑制剂，IC50值为1.2 nM，对Aurora A的选择性比对Aurora B高200倍以上。 | |||||
| 靶点 | Aurora A | |||||
| IC50 | 1.2 nM | |||||
质量控制和MSDS
- 批次:
化学结构
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