MG132 蛋白酶体抑制剂

生物活性

MG-132是一种蛋白酶体抑制剂，IC50为100 nM，也抑制钙蛋白酶，IC50为1.2 μM。MG132通过诱导细胞周期停滞以及引发细胞凋亡来抑制HeLa细胞的生长。MG-132 (10 μM) 通过抑制蛋白酶体介导的IκBα降解，有效抑制A549细胞中TNF-α诱导的NF-κB活化。MG132可以抑制NLRP1的活化。

体内研究中，MG-132（ip，0.1 mg/kg/day）通过调节ERK1/2和JNK1信号通路，减轻压力超负荷引起的心脏肥大。MG-132治疗通过下调肌肉特异性泛素连接酶atrogin-1/MAFbx 和MuRF-1 mRNA，显著减少小鼠体内固定化诱导的骨骼肌萎缩。

使用AbMole产品发表的文献

• J Inflamm Res. 2023 Feb 27;16:861-877.

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• Cell Death Discov. 2023 Apr 26.

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• FASEB J. 2023 May;37(5):e22931.

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• World J Gastroenterol. 2023 Sep 21;29(35): 5104-5124.

  Regenerating gene 4 promotes chemoresistance of colorectal cancer by affecting lipid droplet synthesis and assembly

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

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

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

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

• 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

• 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

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

  UBE2B promotes ovarian cancer growth via promoting RAD18 mediated ZMYM2 monoubiquitination and stabilization

• 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

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

  MG132 protects against lung injury following brain death in rats

• 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

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

  USP14 maintains HIF1-α stabilization via its deubiquitination activity in hepatocellular carcinoma

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

  Essential role of zyxin in platelet biogenesis and glycoprotein Ib-IX surface expression

• 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

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

  Autophagy Mediates the Degradation of Plant ESCRT Component FREE1 in Response to Iron Deficiency

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

  N6-methyladenosine regulates ATM expression and downstream signaling

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

  The EGFR-ZNF263 Signaling Axis Silences SIX3 in Glioblastoma Epigenetically

• 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.

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

  lncRNA RMST Suppressed GBM Cell Mitophagy through Enhancing FUS SUMOylation

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

  lncRNA RMST Suppressed GBM Cell Mitophagy through Enhancing FUS SUMOylation.

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

  Acetylation-mediated degradation of HSD17B4 regulates the progression of prostate cancer

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

  Hepatitis B virus X protein modulates upregulation of DHX9 to promote viral DNA replication.

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

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

• 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.

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

  Chloroplast Biogenesis Controlled by DELLA-TOC159 Interaction in Early Plant Development.

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

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

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

  Acetylation targets HSD17B4 for degradation via the CMA pathway in response to estrone

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

  SIX3, a tumor suppressor, inhibits astrocytoma tumorigenesis by transcriptional repression of AURKA/B

• 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.

产品使用成果展示

	数据来源	New Phytol (2020 Jan). Figure 7. MG132 (Abmole Bioscience, Houston, TX, USA)
	方法	Quantitative cell-free degradation assay
	细胞系/动物模型	tobacco leaf epidermis cells
	浓度	100 μM
	处理时间	0, 60, 120 and 240 min
	实验结果	Proteasomal inhibitor MG132 antagonized this degradation and confirmed proteasomal involvement in FIT protein turnover.

	数据来源	Current Biology (2018). Figure 3. MG132 (Abmole Bioscience)
	方法	In vivo CoIP
	细胞系/动物模型	Total protein
	浓度	20 mM
	处理时间	12 h
	实验结果	PAC-treated WT seedlings incubated with MG132 (a proteasome inhibitor) had increased TOC159 levels, implicating degradation by the UPS.

	数据来源	Oncotarget (2018 Feb). Figure5. MG132 (Abmole Bioscience, Houston, USA)
	方法	Co-immunoprecipitation
	细胞系/动物模型	MCF-7 cells
	浓度	20 μM
	处理时间	4 h
	实验结果	When MCF-7 & SKBR3 cells were treated with both cycloheximide and MG132, a proteasome inhibitor, NDRG1-OT1_v4 no longer promoted NDRG1 degradation

	数据来源	Journal of Hematology & Oncology (2017). Figure 5. MG132 (Abmole Bioscience)
	方法	Immunofluorescence analysis
	细胞系/动物模型	U251, U87 and U118 cell lines
	浓度	20 μM
	处理时间	2 h
	实验结果	Astrocytoma patients with a low expression of SIX3 and mutant p53 are more sensitive to treatment with aurora kinase inhibitors.

