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Synonyms | (S,R,S)-(-)-MG-132, Z-Leu-D-Leu-Leu-al | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C26H41N3O5 |
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分子量 | 475.62 | CAS No. | 1211877-36-9 | |
Solubility (25°C)* | 体外 | DMSO | 95 mg/mL (199.73 mM) | |
Ethanol | 95 mg/mL (199.73 mM) | |||
Water | Insoluble | |||
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
製品説明 | MG132 ((S,R,S)-(-)-MG132, Z-Leu-D-Leu-Leu-al) は、強力なプロテアソーム(ChTL、TL、PGPH) 阻害剤です。 MG132 はカルパイン (calpain) も阻害します (IC50 = 1.2 μM)。 |
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in vitro | 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. [1] 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. [2] MG-132 treatment potently induces p53-dependent apoptosis in KIM-2 cells by 26S proteasome inhibition. [3] 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. [4] 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). [5] 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. [6] |
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. [7] 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. [8] |
キナーゼアッセイ | Measurement of inhibitory activities of MG-132 against 20S proteasome | |
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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. | ||
細胞アッセイ | 細胞株 | KIM-2, HC11, and ES |
濃度 | Dissolved in DMSO, final concentrations ~25 μM | |
反応時間 | 24 and 48 hours | |
実験の流れ | Cells 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. |
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動物実験 | 動物モデル | Male mdx (C57BL/10ScSn DMD mdx) mice |
投薬量 | ~10 μg/kg/day | |
投与方法 | Injection |
Data from [Data independently produced by Nat Cell Biol, 2015, 17(1), 95-103]
Data from [Data independently produced by Cell Rep, 2015, 11(9), 1458-73]
Data from [Data independently produced by Toxicol Appl Pharmacol, 2015, 286(2), 135-41]
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Proteostatic reactivation of the developmental transcription factor TBX3 drives BRAF/MAPK-mediated tumorigenesis [ Nat Commun, 2024, 15(1):4108] | PubMed: 38750011 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
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