133407-82-6 MG-132 细胞通透性的、可逆性的蛋白酶体YZ剂。

 MG-132 细胞通透性的、可逆性的蛋白酶体YZ剂。 货号：A2585  规格：10mg/500元  现货  原装进口

化学性质

CAS号	133407-82-6
别名	MG132,Z-LLL-al,Z-Leu-Leu-Leu-CHO
化学名	benzyl N-[(2S)-4-methyl-1-[[(2S)-4-methyl-1-[[(2S)-4-methyl-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]carbamate
SMILES	CC(C)CC(C=O)NC(=O)C(CC(C)C)NC(=O)C(CC(C)C)NC(=O)OCC1=CC=CC=C1
分子式	C26H41N3O5	分子量	475.6
溶解性	>23.8mg/mL in DMSO	储存条件	Store at 4°C
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。储液可以在零下20℃中保存数月。
运输条件	SY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。

生物活性MG-132 细胞通透性的、可逆性的蛋白酶体YZ剂。

描述	MG-132是一种蛋白酶体YZ剂，IC50为100 nM，也可以YZ钙蛋白酶，IC50为1.2 μM。
靶点	Proteasome
IC50	100 nM

实验操作

激酶实验：
MG-132对蛋白酶体9的YZ活性	MG-132是一种肽醛，可以有效阻断蛋白酶体9的蛋白水解活性。已有研究表明，蛋白酶体的YZ剂 （包括MG-132）通过形成活性氧（ROS）从而诱导凋亡性细胞死亡。蛋白酶体YZ剂引起的ROS的形成和谷胱甘肽（GSH）的耗竭可能导致线粒体功能障碍和随后细胞色素c的释放，从而导致细胞活力的丧失[1，2]。
细胞实验：
细胞系	A549细胞、人宫颈癌HeLa细胞、HT-29结肠癌细胞、MG-63骨肉瘤细胞等。
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。
反应时间	24-48小时
应用	MG-132是一种膜通透性的蛋白酶体YZ剂。在PC12细胞中，MG-132（10 μM） 可用于诱导神经突触的生长。MG-132剂量依赖地YZA549细胞的生长，IC50值为20 μM。MG-132也可以YZ人宫颈癌Hela细胞的生长，IC50值约为5 μM。0.5 μM的MG-132就可以显著减少Hela细胞的生长，诱导细胞死亡[3]。MG-132通过诱导G2 / M期细胞周期停滞从而YZHT-29结肠癌细胞和MG-63骨肉瘤细胞的生长[5]。在氯化锰处理的A549细胞中，MG-132延长G0 / G1期停滞的时间。MG-132也可以诱导胃癌细胞中G1期停滞[6]。
动物实验：
动物模型	C57BL小鼠
剂量	~10 μg/kg/天，尾静脉或腹腔注射。
溶解方法	溶解于DMSO中用于制备10 mg/ml的储备原液，工作液可用PBS或生理盐水进行稀释，pH等于7。
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. Ling YH, Liebes L, Zou Y and Perez-Soler R. Reactive oxygen species generation and mitochondrial dysfunction in the apoptotic response to Bortezomib, a novel proteasome inhibitor, in human H460 non-small cell lung cancer cells, 2003; 278: 33714–33723. 2. Qiu JH, Asai A, Chi S, et al. Proteasome inhibitors induce cytochrome c-caspase-3-like protease-mediated apoptosis in cultured cortical neurons. J Neurosci 2000; 20: 259–265. 3. YH. Han, WH. Park, MG132 as a proteasome inhibitor induces cell growth inhibition and cell death in A549 lung cancer cells via influencing reactive oxygen species and GSH level, Human and Experimental Toxicology, 29(7) 607–614. 4. Wu WK, Wu YC, Yu L, et al. Induction of autophagy by proteasome inhibitor is associated with proliferative arrest in colon cancer cells. Biochem Biophys Res Commun 2008; 374: 258–263. 5. Yan XB, Yang DS, Gao X, et al. Caspase-8 dependent osteosarcoma cell apoptosis induced by proteasome inhibitor MG132. Cell Biol Int 2007; 31: 1136–1143. 6. ZhangW, Tong Q, Li S, Wang X andWang Q.MG-132 inhibits omerase activity, induces apoptosis and G(1) arrest associated with upregulated p27kip1 expression and downregulated survivin expression in gastric carcinoma cells. Cancer Invest 2008; 26:1032–1036.

View Related Products By Research Topics

• Neuroscience
• Cancer Biology
• Ubiquitination
• NF-kB

研究更新

1. Proteasome inhibitor MG-132 induces MCPIP1 expression. FEBS J. 2013 Jun;280(11):2665-74. doi: 10.1111/febs.12264. Epub 2013 May 7. 
Abstract 
MG-132 significantly increased MCPIP1 expression through a mechanism involving de novo mRNA synthesis and activated apoptosis through induction of caspases 3/7 in HepG2 and HeLa cells.

2. Therapeutic effect of MG-132 on diabetic cardiomyopathy is associated with its suppression of proteasomal activities: roles of Nrf2 and NF-κB. Am J Physiol Heart Circ Physiol. 2013 Feb 15;304(4):H567-78. doi: 10.1152/ajpheart.00650.2012. Epub 2012 Dec 7. 
Abstract 
Intraperitoneal administration of MG-132 reversed several pathogenic changes in OVE26 diabetic mice though up-regulation of Nrf2-mediated antioxidative function and down-regulation of NF-KB-mediated inflammation.

