MG132,蛋白酶体抑制剂性质、用途与生产工艺
MG132,蛋白酶体抑制剂是一种有效，可逆，能渗透细细胞的20S蛋白酶抑制剂。它抑制蛋白酶体胰凝乳蛋白酶样肽酶活性的 IC50值为24.2 nM。MG-132以时间和剂量依赖性方式抑制问C6神经胶质瘤细胞增殖（24小时时的IC 50值为18.5μM）。 MG-132通过下调抗细胞凋亡答蛋白Bcl-2和XIAP，促内凋亡蛋白Bax和半胱天冬酶-3的上调以及切割的C端85kDa PARP的产生来诱导细胞凋亡。
MG-132是一种多肽醛，也是有效的，可逆的，可透过细胞的蛋白酶体抑制剂，IC50 值为 100 nM，有效地阻断了 26S 蛋白酶体复合物的蛋白水解活性。
MG132通过诱导细胞周期停滞以及引发细胞凋亡来抑制HeLa细胞的生长。 MG-132以时间和剂量依赖性方式抑制C6神经胶质瘤细胞增殖（24小时时的IC 50值为18.5μM）。 MG-132（18.5μM）在3小时时抑制蛋白酶体活性约70％。MG-132通过下调抗细胞凋亡蛋白Bcl-2和XIAP，促凋亡蛋白Bax和半胱天冬酶-3的上调以及切割的C端85kDa PARP的产生来诱导细胞凋亡。 MG-132还会使活性氧增加5倍以上。 孵育48小时后MG-132对HeLa，CaSki和C33A宫颈癌细胞存活率的IC50分别为2.1,3.2和5.2μM。
使用皮下注射检查MG-132对宫颈癌的体内抗肿瘤活性。 异种移植模型。 使用以下方案以1mg / kg注射MG-132：对于携带HeLa肿瘤的小鼠，第1,4,8,12,15,18,23和26天。 与对照相比，MG132的生长抑制率为49％。 MG-132（腹股沟，0.1 mg / kg /天）通过调节ERK1 / 2和JNK1信号通路减轻压力超负荷引起的心脏肥大并改善腹主动脉条带（AAB）大鼠的心脏功能。
MG-132 (Z-Leu-Leu-Leu-al) 是一种有效的，可逆的蛋白酶体 (proteasome) 抑制剂，IC50 为 100 nM。MG-132 有效阻断 26S 蛋白酶体复合物的蛋白水解活性。MG-132 是一种肽醛，是自噬 (autophagy) 激活剂。MG-132 还诱导凋亡 (apoptosis)。
IC50: 100 nM (Proteasome), 1.2 μM (Calpain)
MG-132 (Z-Leu-Leu-Leu-al) initiates neurite outgrowth in PC12 cells at a low concentration (30 nM) and is a very strong inhibitor of 20S proteasome.
MG-132 (10 μM; 1 hour) reverses the effects of TNF- α on I κ B degradation and NF-κ B activation in A549 cells.
MG-132 (0.75-5 μM; 24 hours) potently induces p53-dependent apoptosis in KIM-2 cells by 26S proteasome inhibition.
MG-132 (10-40 μM; 24 hours) significantly reduces the viability of C6 glioma cells in both time- and concentration-dependent manners and shows the IC
50
of 18.5 μM at 24 hours.
MG-132 (18.5 μM; 24 hours) induces down-regulation of anti-apoptotic proteins Bcl-2 and XIAP and up-regulates expression of pro-apoptotic protein Bax and caspase-3.
Cell Viability Assay
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Cell Line:
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C6 glioma cells
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Concentration:
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10, 20, 30, 40 μM
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Incubation Time:
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24 hours
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Result:
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Significantly reduced the viability of C6 glioma cells beginning at 6 h in both time- and concentration-dependent manners and showed the IC
50
of 18.5 μM at 24 hours.
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Western Blot Analysis
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Cell Line:
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A549 cells
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Concentration:
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10 μM
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Incubation Time:
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1 hour
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Result:
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Reversed the effects of TNF-α on IκB degradation and resulted in a reversal of TNF-α-induced NF-κB activation.
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MG132 (10 mg/kg; i.p.; daily for 25 days starting 5 days after EC9706 cells injection) significantly inhibits tumor growth of the EC9706 xenograft without causing toxicity to mice.
MG-132 (1 mg/kg; i.v.; twice a week for 4 weeks) shows potent tumor inhibitory effect against mice bearing HeLa tumors.
MG-132 (1-10 μg/kg/24 hours; subcutaneously implanted osmotic pumps; for 8 days) greatly increases the expression levels of β-dystroglycan, α-dystroglycan, α-sarcoglycan, and dystrophin in skeletal muscle lysates in mice (six-month-old male C57BL/10ScSn DMD mdx mice).
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Animal Model:
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5- to 6-weeks old female athymic nude mice (EC9706 xenograft)
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Dosage:
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10 mg/kg
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Administration:
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I.p.; daily for 25 days starting 5 days after EC9706 cells injection
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Result:
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Significantly inhibited tumor growth of the EC9706 xenograft without causing toxicity to the mice.
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Animal Model:
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Five-week-old female C.B-17/lcr-scid/scidJcl mice (bearing HeLa cells)
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Dosage:
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1 mg/kg
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Administration:
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Intravenous injection; twice a week for 4 weeks
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Result:
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The growth inhibition rates in HeLa tumors was 49% compared to the control.
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MG132,蛋白酶体抑制剂
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