A2585-10mg | MG-132 [133407-82-6] Hexabiogen

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 loss^{1, 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 cells 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 ROS^{1, 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.

Product Citation

1. Yao Gong, Gaurav Behera, et al. "HypDB: A functionally annotated web-based database of the proline hydroxylation proteome." PLoS Biol. 2022 Aug 26;20(8):e3001757. PMID: 36026437
2. Yang Liu, Libo He, et al. "Pharmacological inhibition of sphingolipid synthesis reduces ferroptosis by stimulating the HIF-1 pathway." iScience. 2022 Jun 6;25(7):104533. PMID: 35784791
3. Ray W. Bowman II , Eric M. Jordahl, et al. "TORC1 Signaling Controls the Stability and Function of α-Arrestins Aly1 and Aly2." Biomolecules. 2022 Mar 31;12(4):533. PMID: 35454122
4. Li Song, Lin Zhang, et al. "ORP5 promotes tumor metastasis via stabilizing c-Met in renal cell carcinoma." Cell Death Discov. 2022 Apr 21;8(1):219. PMID: 35449154
5. Zhuoyao Chen, Rafael M Ioris, et al. "Disease-associated KBTBD4 mutations in medulloblastoma elicit neomorphic ubiquitylation activity to promote CoREST degradation." Cell Death Differ. 2022 Oct;29(10):1955-1969. PMID: 35379950
6. Rui Zhang, Teng Xue, et al. "Bclaf1 regulates c‐FLIP expression and protects cells from TNF‐induced apoptosis and tissue injury." EMBO Rep. 2021 Oct 25;e52702. PMID: 34693625
7. Yang Liu, Libo He, et al. "Stable maintenance of the Mre11-Rad50-Nbs1 complex is sufficient to restore the DNA double-strand break response in cells lacking RecQL4 helicase activity." J Biol Chem. 2021 Oct;297(4):101148. PMID: 34473993
8. Marina Dall’Osto, Laura Pierini, et al. "A Catalytically Independent Function of Human DNA Polymerase Kappa Controls the Stability and Abundance of Checkpoint Kinase 1." Mol Cell Biol. 2021 Oct 26;41(11):e0009021. PMID: 34398682
9. Du Yu, Yundi Zhao, et al. "C19orf66 Inhibits Japanese Encephalitis Virus Replication by Targeting -1 PRF and the NS3 Protein." Virol Sin. 2021 Dec;36(6):1443-1455. PMID: 34309824
10. Xiaowei Fei, Ya-nan Dou, et al. "TRIM22 Activates MAPK Signaling by Regulating the Transcription of SPHK2 and Accelerating the Degradation of Raf-1 in Glioblastoma." Research Square. November 10th, 2021.
11. Shaojun Wu, Ying Zhang, et al. "Septin4 promotes cardiomyocytes apoptosis by enhancing the VHL-mediated degradation of HIF-1α." Cell Death Discov. 2021 Jul 6;7(1):172. PMID: 34230460
12. Yaqi Cui, Rong Xie, et al. "OGA is associated with deglycosylation of NONO and the KU complex during DNA damage repair." Cell Death Dis. 2021 Jun 16;12(7):622. PMID: 34135314
13. Xu Z, Hu H, et al. "The deubiquitinase USP38 promotes cell proliferation through stabilizing c-Myc." Int J Biochem Cell Biol. 2021 Aug;137:106023. PMID: 34102342
14. Sonali Bahl, Hongbo Ling, et al. "EGFR phosphorylates HDAC1 to regulate its expression and anti-apoptotic function." Cell Death Dis. 2021 May 11;12(5):469. PMID: 33976119
15. Yeonghyeon Lee, Jaejin Kim, et al. "Coordinate regulation of the senescent state by selective autophagy." Dev Cell. 2021 May 17;56(10):1512-1525.e7. PMID: 33915088
16. Qiang Li, Dongmei Yu, et al. "TIPE3 promotes non-small cell lung cancer progression via the protein kinase B/extracellular signal-regulated kinase 1/2-glycogen synthase kinase 3β-β-catenin/Snail axis." Transl Lung Cancer Res. 2021 Feb;10(2):936-954. PMID: 33718034
