MG132

Biological Activity

MG132 is a potent cell-permeable inhibitor of proteasome and calpain with IC50 of 100 nM and 1.2 μM respectively. MG132 inhibited the growth of HeLa cells via inducing the cell cycle arrest as well as triggering apoptosis. MG132 also inhibits NF-κB activation with an IC50 of 3 µM and prevents β-secretase cleavage. MG132 induces cell apoptosis through formation of reactive oxygen species or the upregulation and downregulation of these factors, which is ultimately dependent upon the activation of the caspase family of cysteine proteases.

In vitro, it induces neurite outgrowth in PC12 cells and has anticancer properties. Besides its apoptotic effect alone, MG132 also enhanced the antiglioma effect of the chemotherapeutics cisplatin, taxol and doxorubicin in C6 and U138MG cells, indicating an adjuvant/chemosensitizer potential.

Product Citations

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  Exp Ther Med. 2022 Sep 23;24(5):687.

  MG132 protects against lung injury following brain death in rats
  MG132 purchased from AbMole

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  J Cell Mol Med. 2022 May;26(9):2646-2657.

  Venetoclax enhances DNA damage induced by XPO1 inhibitors: A novel mechanism underlying the synergistic antileukaemic effect in acute myeloid leukaemia
  MG132 purchased from AbMole

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  Bioengineered. 2022 Apr;13(4):8000-8012.

  UBE2B promotes ovarian cancer growth via promoting RAD18 mediated ZMYM2 monoubiquitination and stabilization
  MG132 purchased from AbMole

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  Virol Sin. 2022 Aug 16;S1995-820X(22)00143-2.

  CK1α upregulates the IFNAR1 expression to prompt the anti-HBV effect of type I IFN in hepatoma carcinoma cells
  MG132 purchased from AbMole

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  Ecotoxicol Environ Saf. 2022 Jun 1;237:113564.

  Environmental BPDE induced human trophoblast cell apoptosis by up-regulating lnc-HZ01/p53 positive feedback loop
  MG132 purchased from AbMole

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  Cell Death Differ. 2022 Jul;29(7):1395-1408.

  SARS-CoV-2 membrane protein causes the mitochondrial apoptosis and pulmonary edema via targeting BOK
  MG132 purchased from AbMole

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  Cell Death Dis. 2021 Oct 16;12(11):955.

  Essential role of zyxin in platelet biogenesis and glycoprotein Ib-IX surface expression
  MG132 purchased from AbMole

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  Cell Death Dis. 2021 Aug 21;12(9):803.

  USP14 maintains HIF1-α stabilization via its deubiquitination activity in hepatocellular carcinoma
  MG132 purchased from AbMole

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  Int J Mol Sci. 2021 Aug 16;22(16):8779.

  Autophagy Mediates the Degradation of Plant ESCRT Component FREE1 in Response to Iron Deficiency
  MG132 purchased from AbMole

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  J Cancer. 2021 Oct 17;12(23):7041-7051.

  N6-methyladenosine regulates ATM expression and downstream signaling
  MG132 purchased from AbMole

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  Adv Sci (Weinh). 2021 Jan 6;8(4):2003205.

  Inhibition Lysosomal Degradation of Clusterin by Protein Kinase D3 Promotes Triple-Negative Breast Cancer Tumor Growth
  MG132 purchased from AbMole

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  PLoS Pathog. 2021 Feb;17(2):e100899.

  CVB3 VP1 interacts with MAT1 to inhibit cell proliferation by interfering with Cdk-activating kinase complex activity in CVB3-induced acute
  MG132 purchased from AbMole

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  Cell Biol Toxicol. 2022 Apr;38(2):291-310.

  Lnc-HZ08 regulates BPDE-induced trophoblast cell dysfunctions by promoting PI3K ubiquitin degradation and is associated with miscarriage
  MG132 purchased from AbMole

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  Mol Ther Nucleic Acids. 2020 Mar 6;19:1198-1208.

  lncRNA RMST Suppressed GBM Cell Mitophagy through Enhancing FUS SUMOylation
  MG132 purchased from AbMole

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  Aging (Albany NY). 2020 Jul 17;12(14):14699-14717.

  Acetylation-mediated degradation of HSD17B4 regulates the progression of prostate cancer
  MG132 purchased from AbMole

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  Oncogene. 2020 Apr;39(15):3163-3178.

  The EGFR-ZNF263 Signaling Axis Silences SIX3 in Glioblastoma Epigenetically
  MG132 purchased from AbMole

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  Front Cell Infect Microbiol. 2020 Apr 16;10:158.

  Difluoromethylornithine, a Decarboxylase 1 Inhibitor, Suppresses Hepatitis B Virus Replication by Reducing HBc Protein Levels
  MG132 purchased from AbMole

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  Mol Ther Nucleic Acids. 2020 Mar 6;19:1198-1208.

  lncRNA RMST Suppressed GBM Cell Mitophagy through Enhancing FUS SUMOylation.
  MG132 purchased from AbMole

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  New Phytol. 2020 Jan;225(1):250-267.