	数据来源	Journal of Hematology & Oncology (2017). Figure 3. MG132 (Abmole Bioscience)
	方法	Western blotting
	细胞系/动物模型	U251, U87 and U118 cell lines
	浓度	20 μM
	处理时间	2 h
	实验结果	When we knocked down AURKA, MG132 resulted in increased AURKB expression and had less effect on AURKA (Fig. 3e).

	数据来源	Institut für Biochemie der Universität Stuttgart (2014). Figure 21. MG132 (Abmole Bioscience)
	方法	MG-132 was dissolved in DMSO. To verify that the activity was sufficiently inhibited, peptide cleavage assays were performed.
	细胞系/动物模型
	浓度	200 μM
	处理时间	2 h
	实验结果	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).

	数据来源	Faculté de Médecine (2015). Figure 5. MG132 (Abmole Bioscience)
	方法
	细胞系/动物模型	CFBE-wt cells
	浓度	5 μM
	处理时间	18h
	实验结果	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.

	数据来源	Faculté de Médecine (2015). Figure 4. MG132 (Abmole Bioscience)
	方法
	细胞系/动物模型	CFBE-wt cells
	浓度	5 μM
	处理时间	18h
	实验结果	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.

	数据来源	ERJ Express.(2015). Figure 5. MG132 (Abmole Bioscience, Kowloon, Honk Hong)
	方法	Immunoblotting
	细胞系/动物模型	CFBE-ΔF508 and CFBE-wt cell lines
	浓度
	处理时间	18 h
	实验结果	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.

	数据来源	ERJ Express.(2015). Figure 4. MG132 (Abmole Bioscience, Kowloon, Honk Hong)
	方法	Immunoblotting
	细胞系/动物模型	CFBE-ΔF508 and CFBE-wt cell lines
	浓度
	处理时间	2 h, 8 h, 18 h
	实验结果	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.

	数据来源	Autophage (2016) . Figure 2. MG132 (Abmole BioScience, M1902)
	方法	Western blot
	细胞系/动物模型	HEK293T, MCF7 or MDA-MB-231 cells
	浓度	10 μM
	处理时间	6 h
	实验结果	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.

实验参考

体外实验*
细胞系	Lung cancer cell lines A549 and H1299
方法	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.
浓度	200 nM
处理时间	6h

*上述方法来自公开文献，仅供相同目的实验参考。如实验目的、材料、方法不同，请参考其他文献。

体内实验*
动物模型	Male mdx (C57BL/10ScSn DMD mdx) mice
配制	Dissolved in DMSO, and diluted in PBS
剂量	~10 μg/kg/day
给药处理	Injection

*上述方法来自公开文献，仅供相同目的实验参考。如实验目的、材料、方法不同，请参考其他文献。

化学性质

分子量	475.62
分子式	C26H41N3O5
CAS号	133407-82-6
溶解性（25°C）	DMSO 80 mg/mL Ethanol 20 mg/mL
储存条件	粉末型式       -20°C   3年；4°C   2年 溶于溶剂       -80°C   6个月；-20°C   1个月
运输方式	冰袋运输，根据产品的不同，可能会有相应调整。

储备液配制

*下述溶液配置方法仅为基于分子量计算出的理论值。不同产品在配置溶液前，需考虑其在不同溶剂中的溶解度限制。

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	2.1025 mL	10.5126 mL	21.0252 mL
5 mM	0.4205 mL	2.1025 mL	4.205 mL
10 mM	0.2103 mL	1.0513 mL	2.1025 mL

不同实验动物依据体表面积的等效剂量转换表（参考来源于公开文献）

	小鼠	大鼠	兔	豚鼠	仓鼠	狗
重量 (kg)	0.02	0.15	1.8	0.4	0.08	10
体表面积 (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km 系数	3	6	12	8	5	20

动物 A (mg/kg) = 动物 B (mg/kg) ×	动物 B的Km系数
	动物 A的Km系数

例如，依据体表面积折算法，将化合物用于小鼠的剂量20 mg/kg 换算成大鼠的剂量，需要将20 mg/kg 乘以小鼠的K_m系数（3），再除以大鼠的K_m系数（6），得到化合物用于大鼠的等效剂量为10 mg/kg。

参考文献

[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.