17. Qiu Fang, Fanglin Zhou, et al. "Degradation of STOP1 mediated by the F-box proteins RAH1 and RAE1 balances aluminum resistance and plant growth in Arabidopsis thaliana." Plant J. 2021 Apr;106(2):493-506. PMID: 33528836
18. Weiwei Qin, Xiyang Tong, et al. "Preservation of mitochondrial homeostasis is responsible for the ameliorative effects of Suhuang antitussive capsule on non-resolving inflammation via inhibition of NF-κB signaling and NLRP3 inflammasome activation." J Ethnopharmacol. 2021 May 10;271:113827. PMID: 33460751
19. Hyeonkyeong Kim, Yongsik Cho, et al. "A system-level approach identifies HIF-2α as a critical regulator of chondrosarcoma progression." Nat Commun. 2020 Oct 6;11(1):5023. PMID: 33024108
20. Hyun-Soo Kim, Benjamin Roche, et al. "Clr4SUV39H1 and Bdf2BRD4 ubiquitination mediate transcriptional silencing via heterochromatic phase transitions." bioRxiv. January 8, 2021.
21. Yanmin Zhong, Xin Li, et al. "The S-nitrosylation of parkin attenuated the ubiquitination of divalent metal transporter 1 in MPP+-treated SH-SY5Y cells." Sci Rep. 2020 Sep 23;10(1):15542. PMID: 32968192
22. Rilin Deng, Chaohui Zuo, et al. "The innate immune effector ISG12a promotes cancer immunity by suppressing the canonical Wnt/β-catenin signaling pathway." Cell Mol Immunol. 2020 Nov;17(11):1163-1179. PMID: 32963356
23. Shaojun Wu, Ying Zhang, et al. "Septin4 Aggravates Hypoxia-Induced Cardiomyocytes Injury by Promoting HIF-1α Ubiquitination and Degradation through VHL." Research Square. October 21st, 2020.
24. Dong Yuan, Yiyu Chen, et al. "SPOP attenuates migration and invasion of choriocarcinoma cells by promoting DHX9 degradation." Am J Cancer Res. 2020; 10(8): 2428–2445. PMID: 32905556
25. Jianxiong Ji, Kaikai Ding, et al. "TRIM22 activates NF-κB signaling in glioblastoma by accelerating the degradation of IκBα." Cell Death Differ. 2021 Jan;28(1):367-381. PMID: 32814880
26. Dana Mamriev, Ruqaia Abbas, et al. "A small-molecule ARTS mimetic promotes apoptosis through degradation of both XIAP and Bcl-2." Cell Death Dis. 2020 Jun 25;11(6):483. PMID: 32587235
27. Jinliang Guo, Yang Zhang, et al. "Mutation of HPR1 encoding a component of the THO/TREX complex reduces STOP1 accumulation and aluminium resistance in Arabidopsis thaliana." New Phytol. 2020 Oct;228(1):179-193. PMID: 32406528
28. Wang F, Wang H, et al. "TRIM59 Inhibits PPM1A through Ubiquitination and Activates TGF-β/Smad Signaling to Promote the Invasion of Ectopic Endometrial Stromal cells in Endometriosis." Am J Physiol Cell Physiol. 2020;10.1152/ajpcell.00127.2019. PMID: 32348176
29. Lang Y, Yu C, et al. "Characterization of porcine p53 and its regulation by porcine Mdm2." Gene. 2020;748:144699. PMID: 32334023
30. Dai J, Yang L, et al. "A Functional Synonymous Variant in PDGFRA Is Associated with Better Survival in Acral Melanoma." J Cancer. 2020;11(10):2945-2956. Published 2020 Mar 4. PMID: 32226509
31. Qian H, Zhang N, et al. "The E3 ubiquitin ligase Smurf2 regulates PARP1 stability to alleviate oxidative stress-induced injury in human umbilical vein endothelial cells." J Cell Mol Med. 2020;24(8):4600-4611. PMID: 32167680
32. Park JS, Burckhardt CJ, et al. "Mechanical regulation of glycolysis via cytoskeleton architecture." Nature. 2020;578(7796):621–626. PMID: 32051585
33. Xuyang Zhao, Yadong Ma, et al. "mTORC2 mediate FLCN-induced HIF2α nuclear import and proliferation of clear cell renal cell carcinoma." bioRxiv. 2020 January 13.
34. Greene KS, Lukey MJ, et al. "SIRT5 stabilizes mitochondrial glutaminase and supports breast cancer tumorigenesis." Natl Acad Sci U S A. 2019 Dec 16. pii: 201911954. PMID: 31843902
