(R)-MG132
(Synonyms: N-[(苯基甲氧基)羰基]-L-亮氨酰-N-[(1S)-1-甲酰基-3-甲基丁基]-D-亮氨酰胺,(S,R,S)-(-)-MG-132; Z-Leu-D-Leu-Leu-al) 目录号 : GC41233
(R)-MG132是一种蛋白酶体抑制剂，IC50为100 nM。
Cas No.:1211877-36-9
Sample solution is provided at 25 µL, 10mM.
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Related Biological Data
Penetration efficiency of peptide KKP.(E) Fluorescence intensity quantification of FITC-labeled KKP1 (7.5 μM) treated with different time points (with or without the MG132 treatment) corresponding to the fluorescence microscopy shown in(D).
(R)-MG132 (GC41233) was obtained from GLPBIO (Montclair,CA, USA).
Acs Pharmacol Transl 6.1 (2022): 76-87. PMID: 36654751 IF: 5.9998 -
Related Biological Data
HNK increases protein ubiquitination by inhibiting proteasome activity. e NB4 cells were treated with HNK (0 or 30 μM) for 24 h, and the cells were collected for 20S protease activity determination. 1 μM (R)-MG-132 was used as a positive control.
In the presence or absence of (R)-MG-132(1 μM)(GLPBIO), the same amount of 30 μg protein, 20 μM fluorescent substrate (Suc-Leu-Leu-Val-Tyr-AMC) and a proper amount of buffer were distributed into a black 96-well plate with transparent substrate.
Apoptosis (2021): 1-14. PMID: 33550458 IF: 4.67
Quality Control & SDS
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- Purity: >98.00%
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- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
Cell lines | Rat C6 glioma cells |
Preparation Method | Cells were seeded onto 96-well microplates and cultured for 24 hours. Subsequently, the cells were treated with (R)-MG132 at final concentrations ranging from 10 to 40 μM for durations of 3 to 24 hours. |
Reaction Conditions | 10-μM ; 3-24h |
Applications | (R)-MG132 inhibited the proliferation of C6 glioma cells in a time- and dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | Male BALB/c mice (CVB3 cell induced acute viral myocarditis models) |
Preparation Method | Mice were administered (R)-MG132 intraperitoneally on a daily basis starting the day after CVB3 inoculation. |
Dosage form | 10μg/kg; i.p; daily for 7days |
Applications | (R)-MG132 demonstrates anti-apoptotic and anti-inflammatory properties in the context of myocardial injuries induced by CVB3. |
References: [1]:Fan WH, Hou Y,et,al. Proteasome inhibitor MG-132 induces C6 glioma cell apoptosis via oxidative stress. Acta Pharmacol Sin. 2011 May;32(5):619-25. doi: 10.1038/aps.2011.16. Epub 2011 Apr 18. PMID: 21499287; PMCID: PMC4002511. [2]:Zhang XM, Li YC, et,al. MG-132 attenuates cardiac deterioration of viral myocarditis via AMPK pathway. Biomed Pharmacother. 2020 Jun;126:110091. doi: 10.1016/j.biopha.2020.110091. Epub 2020 Apr 8. PMID: 32278272. | |
(R)-MG132 is a proteasome inhibitor with an IC50 of 100 nM. This compound effectively hinders the proteolytic function of the 26S proteasome complex, leading to induced autophagy and apoptosis. Moreover, (R)-MG132 exhibits notable efficacy in inhibiting tumor growth[1-2].
(R)-MG132(10- 40 μM ; 3-24h) suppressed the proliferation of C6 glioma cells and also inhibited the chymotrypsin-like activity of the proteasome[3]. (R)-MG132(1 μM;24h) triggers the nuclear translocation of AIF by down-regulating the ERK and Akt/mTOR pathways[4]. The combination of GSK-470 and (R)-MG132 (200 nM; 24 hours) leads to nearly complete inhibition of AKT activity and mTORC1/mTORC2 activity[5].
(R)-MG132(10μg/kg; i.p; daily for 7days) regulated the AMPK signaling pathway, thereby modulating apoptosis and inflammation, enhancing hemodynamics, and inhibiting ventricular structural remodeling in a myocarditis mouse model [6]. Treatment with (R)-MG132(0.1mg/kg; i.p) significantly mitigated cancer cachexia, as evidenced by reduced weight loss, altered carbohydrate metabolism, decreased muscle atrophy, increased spontaneous activity, and extended survival time in tumor-bearing mice[7].
[1]. Harhouri K, Navarro C, et.al. MG132-induced progerin clearance is mediated by autophagy activation and splicing regulation. EMBO Mol Med. 2017 Sep;9(9):1294-1313. doi: 10.15252/emmm.201607315. PMID: 28674081; PMCID: PMC5582415.
