• 欢迎来到美国APExBIO中文站,专注小分子抑制剂、激动剂、拮抗剂及化合物库!

 


加 微 信 得 红 包
ApexBio
Search Site
相关产品
MLN9708蛋白酶体抑制剂

MLN9708

产品编号:A4007
ApexBio 的所有产品仅用作科研,我们不为任何个人用途提供产品和服务
规格 单价 库存 订购数量
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

电话: 021-55669583

Email: sales@apexbio.cn

全球经销商

Sample solution is provided at 25 µL, 10mM.

引用文献

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

质量控制

化学结构

MLN9708

相关生物数据

MLN9708

相关生物数据

MLN9708

相关生物数据

MLN9708

相关生物数据

MLN9708

相关生物数据

MLN9708

MLN9708 Dilution Calculator

Concentration (start)
x
Volume (start)
=
Concentration (final)
x
Volume (final)
 
 
 
C1
V1
C2
V2

calculate

MLN9708 Molarity Calculator

Mass
=
Concentration
x
Volume
x
MW*
 
 
 
g/mol

calculate

化学性质

CAS号 1201902-80-8 SDF Download SDF
别名 MLN-9708, MLN 9708
化学名 [(1R)-1-[[2-[(2,5-dichlorobenzoyl)amino]acetyl]amino]-3-methylbutyl]boronic acid
SMILES B1(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
分子式 C20H23BCl2N2O9 分子量 517.1
溶解度 ≥20.85 mg/mL in DMSO, ≥4.56 mg/mL in EtOH with ultrasonic and warming, <2.32 mg/mL in H2O 储存条件 Store at -20°C
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。

实验操作

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.

研究更新

1. Syntheses of C-13 and C-14-labeled versions of the investigational proteasome inhibitor MLN9708. J Labelled Comp Radiopharm. 2013 Jul-Aug;56(9-10):464-70. doi: 10.1002/jlcr.3079. Epub 2013 Jul 9.
Abstract
Radiolabeled MLN9708, a proteasome inhibitor with antitumor activity, were synthesized and evaluated for its stability.
2. Antitumor activity of the investigational proteasome inhibitor MLN9708 in mouse models of B-cell and plasma cell malignancies. Clin Cancer Res. 2011 Dec 1;17(23):7313-23. doi: 10.1158/1078-0432.CCR-11-0636. Epub 2011 Sep 8.
Abstract
MLN9708 is a proteasome inhibitor with improved pharmacokinetics, pharmacodynamics and antitumor activity in comparison to bortezomib.
3. Investigational agent MLN9708/2238 targets tumor-suppressor miR33b in MM cells. Blood. 2012 Nov 8;120(19):3958-67. doi: 10.1182/blood-2012-01-401794. Epub 2012 Sep 14.
Abstract
MLN2238, a proteasome inhibitor, induced the expression of miR33b predominantly through transcriptional regulation and negatively regulated oncogene PIM-1 blocking wild-type PIM-1 in MM cells.
4. Preclinical Activity of the Oral Proteasome Inhibitor MLN9708 in Myeloma Bone Disease. Clin Cancer Res. 2014 Feb 27. [Epub ahead of print]
Abstract
MLN2238, an active form of MLN9708, inhibited in vitro osteoclastogenesis and osteoclast resorption and promoted in vitro osteoblastogensis and osteoblast activity at clinically achievable concentrations. Compared to bortezomib, oral administration of MLN2238 exhibited equivalent tumor burden controlling efficacy with a marked benefit in associated bone disease.

产品描述

MLN9708,也称为ixazomib,是一种第二代小分子蛋白酶体抑制剂。MLN9708是一种柠檬酸酯,接触水溶液或血浆后立即水解为其生物活性形式MLN2238。基于与bortezomib不同的物理化学特征,MLN9708选自大量含硼蛋白酶体抑制剂。MLN9708具有比bortezomib更短的20S 蛋白酶体分解半衰期,这对其改善的组织分布发挥重要作用。

参考文献:
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.