MG-132

MG-132 (133407-82-6) is a specific inhibitor of the chymotrypsin-like activity of the 20S proteasome (IC50=100 nM with Z-LLL-AMC as substrate).1 Also inhibits calpain (IC50=1.25 μM).1 Suppresses gastric cancer cell proliferation and induces macro-autophagy.2 Activates stress kinases and induces Hsp72.3 Induces neurite outgrowth.1 MG-132 blocks NFκB activation by blocking IκB proteolysis (IC50=3 μM).4 Cell permeable.

A proteasome and NF-κB inhibitor.

MG 132 is a potent, membrane-permeable proteasome inhibitor. It induces neurite outgrowth in PC12 cells. Neuroprotective product.

ChEBI: A tripeptide that is L-leucyl-L-leucyl-L-leucine in which the C-terminal carboxy group has been reduced to the corresponding aldehyde and the N-terminal amino group is protected as its benzyloxycarbonyl derivative.

Potent, reversible, and cell-permeable proteasome inhibitor (K_i = 4 nM). Reduces the degradation of ubiquitin-conjugated proteins in mammalian cells and permeable stains of yeast by the 26S complex without affecting its ATPase or isopeptidase activities. Activates c-Jun N-terminal kinase (JNK1) and inhibits NF-κB activation (IC₅₀ = 3 μM).

Potent cell-permeable inhibitor of proteasome (IC 50 = 100 nM) and calpain (IC 50 = 1.2 μ M). Inhibits TNF- α -induced NF- κ B activation and I κ B α degradation. Induces neurite outgrowth in PC12 cells and has anticancer properties in vitro .

Cell permeable: yes

-20°C (desiccate)

MG-132 is a potent proteasome and calpain inhibitor. Research studies have shown that MG-132 prevents degradation of the proteasome substrates SucLLVY-MCA and ZLLL-MCA with an IC50 of 850 nM and 100 nM, respectively, as well as inhibits casein-degrading activity of m-calpain with an IC50 of 1.25 µM. Investigators have demonstrated that MG-132 inhibits TNF-α-induced NF-κB activation and IL-8 release in A549 cells. Proteasome inhibition with MG-132 prevents degradation of short-lived proteins, which correlates with increased expression of HSP and ER chaperone proteins. MG-132 induces apoptosis in Hep G2 cells in a time- and dose-dependent manner. Proteasome inhibitors like MG-132 are important research tools for studying cellular degradation of the ubiquitin-proteasome pathway.

[1] S TSUBUKI. Differential inhibition of calpain and proteasome activities by peptidyl aldehydes of di-leucine and tri-leucine.[J]. Journal of biochemistry, 1996, 119 3: 572-576. DOI:10.1093/oxfordjournals.jbchem.a021280
[2] WILLIAM KA KEI WU. Macroautophagy and ERK phosphorylation counteract the antiproliferative effect of proteasome inhibitor in gastric cancer cells.[J]. Autophagy, 2010, 6 2: 228-238. DOI:10.4161/auto.6.2.11042
[3] A B MERIIN. Proteasome inhibitors activate stress kinases and induce Hsp72. Diverse effects on apoptosis.[J]. The Journal of Biological Chemistry, 1998, 273 11: 6373-6379. DOI:10.1074/jbc.273.11.6373
[4] M A FIEDLER  J M S  K Wernke Dollries. Inhibition of TNF-alpha-induced NF-kappaB activation and IL-8 release in A549 cells with the proteasome inhibitor MG-132.[J]. American Journal of Respiratory Cell and Molecular Biology, 1998, 19 2: 259-268. DOI:10.1165/ajrcmb.19.2.3149