[2]. Tsubuki S, Saito Y, , et.al. Differential inhibition of calpain and proteasome activities by peptidyl aldehydes of di-leucine and tri-leucine. J Biochem. 1996 Mar;119(3):572-6. doi: 10.1093/oxfordjournals.jbchem.a021280. PMID: 8830056.
[3]. Fan WH, Hou Y, , et.al. Proteasome inhibitor MG-132 induces C6 glioma cell apoptosis via oxidative stress. Acta Pharmacol Sin. 2011 May;32(5):619-25. doi: 10.1038/aps.2011.16. Epub 2011 Apr 18. PMID: 21499287; PMCID: PMC4002511.
[4]. Ko JK, Choi CH, , et.al. The proteasome inhibitor MG-132 induces AIF nuclear translocation through down-regulation of ERK and Akt/mTOR pathway. Neurochem Res. 2011 May;36(5):722-31. doi: 10.1007/s11064-010-0387-9. Epub 2011 Jan 4. PMID: 21203833.
[5]. Zhang J, Yang C, , et.al. PDK1 inhibitor GSK2334470 synergizes with proteasome inhibitor MG‑132 in multiple myeloma cells by inhibiting full AKT activity and increasing nuclear accumulation of the PTEN protein. Oncol Rep. 2018 Jun;39(6):2951-2959. doi: 10.3892/or.2018.6369. Epub 2018 Apr 12. PMID: 29658600.
[6]. Zhang XM, Li YC, et.al. MG-132 attenuates cardiac deterioration of viral myocarditis via AMPK pathway. Biomed Pharmacother. 2020 Jun;126:110091. doi: 10.1016/j.biopha.2020.110091. Epub 2020 Apr 8. PMID: 32278272.
[7]. Zhang L, Tang H, et.al. MG132-mediated inhibition of the ubiquitin-proteasome pathway ameliorates cancer cachexia. J Cancer Res Clin Oncol. 2013 Jul;139(7):1105-15. doi: 10.1007/s00432-013-1412-6. Epub 2013 Mar 28. PMID: 23535871; PMCID: PMC7087863.
(R)-MG132是一种蛋白酶体抑制剂，IC50为100 nM。该化合物有效阻碍26S蛋白酶体复合物的蛋白水解，导致诱导自噬和凋亡。(R)-MG132具有显著的抑制肿瘤生长的作用[1-2]。
(R)-MG132(10- 40 μM ; 3-24h)抑制C6胶质瘤细胞的增殖，并抑制蛋白酶体的凝乳胰蛋白酶样活性[3]。(R)-MG132(1 μM;24h)通过下调ERK和Akt/mTOR通路触发AIF的核易位[4]。GSK-470和(R)-MG132(200 nM; 24 hours)的结合导致AKT活性和mTORC1/mTORC2活性几乎完全抑制[5]。
在心肌炎小鼠模型中，(R)-MG132(10μg/kg; i.p; daily for 7days)调节AMPK信号通路，从而调节细胞凋亡和炎症，增强血流动力学，抑制心室结构重构[6]。(R)-MG132(0.1mg/kg; i.p)治疗可显著减轻肿瘤恶病质，荷瘤小鼠体重减轻、碳水化合物代谢改变、肌肉萎缩减少、自发活动增加和生存时间延长[7]。
| Cas No. | 1211877-36-9 | SDF | |
| 别名 | N-[(苯基甲氧基)羰基]-L-亮氨酰-N-[(1S)-1-甲酰基-3-甲基丁基]-D-亮氨酰胺,(S,R,S)-(-)-MG-132; Z-Leu-D-Leu-Leu-al | ||
| Canonical SMILES | O=CC[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)OCc1ccccc1 | ||
| 分子式 | C26H41N3O5 | 分子量 | 475.6 |
| 溶解度 | DMF: 30 mg/ml,DMSO: 30 mg/ml,Ethanol: 25 mg/ml | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1026 mL | 10.513 mL | 21.0261 mL |
| 5 mM | 0.4205 mL | 2.1026 mL | 4.2052 mL |
| 10 mM | 0.2103 mL | 1.0513 mL | 2.1026 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
FBXO22 promotes the development of hepatocellular carcinoma by regulating the ubiquitination and degradation of p21
J Exp Clin Cancer Res 2019 Feb 26;38(1):101.PMID:30808376DOI:10.1186/s13046-019-1058-6.