  Phospho-mutant activity assays provide evidence for alternative phospho-regulation pathways of the transcription factor FER-LIKE IRON DEFICIENCY-INDUCED TRANSCRIPTION FACTOR.
  MG132 purchased from AbMole

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  Cell Microbiol. 2020 Mar;22(3):e13148.

  Hepatitis B virus X protein modulates upregulation of DHX9 to promote viral DNA replication.
  MG132 purchased from AbMole

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  Oncology Letters. 2019 Feb 8.

  Inhibition of the PI3K/AKT signaling pathway sensitizes diffuse large B‑cell lymphoma cells to treatment with proteasome inhibitors via suppression of BAG3.
  MG132 purchased from AbMole

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  Curr Biol. 2018 Aug 20;28(16):2616-2623.e5.

  Chloroplast Biogenesis Controlled by DELLA-TOC159 Interaction in Early Plant Development.
  MG132 purchased from AbMole

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  Oncotarget. 2018 Feb;9(12):10470-10482.

  The hypoxia-responsive lncRNA NDRG-OT1 promotes NDRG1 degradation via ubiquitin-mediated proteolysis in breast cancer cells.
  MG132 purchased from AbMole

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  J Hematol Oncol. 2017 Jun 8;10(1):115.

  SIX3, a tumor suppressor, inhibits astrocytoma tumorigenesis by transcriptional repression of AURKA/B
  MG132 purchased from AbMole

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  Autophagy. 2017 Mar 4;13(3):538-553.

  Acetylation targets HSD17B4 for degradation via the CMA pathway in response to estrone
  MG132 purchased from AbMole

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  Eur Respir J. 2015 Jun;1590-602.

  Deleterious impact of Pseudomonas aeruginosa on cystic fibrosis transmembrane conductance regulator function and rescue in airway epithelial cells.
  MG132 purchased from AbMole

Customer Product Validations & Biological Datas

	Source	New Phytol (2020 Jan). Figure 7. MG132 (Abmole Bioscience, Houston, TX, USA)
	Method	Quantitative cell-free degradation assay
	Cell Lines	tobacco leaf epidermis cells
	Concentrations	100 μM
	Incubation Time	0, 60, 120 and 240 min
	Results	Proteasomal inhibitor MG132 antagonized this degradation and confirmed proteasomal involvement in FIT protein turnover.

	Source	Current Biology (2018). Figure 3. MG132 (Abmole Bioscience)
	Method	In vivo CoIP
	Cell Lines	Total protein
	Concentrations	20 mM
	Incubation Time	12 h
	Results	PAC-treated WT seedlings incubated with MG132 (a proteasome inhibitor) had increased TOC159 levels, implicating degradation by the UPS.

	Source	Oncotarget (2018 Feb). Figure5. MG132 (Abmole Bioscience, Houston, USA)
	Method	Co-immunoprecipitation
	Cell Lines	MCF-7 cells
	Concentrations	20 μM
	Incubation Time	4 h
	Results	When MCF-7 & SKBR3 cells were treated with both cycloheximide and MG132, a proteasome inhibitor, NDRG1-OT1_v4 no longer promoted NDRG1 degradation

	Source	Journal of Hematology & Oncology (2017). Figure 5. MG132 (Abmole Bioscience)
	Method	Immunofluorescence analysis
	Cell Lines	U251, U87 and U118 cell lines
	Concentrations	20 μM
	Incubation Time	2 h
	Results	Astrocytoma patients with a low expression of SIX3 and mutant p53 are more sensitive to treatment with aurora kinase inhibitors.

	Source	Journal of Hematology & Oncology (2017). Figure 3. MG132 (Abmole Bioscience)
	Method	Western blotting
	Cell Lines	U251, U87 and U118 cell lines
	Concentrations	20 μM
	Incubation Time	2 h
	Results	When we knocked down AURKA, MG132 resulted in increased AURKB expression and had less effect on AURKA (Fig. 3e).

	Source	Institut für Biochemie der Universität Stuttgart (2014). Figure 21. MG132 (Abmole Bioscience)
	Method	MG-132 was dissolved in DMSO. To verify that the activity was sufficiently inhibited, peptide cleavage assays were performed.
	Cell Lines
	Concentrations	200 μM
	Incubation Time	2 h
	Results	As shown above, GST-Nup53 was immobilized on glutathione sepharose beads (Figure 21A, load, bottom lane; Coomassie blue stained gel) and incubated with equal amounts of CP or Blm10-CP. To confirm that equal amounts of proteasome were used, the loads were separated by SDS-PAGE, and the gel was subsequently stained with Coomassie blue and immunoblotted against the HA-tag of 4 (Figure 21A, load).

