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Chemical Structure| 133407-82-6 Chemical Structure| 133407-82-6

Structure of MG-132
CAS No.: 133407-82-6

Chemical Structure| 133407-82-6

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MG-132 is an inhibitor of proteasome (IC50 = 100 nM) and calpain (IC50 = 1.2 nM).

Synonyms: Z-Leu-Leu-Leu-al; Z-Leu-Leu-Leu-CHO; MGI-132

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Product Citations

Product Citations      Show More

Jiang, Huaji ; Xie, Yingchao ; Hu, Zhiqiang ; Lu, Jiansen ; Zhang, Jiahuan ; Li, Hongyu , et al.

Abstract: Inflammatory bowel disease (IBD) is a chronic and potentially life-threatening inflammatory disease of gastroenteric tissue characterized by episodes of intestinal inflammation, but the underlying mechanisms remain elusive. Here, we explore the role and precise mechanism of VanGogh-like 2 (VANGL2) during the pathogenesis of IBD. VANGL2 decreases in IBD patients and dextran sulfate sodium (DSS)-induced colitis in mice. Myeloid VANGL2 deficiency exacerbates the progression of DSS-induced colitis in mice and specifically enhances the activation of NLRP3 inflammasome in macrophages. NLRP3-specific inhibitor MCC950 effectively alleviates DSS-induced colitis in VANGL2 deficient mice. Mechanistically, VANGL2 interacts with NLRP3 and promotes the autophagic degradation of NLRP3 through enhancing the K27-linked polyubiquitination at lysine 823 of NLRP3 by recruiting E3 ligase MARCH8, leading to optineurin (OPTN)-mediated selective autophagy. Notably, decreased VANGL2 in the peripheral blood mononuclear cells from IBD patients results in overt NLRP3 inflammasome activation and sustained inflammation. Taken together, this study demonstrates that VANGL2 acts as a repressor of IBD progression by inhibiting NLRP3 inflammasome activation and provides insights into the crosstalk between inflammation and autophagy in preventing IBD.

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Zhiqiang Hu ;  Yufen Zhang ;  Yingchao Xie ;  Jianwu Yang ;  Haotian Tang ;  Bolin Fan , et al.

Abstract: Toxoplasma gondii (T. gondii)-associated polymorphic effector proteins are crucial in parasite development and regulating host anti-T. gondii immune responses. However, the mechanism remains obscure. Here, it is shown that Toxoplasma effector dense granules 4 (GRA4) restricts host IFN-I activation. Infection with ∆gra4 mutant T. gondii strain induces stronger IFN-I responses and poses a severe threat to host health. Mechanistically, GRA4 binds to phosphorylated TBK1 to promote TRIM27-catalyzed K48-ubiquitination at Lys251/Lys372 residues, which enhances its recognition by receptor p62, ultimately leading to TBK1 autophagic degradation. Furthermore, an avirulent ∆gra4 strain (ME49∆ompdc/gra4) is constructed for tumor immunotherapy due to its ability to enhance IFN-I production. Earlier vaccination with ME49∆ompdc/gra4 confers complete host resistance to the tumor compared with the classical ME49∆ompdc treatment. Notably, ME49∆ompdc/gra4 vaccination induces a specific CD64 +MAR-1 +CD11b + dendritic cell subset, thereby enhancing T cell responses. Overall, these findings identify the negative role of T. gondii GRA4 in modulating host IFN-I signaling and suggest that GRA4 can be a potential target for the development of T. gondii vaccines and tumor immunotherapy.

Keywords: attenuated T. gondii ; selective autophagy ; toxoplasmosis ; tumor therapy ; type I interferon

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Alternative Products

Product Details of MG-132

CAS No. :133407-82-6
Formula : C26H41N3O5
M.W : 475.62
SMILES Code : O=C(OCC1=CC=CC=C1)N[C@@H](CC(C)C)C(N[C@@H](CC(C)C)C(N[C@@H](CC(C)C)C=O)=O)=O
Synonyms :
Z-Leu-Leu-Leu-al; Z-Leu-Leu-Leu-CHO; MGI-132
MDL No. :MFCD00674886
InChI Key :TZYWCYJVHRLUCT-VABKMULXSA-N
Pubchem ID :462382