Background: Deregulation of ubiquitin ligases is related to the malignant progression of human cancers. F-box only protein 22 (FBXO22), an F-box E3 ligase, is a member of the F-box protein family. However, the biological function of FBXO22 in HCC and the underlying molecular mechanisms are still unclear. In this study, we explored the role of FBXO22 in HCC and its mechanism of promoting tumor development. Methods: We examined the expression of FBXO22 in normal liver cell lines, HCC cell lines, HCC tissue microarrays and fresh specimens. The correlation between FBXO22 and clinical features was analyzed in a retrospective study of 110 pairs of HCC tissue microarrays. Univariate and multivariate survival analyses were used to explore the prognostic value of FBXO22 in HCC. At the same time, the correlation between the FBXO22 and p21 was also studied in HCC samples. Knock-down and overexpression experiments, CHX and Mg132 intervention experiments, ubiquitination experiments, rescue experiments and nude mouse xenograft models were used to determine the potential mechanism by which FBXO22 promotes tumorigenesis in vitro and in vivo. Results: The expression of FBXO22 in HCC tissues was significantly higher than in normal liver tissues. The overall survival rate and disease-free survival time of patients with high expression of FBXO22 were significantly shorter than those of patients with low expression of FBXO22. The high expression of FBXO22 in HCC tissues were significantly correlated with serum AFP (p = 0. 003, Pearson's chi-squared test), tumor size (p = 0. 019, Pearson's chi-squared test) and vascular invasion (p = 0. 031, Pearson's chi-squared test). Especially, Multivariate analysis showed that tumor size and the expression of FBXO22 were independent prognostic indicator of OS (95% CI: 1.077-5.157, P<0.05). Correlation analysis also showed that FBXO22 was negatively correlated with p21 in tissue microarrays (R = - 0.3788, P<0.001, Pearson correlation) and fresh specimens (R = - 0.4037, P<0.01, Pearson correlation). Moreover, both in vitro and in vivo experiments showed that knocking down FBXO22 expression could inhibit cell proliferation, while overexpression of FBXO22 promoted tumor formation. Furthermore, we identified that FBXO22 interacts with p21 by regulating protein stability and by influencing the ubiquitination process. A knockdown of FBXO22 decreased the ubiquitylation of p21, while overexpression enhanced it. Conclusions: This study uncovered a new mechanism by which FBXO22 functions as an oncogene in HCC pathogenesis and progression by mediating the ubiquitination and degradation of p21. It was also found that tumor size and the expression of FBXO22 were independent prognostic indicator of OS and the expression of FBXO22 and p21 was negatively correlated in clinical samples. Our findings present a new perspective for understanding the development of HCC, which may provide a new target for the treatment and management of this challenging cancer.
MG132 protects against lung injury following brain death in rats
Exp Ther Med 2022 Sep 23;24(5):687.PMID:36277154DOI:10.3892/etm.2022.11623.
Brain death (BD) results in injury to organs and induces lung donor dysfunction. Since the 20S proteasome abnormality is associated with a variety of diseases, the present study investigated whether it was involved in lung injury following BD in rats, and the effects of the proteasome inhibitor MG132 on lung injury was also assessed. Rats were assigned to a BD group or a control sham group. The BD group of rats were sacrificed at different time points after BD. Administration of MG132 was performed intraperitoneally 30 min before BD. Arterial blood was drawn to measure the oxygenation index [partial artery pressure of oxygen (PaO2)/fractional concentration of inspired oxygen (FiO2)]. The right lung was used for staining with hematoxylin and eosin, immunohistochemistry, immunofluorescence, western blotting and RT-qPCR analysis. The left lung was used to measure the wet and dry weights. Rat alveolar macrophages (NR8383) were treated with MG132 and hypoxia/reoxygenation (H/R) and used for western blotting and flow cytometry. The PaO2/FiO2 ratio decreased after BD; the wet/dry weight ratio, histological lung injury score and protein expression of 20S proteasome β1 and inducible nitric oxide synthase (iNOS) gradually increased in rats after BD. Colocalization in the immunofluorescence between 20S proteasome β1 and iNOS was observed. MG132 treatment increased the PaO2/FiO2 ratio and decreased the wet/dry weight ratio, histological lung injury score and protein expression of 20S proteasome β1 and iNOS in rats after BD. MG132 was revealed to increase NR8383 apoptosis after H/R and to upregulate the protein expression levels of p-JNK and cleaved-caspase 3. Overall, the proteasome inhibitor MG132 could effectively reduce lung injury, which may be associated with its ability to inhibit the expression of the proteasome and promote the apoptosis of alveolar macrophages.
MG132 alleviates liver injury induced by intestinal ischemia/reperfusion in rats: involvement of the AhR and NFκB pathways
J Surg Res 2012 Jul;176(1):63-73.PMID:22079846DOI:10.1016/j.jss.2011.09.001.