	Source	Faculté de Médecine (2015). Figure 5. MG132 (Abmole Bioscience)
	Method
	Cell Lines	CFBE-wt cells
	Concentrations	5 μM
	Incubation Time	18h
	Results	In fact, our data obtained in the presence of MG132 and/or cycloheximide (Fig. 4 and 5) indicated that CFTR synthesis may also be affected by PsaDM. Our study, as well as data from the literature, thus indicated that P. aeruginosa exoproducts may impact CFTR protein synthesis, degradation and trafficking/recycling to the cell membrane.

	Source	Faculté de Médecine (2015). Figure 4. MG132 (Abmole Bioscience)
	Method
	Cell Lines	CFBE-wt cells
	Concentrations	5 μM
	Incubation Time	18h
	Results	In fact, our data obtained in the presence of MG132 and/or cycloheximide (Fig. 4 and 5) indicated that CFTR synthesis may also be affected by PsaDM. Our study, as well as data from the literature, thus indicated that P. aeruginosa exoproducts may impact CFTR protein synthesis, degradation and trafficking/recycling to the cell membrane.

	Source	ERJ Express.(2015). Figure 5. MG132 (Abmole Bioscience, Kowloon, Honk Hong)
	Method	Immunoblotting
	Cell Lines	CFBE-ΔF508 and CFBE-wt cell lines
	Concentrations
	Incubation Time	18 h
	Results	To confirm that the huge accumulation of CFTR protein observed after proteasomal inhibition with MG132 (MG132+LB at 18 h) (fig. 5a and b) was secondary to newly synthesised CFTR proteins, we verified that a co treatment with CHX (MG132+CHX+LB) totally prevented CFTR accumulation.

	Source	ERJ Express.(2015). Figure 4. MG132 (Abmole Bioscience, Kowloon, Honk Hong)
	Method	Immunoblotting
	Cell Lines	CFBE-ΔF508 and CFBE-wt cell lines
	Concentrations
	Incubation Time	2 h, 8 h, 18 h
	Results	In fact, our data obtained in the presence of MG132 and/or CHX (figs 4 and 5) indicated that CFTR synthesis may also be affected by PsaDM.

	Source	Autophage (2016) . Figure 2. MG132 (Abmole BioScience, M1902)
	Method	Western blot
	Cell Lines	HEK293T, MCF7 or MDA-MB-231 cells
	Concentrations	10 μM
	Incubation Time	6 h
	Results	Results showed that NH4Cl, but not MG132, 3-MA or wortmannin, induced the accumulation of HSD17B4 protein (Fig. 2A ), indicating that the degradation of HSD17B4 is independent of the proteasome and macroautophagy pathways.

Protocol (for reference only)

Cell Experiment
Cell lines	Lung cancer cell lines A549 and H1299
Preparation method	Cell viability assay. Cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cells were seeded in 96-well plates at a density of 2.5x103/well 1 day prior to treatment. Then, cells were treated with MG132 or/and irradiation. After treatment, 20 µl of 5 mg/ml MTT solution was added into each well and incubated for 4 h. After the supernatant was removed, 100 µl of DMSO was added, and then placed in a microplate reader to measure OD value. Cell viability rate (vR) was calculated according to the following formula: vR = (OD in observed group/OD in 0 Gy group) x 100%. All assays were repeated 3 times in quintuplicate.
Concentrations	200 nM
Incubation time	6h

Animal Experiment
Animal models	Male mdx (C57BL/10ScSn DMD mdx) mice
Formulation	Dissolved in DMSO, and diluted in PBS
Dosages	~10 μg/kg/day
Administration	Injection

Chemical Information

Molecular Weight	475.62
Formula	C26H41N3O5
CAS Number	133407-82-6
Solubility (25°C)	DMSO 80 mg/mL Ethanol 20 mg/mL
Storage	Powder          -20°C   3 years ;  4°C   2 years In solvent       -80°C   6 months ;  -20°C   1 month

Conversion of different model animals based on BSA (PMID: 27057123)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Andrew Sandstrom, et al. Science. Functional degradation: A mechanism of NLRP1 inflammasome activation by diverse pathogen enzymes

[2] Ashley J Chui, et al. Science. N-terminal degradation activates the NLRP1B inflammasome

[3] Guo N, et al. Asia Pac J Clin Oncol. MG132, a proteasome inhibitor, induces apoptosis in tumor cells.

[4] Zanotto-Filho A, et al. Invest New Drugs. Proteasome inhibitor MG132 induces selective apoptosis in glioblastoma cells through inhibition of PI3K/Akt and NFkappaB pathways, mitochondrial dysfunction, and activation of p38-JNK1/2 signaling.

[5] Han YH, et al. Oncol Rep. The effect of MG132, a proteasome inhibitor on HeLa cells in relation to cell growth, reactive oxygen species and GSH.