product name MG-132
Description: MG-132 is a specific, potent, reversible, and cell-permeable inhibitor of proteasome with IC50 of 100 nM in a cell-free assay, and also inhibits calpain with IC50 of 1.2 μM. MG132 also inhibits NF-κB activation with an IC50 of 3 µM and prevents β-secretase cleavage. MG-132 induces MCPIP1 expression; induces C6 glioma cell apoptosis via oxidative stress; induces AIF nuclear translocation through down-regulation of ERK and Akt/mTOR pathway.
References: J Biochem. 1996;119(3):572-6; Am J Pathol. 2003;163(4):1663-75; BMC Musculoskelet Disord. 2011;12:185.
475.62
Formula
C26H41N3O5
CAS No.
133407-82-6
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 95 mg/mL (199.7 mM)
Water: <1 mg/mL
Ethanol: 95 mg/mL (199.7 mM)
Solubility (In vivo)
4% DMSO+30% PEG 300+20% propylene glycol+ddH2O: 2 mg/mL
Synonyms
other peoduct :
| In Vitro |
In vitro activity: MG-132 displays >1000 times more activity than ZLLal in inhibiting the ZLLL-MCA-degrading activity of 20S proteasome with IC50 of 100 nM versus 110 μM. MG-132 also inhibits calpain with IC50 of 1.2 μM. MG-132 induces neurite outgrowth in PC12 cells at an optimal concentration of 20 nM, displaying 500 times more potency than ZLLal. MG-132 (10 μM) potently inhibits TNF-α-induced NF-κB activation, interleukin-8 (IL-8) gene transcription, and IL-8 protein release in A549 cells by inhibition of proteasome-mediated IκBα degradation. MG-132 treatment potently induces p53-dependent apoptosis in KIM-2 cells by 26S proteasome inhibition. Unlike BzLLLCOCHO or PS-341, MG-132 treatment results in weak inhibition of the chymotrypsinlike (CT-L) and peptidylglutamyl peptide hydrolysing (PGPH) activities of the 26S proteasome, whereas multiple myeloma cells (U266 and OPM-2) are more sensitive to induction of apoptosis by MG-132 than BzLLLCOCHO. MG-132 (1 μM) sensitizes TRAIL-resistant prostate cancer cells by activating the AP-1 family members c-Fos and c-Jun, which, in turn, repress the antiapoptotic molecule c-FLIP(L). MG-132 significantly enhances the ability of inositol hexakisphosphate (IP6) to reduce cellular metabolic activity in both PC3 and DU145 androgen-independent prostate cancer (AIPCa) cell lines. Kinase Assay: The reaction mixture for the 20S proteasome inhibitory assay contains 0.1 M Tris-acetate, pH 7.0, 20S proteasome, MG-132, and 25 μM substrate dissolved in dimethyl sulfoxide in a final volume of 1 mL. After incuba tion at 37 °C for 15 minutes, the reaction is stopped by the addition of 0.1 mL of 10% SDS and 0.9 mL of 0.1M Tris acetate, pH 9.0. The fluorescence of the reaction products is measured. To determine the IC50 against 20S proteasome, various concentrations of MG-132 are included in the assay mixture. Cell Assay: Cells (KIM-2, HC11, and ES) are exposed to various concentrations of MG-132 for 24, and 48 hours. Supernatant and monolayer cells are harvested by centrifugation and fixed in 70% ethanol in PBS for staining with acridine orange. Equal volumes of cells and acridine orange (5 mg/mL in PBS) are mixed on a microscope slide and examined by fluorescence microscopy. For annexin V analysis, cells are harvested by centrifugation and stained with annexin V and propidium iodide. For cell cycle analysis, cells are rehydrated in PBS at room temperature for 10 minutes, followed by staining with propidium iodide (5 mg/mL). All samples are analyzed using a Coulter Epics XL flow cytometer. |
|---|---|
| In Vivo | Administration of MG-132 effectively rescues the expression levels and plasma membrane localization of dystrophin, β-dystroglycan, α-bdystroglycan, and α-sarcoglycan in skeletal muscle fibers from mdx mice, reduces muscle membrane damage, and ameliorates the histopathological signs of muscular dystrophy. MG-132 treatment significantly reduces immobilization-induced skeletal muscle atrophy in mice, by downregulating the muscle-specific ubiquitin ligases atrogin-1/MAFbx and MuRF-1 mRNA. |
| Animal model | Male mdx (C57BL/10ScSn DMD mdx) mice |
| Formulation & Dosage | Dissolved in DMSO, and diluted in PBS; 10 μg/kg; i.v. injection |
| References | J Biochem. 1996 Mar;119(3):572-6; Am J Pathol. 2003 Oct;163(4):1663-75; BMC Musculoskelet Disord. 2011 Aug 15;12:185. doi: 10.1186/1471-2474-12-185. |