Safety of MG-132

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
MEFs 10 µM 1 h MG132 was used to inhibit the proteasome activity, leading to analysis of STING pathway activation. PMC9666523
MNs 1 μM 48 h To explore the role of GSDME in motor neuron injury PMC10121894
HEK293-EBNA 10 µM 24 h The treatment was used to assess the effects on ubiquitination assays. PMC9440122
Primary schwannoma cells 10 µM 3 h Monitor proteasoma-dependent degradation. PMC10115179
PDCCs 4 µM 6 days MG-132 was used as a positive control for cell survival. PMC9353492
293T cells 20 μM 7 h To detect ubiquitination of proteins PMC7854732
TuBo mammospheres 10 µM 8 h To analyze the effect of MG132 on protein extraction from mammospheres. PMC10175288
HEK293 cells 20, 40, 80 μM 4 h Induction of proteasome stress PMC8172468
iPSC derived cardiomyocytes 10 μM 3 h Assess the effects of MG132 on hypoxia treatment in cardiomyocytes. PMC8961225
A172 10 μM 6 h to suppress proteasome-mediated protein degradation PMC9468590
HCT116, RKO 20 μM 6 h To analyze the ubiquitination of proteins involved in NF-κB signaling. PMC10850134
CS cells 10 μM 8 h To analyze the expression of proteins; results showed significant differences based on statistical analysis. PMC8257592
293T cells and NP cells 10 μm 8 h The goal was to analyze GPX4 ubiquitination. This experimentation is implied but not explicitly detailed in the effects. PMC10161035
HeLa cells 10 μM 6h Explore the impact of MG132 on MARVELD1 and PARP1 interactions PMC10070477
293T cells 10μm 48 h MG132 is used to inhibit proteasome degradation and help determine the degradation pathway of mHTT. PMC10625127
GIST cells 20 μm 8 h To analyze the protein levels of USP5 and TRIM21. PMC11425886
Jurkat cells 50 μm 8 h To assess the degradation efficiency of PROTAC toolbox on targeted proteins. PMC11220716
HCT116, HT29 1 μM 24 h To evaluate the effect of TKD on KRAS degradation in cancer cells. PMC11211324
HepG2 20 μM 6 h To examine the ubiquitination of exogenous p53 protein. PMC8386927
MDA-MB-231 10 μM 6 h MG132 was used to assess its effect on Vimentin expression and ubiquitination. PMC7851937
HEK293T cells 10 µM 6 h PMC9883464
HGPS iPSC-derived VSMC 1.25 µM 24 h MG-132 treatment significantly reduced progerin expression levels. PMC5582415
HGPS fibroblasts 5 µM 24 h MG-132 treatment significantly reduced progerin levels and promoted its degradation through autophagy. PMC5582415
HepG2 cells 0.3 μM 24 h Long-term treatment did not change LDLR mRNA but significantly increased LDLR protein by reducing PCSK9-mediated lysosome LDLR degradation. PMC4125719
HepG2 cells 0.3 μM 8 h Short-term treatment significantly increased LDLR mRNA and protein levels, which was blocked by PKC inhibitors. PMC4125719
HepG2 cells 0.03–3 μM 24 h MG132 dose-dependently increased LDLR mRNA and protein levels, as well as LDL uptake. PMC4125719
HeLa cells 10 µM 16 hours To evaluate the effect of Delanzomib on the plasma membrane expression of pathogenic pendrin variants. Results showed that Delanzomib significantly increased the plasma membrane expression levels of pathogenic pendrin variants. PMC11913434
293 Phoenix cells 1-10 µM 16 hours To evaluate the rescue effect of Delanzomib on the protein expression and ion transport function of pathogenic pendrin variants. Results showed that Delanzomib significantly increased the total protein levels and ion transport function of pathogenic pendrin variants. PMC11913434
HEK293T cells 10 µM 6 hours Proteasome inhibition MG132 stabilized PD-L1 during gallic acid treatment PMC9274539

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice BALB/c nude mice Subcutaneous injection 10 mg/kg weekly To evaluate the effect of MG132 on tumor formation PMC9596831
Mice LmnaG609G/G609G mouse model Intramuscular injections 1 µg/kg and 10 µg/kg Three times per week for 2 weeks Local injection of MG-132 significantly reduced progerin and SRSF-1 levels without noticeable side effects. PMC5582415

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.10mL

0.42mL

0.21mL

10.51mL

2.10mL

1.05mL

21.03mL

4.21mL

2.10mL

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