35. Zhou H, Du R, et al. "Cannabinoid receptor 2 promotes the intracellular degradation of HMGB1 via the autophagy-lysosome pathway in macrophage." Int Immunopharmacol. 2020;78:106007. PMID: 31806570
36. Matzinger M, Fischhuber K, et al. "AMPK leads to phosphorylation of the transcription factor Nrf2, tuning transactivation of selected target genes." Redox Biol. 2019 Nov 27;29:101393. PMID: 31805502
37. Chen Y, Zhu E, et al. "Important roles of C-terminal residues in degradation of capsid protein of classical swine fever virus." Virol J. 2019 Nov 6;16(1):127. PMID: 31694654
38. Sun J, Piao J, et al. "Valproic acid targets HDAC1/2 and HDAC1/PTEN/Akt signalling to inhibit cell proliferation via the induction of autophagy in gastric cancer." FEBS J. 2019 Nov 6.nbsp;PMID: 31692265
39. Kim S, Han S, et al. "Tankyrase inhibition preserves osteoarthritic cartilage by coordinating cartilage matrix anabolism via effects on SOX9 PARylation." Nat Commun. 2019 Oct 25;10(1):4898.nbsp;PMID: 31653858
40. Liu H, Ge XY, et al. "Up-regulation of cullin7 promotes proliferation and migration of pulmonary artery smooth muscle cells in hypoxia-induced pulmonary hypertension." Eur J Pharmacol. 2019 Sep 26;864:172698.nbsp;PMID: 31563647
41. Zhao T, Bao Y, et al. "DNA methylation-regulated QPCT promotes sunitinib resistance by increasing HRAS stability in renal cell carcinoma." Theranostics. 2019 Aug 14;9(21):6175-6190.nbsp;PMID: 31534544
42. Groborz K, Gonzalez Ramirez ML, et al. "Exploring the prime site in caspases as a novel chemical strategy for understanding the mechanisms of cell death: a proof of concept study on necroptosis in cancer cells." Cell Death Differ. 2020;27(2):451–465. PMID: 31209360
43. Casey Paulasue Nielsen. "Regulation of WNT pathway specification by DUB-E3 interactions." Vanderbilt University.2019
44. Yuan NN, Cai CZ, et al. "Canthin-6-One Accelerates Alpha-Synuclein Degradation by Enhancing UPS Activity: Drug Target Identification by CRISPR-Cas9 Whole Genome-Wide Screening Technology." Front Pharmacol. 2019 Jan 28;10:16.nbsp;PMID: 30745870
45. Ju L, Han J, et al. "Obesity-associated inflammation triggers an autophagy-lysosomal response in adipocytes and causes degradation of perilipin 1."Cell Death Dis. 2019 Feb 11;10(2):121. PMID: 30741926
46. Cui-ZanCai, He-FengZhou, et al. "Natural alkaloid harmine promotes degradation of Alpha-synuclein via PKA-mediated ubiquitin-proteasome system activation." Phytomedicine. Available online 30 January 2019, 152842.
47. Lee CH, Yang JR, et al. "Novel STAT3 Inhibitor LDOC1 Targets Phospho-JAK2 for Degradation by Interacting with LNX1 and Regulates the Aggressiveness of Lung Cancer." Cancers (Basel). 2019 Jan 9;11(1). pii: E63. PMID: 30634502
48. Dongdong Zhao, Jian Meng, et al. "RPS23RG1 is Required for Synaptic Integrity and Rescues Alzheimer’s Associated Cognitive Deficits." Biological Psychiatry Available online 25 August 2018.
49. Xiao G, Li Y, et al. "FBXW7 suppresses epithelial-mesenchymal transition and chemo-resistance of non-small-cell lung cancer cells by targeting snai1 for ubiquitin-dependent degradation." Cell Prolif. 2018 Aug 9:e12473. PMID: 30094882
50. Chao Qin, Rui Zhang, et al. "Bclaf1 critically regulates the type I interferon response and is degraded by alphaherpesvirus US3" bioRxiv. 2018 August 16.
51. Bao Y, Yang F, et al. "Angiopoietin-like protein 3 blocks nuclear import of FAK and contributes to sorafenib response." Br J Cancer. 2018 Jul 23. PMID: 30033448
