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    InvivoChem Cat #: V0685
    CAS #: 133407-82-6Purity ≥98%

    Description: MG-132, a peptide aldehyde, is a novel, 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. 

    References: J Biochem. 1996;119(3):572-6; Am J Pathol. 2003;163(4):1663-75; BMC Musculoskelet Disord. 2011;12:185.

    Related CAS: 133407-82-6 (MG-132); 1211877-36-9 (R-isomer)

    Publications Citing Use of InvivoChem MG-132: Eur J Med Chem. 2020 May 5;199:112377

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    Molecular Weight (MW)475.62
    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
    SynonymsMG-132; MG132; MG 132; benzyl ((S)-4-methyl-1-(((S)-4-methyl-1-(((S)-4-methyl-1-oxopentan-2-yl)amino)-1-oxopentan-2-yl)amino)-1-oxopentan-2-yl)carbamate 


    InChi Code: InChI=1S/C26H41N3O5/c1-17(2)12-21(15-30)27-24(31)22(13-18(3)4)28-25(32)23(14-19(5)6)29-26(33)34-16-20-10-8-7-9-11-20/h7-11,15,17-19,21-23H,12-14,16H2,1-6H3,(H,27,31)(H,28,32)(H,29,33)/t21-,22-,23-/m0/s1

    SMILES Code: O=C(OCC1=CC=CC=C1)N[[email protected]@H](CC(C)C)C(N[[email protected]@H](CC(C)C)C(N[[email protected]@H](CC(C)C)C=O)=O)=O

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    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 VivoAdministration 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 modelMale mdx (C57BL/10ScSn DMD mdx) mice
    Formulation & DosageDissolved in DMSO, and diluted in PBS; 10 μg/kg; i.v. injection

    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.

    These protocols are for reference only. InvivoChem does not independently validate these methods.

    Localized treatment of mdx mice with MG-132: Immunohistochemistry. Am J Pathol. 2003 Oct;163(4):1663-75.
    EBD staining of the diaphragm in mdx mice after systemic treatment with MG-132. Am J Pathol. 2003 Oct;163(4):1663-75.
    Systemic treatment of mdx mice with proteasomal inhibitor: immunohistochemistry. Am J Pathol. 2003 Oct;163(4):1663-75.




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