3. Noxa/Mcl-1 balance influences the effect of the proteasome inhibitor MG-132 in combination with anticancer agents in pancreatic cancer cell lines. Anticancer Drugs. 2012 Jul;23(6):614-26. doi: 10.1097/CAD.0b013e3283504e53. 
Abstract 
The combination of MG-132 and camptothecin exhibited strongest cytotoxicity against MIA PaCa-2 pancreatic cancer cells though promoting apoptosis induced by caspase-3 that is possibly associated with up-regulation of Noxa and down-regulation of Mcl-1. However, the combination of MG-132 and doxorubicin exhibited less cytotoxicity due to decreased apoptosis correlated with high levels of Mcl-1.

4. DJ-1 protein protects dopaminergic neurons against 6-OHDA/MG-132-induced neurotoxicity in rats. Brain Res Bull. 2012 Sep 1;88(6):609-16. doi: 10.1016/j.brainresbull.2012.05.013. Epub 2012 Jun 1. 
Abstract 
Administration of DJ-1 protein in rats pre-treated with MG-132 resulted in the reduction of α-synuclein mRNA, hypoxia-inducible factor 1α mRNA and α-synuclein protein.

5. The role of Src protein in the process formation of PC12 cells induced by the proteasome inhibitor MG-132. Neurochem Int. 2013 Nov;63(5):413-22. doi: 10.1016/j.neuint.2013.07.008. Epub 2013 Jul 31. 
Abstract 
MG-132, a peptidyl-aldehyde proteasome inhibitor, induced differentiation of PC12 cells that was accompanied by phosphorylation of TrkA, prolonged activation of Src and activation of ERK1/2 with nuclear translocation of Src.

产品描述

MG132是一种肽醛，可以有效地阻断蛋白酶体的蛋白水解活性， 包含苄酯基 - 亮氨酸 - 亮氨酸 - 亮氨酸序列。据报道，蛋白酶体的YZ剂 （包括MG132）可以通过形成活性氧（ROS）从而诱导细胞凋亡。蛋白酶体YZ剂引起的ROS的形成和谷胱甘肽（GSH）的耗竭可导致线粒体功能障碍和随后细胞色素c的释放，从而导致细胞活力的丧失。

MG132剂量依赖性地YZA549细胞的生长，IC50值为20 μM。MG-132也可以YZ人宫颈癌Hela细胞的生长，IC50值为5 μM。同样的，0.5 μM的MG-132就可以显著减少Hela细胞的生长，并诱导细胞死亡。MG132对细胞生长的YZ取决于孵育的剂量和细胞类型。

MG132可以显著阻滞G1期。MG-132通过诱导G2 / M期阻滞从而YZHT-29结肠癌细胞和MG-63骨肉瘤细胞的生长。在氯化锰处理的A549细胞中，MG-132可以延长G0 / G1期阻滞。同时，MG-132可以诱导胃癌细胞中G1期的阻滞。MG132对泛素-蛋白酶体系统的作用可能导致不同的细胞周期阻滞，这取决于不同的肿瘤细胞系。

已有研究表明，蛋白酶体的YZ剂 （包括MG132）可以通过形成活性氧（ROS）从而诱导凋亡性细胞死亡。MG132通过诱导细胞周期阻滞从而触发细胞凋亡，从而YZA549细胞的生长，这与ROS和GSH水平的变化具有一定的相关性。

参考文献：
1.  Ling YH, Liebes L, Zou Y and Perez-Soler R. Reactive oxygen species generation and mitochondrial dysfunction in the apoptotic response to Bortezomib, a novel proteasome inhibitor, in human H460 non-small cell lung cancer cells, 2003; 278: 33714–33723.
2.  Qiu JH, Asai A, Chi S, et al. Proteasome inhibitors induce cytochrome c-caspase-3-like protease-mediated apoptosis in cultured cortical neurons. J Neurosci 2000; 20: 259–265.
3.  YH. Han, WH. Park, MG132 as a proteasome inhibitor induces cell growth inhibition and cell death in A549 lung cancer cells via influencing reactive oxygen species and GSH level, Human and Experimental Toxicology, 29(7) 607–614.
4.  Wu WK, Wu YC, Yu L, et al. Induction of autophagy by proteasome inhibitor is associated with proliferative arrest in colon cancer cells. Biochem Biophys Res Commun 2008; 374: 258–263.
5.  Yan XB, Yang DS, Gao X, et al. Caspase-8 dependent osteosarcoma cell apoptosis induced by proteasome inhibitor MG132. Cell Biol Int 2007; 31: 1136–1143.
6.  ZhangW, Tong Q, Li S, Wang X andWang Q.MG-132 inhibits omerase activity, induces apoptosis and G(1) arrest associated with upregulated p27kip1 expression and downregulated survivin expression in gastric carcinoma cells. Cancer Invest 2008; 26:1032–1036.
7.  Wu HM, Chi KH, Lin WW. Proteasome inhibitors stimulate activator protein-1 pathway via reactive oxygen species production. FEBS Lett 2002; 526: 101–105.