Background: MG132 is a potent antioxidant and has been reported to play a protective role in ischemia/reperfusion (I/R) of many organs. Recent studies have shown that the Aryl hydrocarbon receptor (AhR) may play a beneficial role in I/R of many organs and an AhR agonist has been implicated in an anti-inflammatory role. MG132 might function as an AhR agonist through proteasome inhibition, possibly through the inhibition of NFκB. Herein, we hypothesized that MG132 may play a protective role in liver injury induced by intestinal I/R and we analyzed the expression behavior of AhR and NFκB to determine whether the two factors play a role in intestinal I/R. Materials and methods: Thirty-two Sprague-Dawley rats were divided into four groups: control, I/R, MG132 control, and MG132 pretreatment. The I/R and MG132 pretreatment groups were subjected to mesenteric arterial ischemia for 1 h and reperfusion for 3 h. The control and MG132 control groups underwent surgical preparation including isolation of the superior mesenteric artery (SMA) without occlusion. The MG132 control and MG132 pretreatment groups were subjected to intraperitoneal administration of 0.5 mg/kg MG132 30 min before surgery. We collected serum specimens to measure TNF-α, IL-6, liver tissue levels of malondialdehyde (MDA), AhR, and cyp1a2; NFκB, IκBα, and ICAM-1 were also tested. Histologic changes of liver and intestine were subsequently evaluated. Results: Compared with the control group, significant increases in MDA, NFκB, and ICAM-1 levels were accompanied by decreases in AhR, cyp1a2, and IκBα expression in the liver in the I/R group, which is consistent with liver and intestinal tissue injury. MG132 blocked the alterations of the indicators above. There were no changes in the MG132 control group compared with the control group in the indicators above. Conclusions: This study demonstrated that MG132 has a significant effect in protection against liver injury induced by intestinal I/R, which may be due to modulation of the AhR and NFκB pathways.
The F-box protein CPR1/CPR30 negatively regulates R protein SNC1 accumulation
Plant J 2012 Feb;69(3):411-20.PMID:21967323DOI:10.1111/j.1365-313X.2011.04799.x.
Disease resistance (R) proteins, as central regulators of plant immunity, are tightly regulated for effective defense responses and to prevent constitutive defense activation under non-pathogenic conditions. Here we report the identification of an F-box protein CPR1/CPR30 as a negative regulator of an R protein SNC1 likely through SCF (Skp1-cullin-F-box) mediated protein degradation. The cpr1-2 (cpr30-1) loss-of-function mutant has constitutive defense responses, and it interacts synergistically with a gain-of function mutant snc1-1 and a bon1-1 mutant where SNC1 is upregulated. The loss of SNC1 function suppresses the mutant phenotypes of cpr1-2 and cpr1-2 bon1-1, while overexpression of CPR1 rescues mutant phenotypes of both bon1-1 and snc1-1. Furthermore, the amount of SNC1 protein is upregulated in the cpr1-2 mutant and down-regulated when CPR1 is overexpressed. The regulation of SNC1 by CPR1 is dependent on the 26S proteosome as a protease inhibitor MG132 stabilizes SNC1 and reverses the effect of CPR1 on SNC1. Interestingly, CPR1 is induced after infection of both virulent and avirulent pathogens similarly to the other negative defense regulator BON1. Thus, this study reveals a new mechanism in R protein regulation likely through protein degradation and suggests negative regulation as a critical component in fine control of plant immunity.
Poly R(C) binding protein (PCBP) 1 expression is regulated by the E3 ligase UBE4A in thyroid carcinoma
Biosci Rep 2017 Oct 31;37(5):BSR20170114.PMID:28963376DOI:10.1042/BSR20170114.
Thyroid cancer patients with high miR-490-3p inhibit translation of PCBP1 mRNA, whereas in patients with low miR-490-3p PCBP1 mRNA expression is high; however, the resultant protein is targeted for degradation through the proteasome. The objective of the present study was to evaluate the molecular mechanism that regulates post-translation degradation of poly R(C) binding protein (PCBP) 1 expression in thyroid cancer cells. Mass spectrometric analysis of PCBP1 immunoprecipitates from MG-132 treated TPC1 cells revealed a list of ubiquitin ligases associated with PCBP1. RNAi-mediated silencing of the candidate ubiquitin ligases revealed that knockdown of the ubiquitin ligase UBE4A stabilized PCBP1 in TPC1 cells. Concurrent overexpression of the candidate ubiquitin ligases in the normal thyroid epithelial cell line Nthy-ori 3-1 confirmed that ubiquitin conjugation factor E4 A (UBE4A) is the ubiquitin ligase that is degrading PCBP1. Coimmunoprecipitation of HA-tagged PCBP1 in TPC1 cells cotransfected with FLAG-UBE4A revealed robust polyubiquitinated smear of PCBP1, thus confirming UBE4A as the ubiquitin ligase of PCBP1. UBE4A expression mimicked PCBP1 mRNA expression in thyroid cancer patients and was inversely correlated to PCBP1 protein expression. Low UBE4A expression level was associated with a better prognosis in thyroid cancer patients. Our data reveal a post-translational regulatory mechanism of regulating PCBP1 expression in thyroid cancer cells.