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MLN9708

现货
Catalog No.
A4007
蛋白酶体抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,050.00
现货
5mg
¥ 900.00
现货
10mg
¥ 1,500.00
现货
50mg
¥ 4,500.00
现货
100mg
¥ 6,400.00
现货

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Background

MLN9708, also known as ixazomib, is a second-generation small-molecule proteasome inhibitor. It is a citrate ester that immediately hydrolyzes to its biologically active form MLN2238 upon exposure to aqueous solutions or plasma. MLN9708 was selected from a large pool of boron-containing proteasome inhibitors based on a physicochemical profile that was distinct from bortezomib. MLN9708 has a shorter 20S proteasome dissociation half-life than bortezomib, which is demonstrated to play an important role in its improved tissue distribution.

Reference

Erik Kupperman, Edmund C. Lee, Yueying Cao, Bret Bannerman, Michael Fitzgerald, Allison Berger, Jie Yu, Yu Yang, Paul Hales, Frank Bruzzese, Jane Liu, Jonathan Blank, Khristofer Garcia, Christopher Tsu, Larry Dick, Paul Fleming, Li Yu, Mark Manfredi, Mark Rolfe, and Joe Bolen. Evaluation of the Proteasome Inhibitor MLN9708 in Preclinical Models of Human Cancer. Cancer Res March 1, 2010 70; 1970.

Edmund C. Lee, Michael Fitzgerald, Bret Bannerman, Jill Donelan, Kristen Bano, Jennifer Terkelsen, Daniel P. Bradley, Ozlem Subakan, Matthew D. Silva, Ray Liu, Michael Pickard, Zhi Li, Olga Tayber, Ping Li, Paul Hales, Mary Carsillo, Vishala T. Neppalli, Allison J. Berger, Erik Kupperman, Mark Manfredi, Joseph B. Bolen, Brian Van Ness, Siegfried Janz. Antitumor Activity of the Investigational Proteasome Inhibitor MLN9708 in Mouse Models of B-cell and Plasma Cell Malignancies. Clin Cancer Res December 1, 2011 17; 7313.

文献引用

1. Mañas A, Chen W, et al. "BaxΔ2 sensitizes colorectal cancer cells to proteasome inhibitor-induced cell death." Biochem Biophys Res Commun. 2018 Jan 29;496(1):18-24. PMID:29291406
2. Li H, Chen Z, et al. "Novel proteasome inhibitor ixazomib sensitizes neuroblastoma cells to doxorubicin treatment." Sci Rep. 2016 Sep 30;6:34397. PMID:27687684
3. Wang H, Yu Y, et al. "Next-generation proteasome inhibitor MLN9708 sensitizes breast cancer cells to doxorubicin-induced apoptosis." Sci Rep. 2016 May 24;6:26456. PMID:27217076

Chemical Properties

StorageStore at -20°C
M.Wt517.1
Cas No.1201902-80-8
FormulaC20H23BCl2N2O9
SynonymsMLN-9708, MLN 9708
Solubility≥20.85 mg/mL in DMSO, ≥4.56 mg/mL in EtOH with ultrasonic and warming, <2.32 mg/mL in H2O
Chemical Name[(1R)-1-[[2-[(2,5-dichlorobenzoyl)amino]acetyl]amino]-3-methylbutyl]boronic acid
SDFDownload SDF
Canonical SMILESB1(OC(=O)CC(O1)(CC(=O)O)C(=O)O)C(CC(C)C)NC(=O)CNC(=O)C2=C(C=CC(=C2)Cl)Cl
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。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。

试验操作

细胞实验[1]:

细胞系

MM.1S(地塞米松敏感)细胞

溶解方法

该化合物在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应条件

CT-L蛋白酶体抑制:100 nM,3小时;C-L蛋白酶体抑制:100 nM,3小时;T-L蛋白酶体抑制:10 μM,3小时。

实验结果

MLN9708显著抑制CT-L蛋白酶体活性,IC50为5 nM。较高浓度的MLN9708抑制C-L和T-L蛋白酶体的活性。

动物实验[2]:

动物模型

携带WSU-DLCL2异种移植物的雌性CB17-SCID小鼠

剂量

静脉注射,14 mg/kg,每周两次或皮下注射,4 mg/kg,每日一次

实验结果

间歇和连续的MLN2238给药方案显示出强的抗肿瘤活性,14 mg/kg 静脉内注射以及4 mg/kg皮下注射的T/C分别为0.44和0.29,通过测量切割的caspase-3水平发现,肿瘤组织中产生较强的凋亡反应。

注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[1] Chauhan D, Tian Z, Zhou B, et al. In vitro and in vivo selective antitumor activity of a novel orally bioavailable proteasome inhibitor MLN9708 against multiple myeloma cells. Clinical Cancer Research, 2011, 17(16): 5311-5321.

[2] Kupperman E, Lee E C, Cao Y, et al. Evaluation of the proteasome inhibitor MLN9708 in preclinical models of human cancer. Cancer research, 2010, 70(5): 1970-1980.

质量控制

化学结构

MLN9708

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MLN9708

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