MG-132 化学構造
分子量: 475.62

品質と確認

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製品情報

  • Compare Proteasome Inhibitors
    Proteasome阻害剤を比較
  • 研究分野
  • Combination Therapy
    併用療法

製品の説明

生物活性

情報 MG-132は、100nMのIC50によるプロテアソームの強力な阻害剤です。
目標

Proteasome

IC50

100 nM [1]

In vitro試験 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試験 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]
臨床試験
特集

推薦された実験操作 (公開の文献だけ)

キナーゼアッセイ:

[1]

Measurement of inhibitory activities of MG-132 against 20S proteasome 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:

[3]

細胞系 KIM-2, HC11, and ES
濃度 Dissolved in DMSO, final concentrations ~25 μM
処理時間 24, and 48 hours
方法

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.

動物実験:

[7]

動物モデル Male mdx (C57BL/10ScSn DMD mdx) mice
製剤 Dissolved in DMSO, and diluted in PBS
投薬量 ~10 μg/kg/day
管理 Injection
Solubility 1% DMSO/30% polyethylene glycol/1% Tween 80, pH 4 6 mg/mL
* 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.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesBaboonDogMonkeyRabbitGuinea pigRatHamsterMouse
Weight (kg)121031.80.40.150.080.02
Body Surface Area (m2)0.60.50.240.150.050.0250.020.007
Km factor202012128653
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

参考

化学情報

Download MG-132 SDF
分子量 475.62
化学式

C26H41N3O5

CAS No. 133407-82-6
保管 2年-20℃
6月-80℃in DMSO
別名
溶解度 (25°C) * In vitro DMSO 95 mg/mL (199 mM)
<1 mg/mL (<1 mM)
エタノール 95 mg/mL (199 mM)
In vivo 1% DMSO/30% polyethylene glycol/1% Tween 80, pH 4 6 mg/mL
* <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.
化学名 benzyl (S)-4-methyl-1-((S)-4-methyl-1-((S)-4-methyl-1-oxopentan-2-ylamino)-1-oxopentan-2-ylamino)-1-oxopentan-2-ylcarbamate

研究分野

カスタマーレビュー (6)


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Source Nucleic Acids Res, 2014, 42(1):458-74. MG-132 purchased from Selleck
Method Western blot
Cell Lines HeLa cells
Concentrations 20 uM
Incubation Time 8 h
Results As RMND5A downregulation resulted in a rapid decrease of protein Exportin-5, this effect was partially abolished by the proteasome inhibitor MG132, indicating that RMND5A protect Exportin-5 protein against proteasome degradation.

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Rating
Source Nucleic Acids Res, 2014, 42(1):458-74. MG-132 purchased from Selleck
Method Immunocytochemistry
Cell Lines HeLa cells
Concentrations 20 uM
Incubation Time 8 h
Results It was surprised to observe that Exportin-5 retention in nucleus when its protein levels were downregulated by RMND5A siRNA or miR-138. The proteasome inhibitor MG132 could recover not only Exportin-5 protein levels but also its normal subcellular localization.

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Rating
Source EMBO Mol Med, 2013, 5, 397-412. MG-132 purchased from Selleck
Method Western Blot
Cell Lines MEF cells
Concentrations 30 uM
Incubation Time 6 h
Results Treatment of MEF with proteasome inhibitor MG132 resulted in similar increase of steady state levels of intracellular ATZ in both GFP- and TFEB- transfected Cells.

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Rating
Source Plant Physiol, 2012, 60(1):118-34. MG-132 purchased from Selleck
Method Immunoblot analysis
Cell Lines Arabidopsis thaliana
Concentrations 100 uM
Incubation Time 12 h
Results These rates of loss were markedly slower in the lrb1-1 lrb2-1 background. Importantly, phyB breakdown was also substantially attenuated upon exposing wild-type seedlings to the proteasome inhibitor MG132, thus implicating the 26S proteasome in particular. MG132 treatment also slightly stabilized phyB levels in lrb1-1 lrb2-1 seedlings, implying that other factors besides LRB1 and LRB2 might also direct phyB breakdown.

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Rating
Source FEBS Letters, 2012, 586, 3787–3792. MG-132 purchased from Selleck
Method Western Blot
Cell Lines Hela cells
Concentrations
Incubation Time 12 h
Results When GSK-3 (Ser9) degradation was blocked by proteasome inhibitor (MG132), the increased amount of phosphorylated GSK-3 (Ser9) in responding to NOK was more clearly observed in the HeLa-NOK-HA cells (Fig. C).

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Rating
Source Dr. Edison DUKE-NUS Graduate Medical School Singapore.. MG-132 purchased from Selleck
Method Western blot
Cell Lines NIH3T3 cells
Concentrations 25 μM
Incubation Time 1-4 h
Results By adding MG132, a proteasome inhibitor, the degradation of Per2 was dramatically decreased within 4 hours treatment.

製品表彰状 (18)

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