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MG-132Proteasome inhibitor, Cell permeable, reversible

MG-132

Catalog No. A2585
Size Price Stock Qty
10mM (in 1mL DMSO) $65.00 In stock
Evaluation Sample $28.00 In stock
10mg $50.00 In stock
25mg $120.00 In stock
100mg $320.00 In stock
500mg $980.00 In stock

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Sample solution is provided at 25 µL, 10mM.

Product Citations

1. Giovinazzi S, Sirleto P, Aksenova V, et al. Usp7 protects genomic stability by regulating Bub3[J]. Oncotarget, 2014, 5(11): 3728. PubMed: PMC4116516
2. Boyd-Tressler, Andrea, et al. "Chemotherapeutic Drugs Induce ATP Release via Caspase-gated Pannexin-1 Channels and a Caspase/Pannexin-1-Independent Mechanism." Journal of Biological Chemistry (2014): jbc-M114. PMID:25112874
3. Baeten, Jeremy T., and Brenda Lilly. "Differential Regulation of NOTCH2 and NOTCH3 Contribute to their Unique Functions in Vascular Smooth Muscle Cells." Journal of Biological Chemistry (2015): jbc-M115. PMID:25957400
4. Moshe, Adi, et al. "Tomato plant cell death induced by inhibition of HSP90 is alleviated by Tomato yellow leaf curl virus infection." Molecular plant pathology (2015). PMID:25962748
5. Gunderwala A, Porter J. "A luminescence assay for natural product inhibitors of the Mycobacterium tuberculosis proteasome." Phytochem Anal. 2016 Mar;27(2):126-32. PMID:26778282

Quality Control

Related Biological Data

MG-132
MG132 alone induced cleavage of the Panx1 autoinhibitory domain which was co-temporal with proteolytic processing PARP1 [1].
1. Boyd-Tressler A, Penuela S, Laird D W, et al. Chemotherapeutic Drugs Induce ATP Release via Caspase-gated Pannexin-1 Channels and a Caspase/Pannexin-1-Independent Mechanism. Journal of Biological Chemistry, 2014: jbc. M114. 590240.

Related Biological Data

MG-132
HeLa cells were untreated (-) or treated with 10 μm MG-132 (+) as indicated, 4 h later the cells were harvested and the lysates were subjected to immunoblot analysis with anti-ubiquitin or anti-p53 antibodies.

Related Biological Data

MG-132
U2O2 cells were treated with MG-132 or PSI for 0, 1, 2, and 3 hours.

Related Biological Data

MG-132
The p53 level in H446 cells is low, and MG132 inhibits the p53 degradation effectively.
Method:Immunoblot assays; Cell Lines:H446 cells; Concentrations:5-20 μM; Incubation Time:12 h.

Related Biological Data

MG-132

Related Biological Data

MG-132

Biological Activity

Description MG-132 is an inhibitor of proteasome with IC50 of 100 nM, and also inhibits calpain with IC50 of 1.2 μM.
Targets Proteasome          
IC50 100 nM          

Protocol

Kinase experiment:

Inhibitory activities of MG-132 towards proteasome complex 9

MG-132 acts as a peptide aldehyde effectively blocks the proteolytic activity of proteasome complex 9. Proteasome inhibitors including MG-132 have been shown to induce apoptotic cell death through formation of ROS. ROS formation and GSH depletion due to proteasome inhibitors may cause mitochondrial dysfunction and subsequent cytochrome C release, which leads to cell viability loss [ 1, 2].

Cell experiment:

Cell lines

A549 cells, human cervical HeLa cancer cells, HT-29 colon cancer cells, MG-63 osteosarcoma cell etc.

Preparation method

The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.

Acting time

24-48 h

Applications

MG-132 is a membrane-permeable proteasome inhibitor. It is used to Induce neurite outgrowth in PC12 cells at 10 μM. MG132 dose dependently inhibited the growth of A549 cells with an IC50 of approximately 20 µM. MG-132 also reduced the growth of human cervical HeLa cancer cells with an IC50 of approximately 5 µM. Treatment with 0.5 µM MG-132 significantly decreased the growth of HeLa cells and induced cell death as well [3]. MG-132 inhibits the growth of HT-29 colon cancer cells via inducing G2/M cell cycle arrest [4], causes MG-63 osteosarcoma cell arrest at G2/M phase [5], prolongs the duration of G0/G1 arrest in MnCl2-treated A549 cells and induces a G1 arrest in gastric carcinoma cells [6]. 

Animal experiment [3]:

Animal models

C57BL mice

Dosage form

~10 ug/kg/day, injection from tail vein or belly

Preparation method

Powder dissolved in DMSO to prepare stock solution with 10 mg/ml, and working solution is diluted by PBS or Saline. pH equals to 7.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

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 telomerase 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.

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Chemical Properties

Cas No. 133407-82-6 SDF Download SDF
Synonyms MG132,Z-LLL-al,Z-Leu-Leu-Leu-CHO
Chemical Name 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
Canonical SMILES CC(C)CC(C=O)NC(=O)C(CC(C)C)NC(=O)C(CC(C)C)NC(=O)OCC1=CC=CC=C1
Formula C26H41N3O5 M.Wt 475.6
Solubility Soluble in DMSO > 10 mM Storage Store at -20°C
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
Shipping Condition Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request

View Related Products By Research Topics

Research Update

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.

Background

MG132 (carbobenzoxy-Leu-Leu-leucinal) as a peptide aldehyde effectively blocks the proteolytic activity of proteasome complex.9 Proteasome inhibitors including MG132 have been shown to induce apoptotic cell death through formation of ROS. ROS formation and GSH depletion due to proteasome inhibitors may cause mitochondrial dysfunction and subsequent cytochrome c release, which leads to cell viability loss1, 2.

MG132 dose dependently inhibited the growth of A549 cells with an IC50 of approximately 20 µM. MG132 also reduced the growth of human cervical HeLa cancer cells with an IC50 of approximately 5 µM. Treatment with 0.5 µM MG132 significantly decreased the growth of HeLa cells and induced cell death as well. Cell growth inhibition by MG132 depends on incubation doses of that and cell types3.

MG132 significantly induced a G1 phase arrest of the cell cycle. It inhibits the growth of HT-29 colon cancer cells via inducing G2/M cell cycle arrest4, causes MG-63 osteosarcoma cell arrest at G2/M phase5, prolongs the duration of G0/G1 arrest in MnCl2-treated A549 cells21 and induces a G1 arrest in gastric carcinoma cells6. Deregulation of the ubiquitin-proteasomal system by MG132 can result in different cell cycle phase arrests depending on various cancer cell lines.

Proteasome inhibitors including MG132 have been shown to induce apoptotic cell death through formation of ROS1, 2, 7.  MG132 inhibited the growth of human A549 cells via inducing the cell cycle arrest as well as triggering apoptosis, which was in part correlated with the changes of ROS and GSH levels.

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 telomerase 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.