52. Selvarangan Ponnazhagan, Vinayak Khattar, et al. "Structural determinants and genetic modifications enhance BMP2 stability and extracellular secretion." bioRxiv. 2018 July 20.
53. Ji J, Xu R, et al. "Actin like-6A promotes glioma progression through stabilization of transcriptional regulators YAP/TAZ."Cell Death Dis. 2018 May 3;9(5):517. PMID: 29725063
54. Lv XM, Li MD, et al."Neotuberostemonine inhibits the differentiation of lung fibroblasts into myofibroblasts in mice by regulating HIF-1α signaling." Acta Pharmacol Sin. 2018 Apr 12. PMID: 29645000
55. Lee S, Tumolo JM, et al. "Ubiquitin turnover and endocytic trafficking in yeast are regulated by Ser57 phosphorylation of ubiquitin." Elife. 2017 Nov 13;6. pii:e29176. PMID: 29130884
56. Wang Y, Lu S, et al. "Sonic hedgehog induces GLT-1 degradation via PKC delta to suppress its transporter activities." Neuroscience. 2017 Oct 6;365:217-225. PMID: 28993237
57. Wang Z, Gao Y, et al. "Quinolinate Phosphoribosyltransferase is an Antiviral Host Factor Against Hepatitis C Virus Infection." Sci Rep. 2017 Jul 19;7(1):5876. PMID: 28724915
58. Wang X, Liu X, et al. "Sensitivity to antitubulin chemotherapeutics is potentiated by a photoactivable nanoliposome." Biomaterials. 2017 Jun 23;141:50-62. PMID: 28667899
59. Ho HC, MacGurn JA, et al. "Deubiquitinating enzymes Ubp2 and Ubp15 regulate endocytosis by limiting ubiquitination and degradation of ARTs." Mol Biol Cell.2017 May 1;28(9):1271-1283. PMID: 28298493
60.Shanzer M, Adler J, et al. "The nonreceptor tyrosine kinase c-Src attenuates SCF(β-TrCP) E3-ligase activity abrogating Taz proteasomal degradation. "Proc Natl Acad Sci U S A. 2017 Feb 14;114(7):1678-1683. PMID: 28154141
61. Scott N. Ashley. "Impact Of Host Factors On The Adaptive Immune Response To Aav Gene Therapy." University of Pennsylvania. 2017.
62. Dr. Brenda Lilly, Advisor Dr. Joy Lincoln, et al. "The Roles of the Notch2 and Notch3 Receptors in Vascular Smooth Muscle Cells" The Ohio State University. 2016 Nov.
63. Liu Z, Moran GP, et al. "Amplification of TLO Mediator Subunit Genes Facilitate Filamentous Growth in Candida Spp." PLoS Genet. 2016 Oct 14;12(10):e1006373. PMID: 27741243
64. Boyd Tressler, Andrea Michelle. "Mechanisms of Extracellular Nucleotide Accumulation During Regulated Cell Death in Tumor Cells."rave.ohiolink.edu,May 2016.
65. 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
66. 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
67. 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
68. 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
69. Giovinazzi S, Sirleto P, et al. "Usp7 protects genomic stability by regulating Bub3." Oncotarget. 2014 Jun 15;5(11):3728-42. PMID: 25003721

Hide ↑↑

Chemical Properties

Storage	Store at -20°C The product is not stable in solution, please dissolve it immediately before use.
M.Wt	475.6
Cas No.	133407-82-6
Formula	C₂₆H₄₁N₃O₅
Synonyms	MG132,Z-LLL-al,Z-Leu-Leu-Leu-CHO
Solubility	≥23.78 mg/mL in DMSO; insoluble in H2O; ≥49.5 mg/mL in EtOH
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
SDF	Download SDF
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
Shipping Condition	Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice.
General tips	We do not recommend long-term storage for the solution, please use it up soon.

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 >23.8mg/mL. 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.
Reaction Conditions	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.