MG-132 (Synonyms: Z-Leu-Leu-Leu-al; MG132)

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)。

体外研究(In Vitro)

MG-132（Z-Leu-Leu-Leu-al）在低浓度（30nM）下启动PC12细胞中的神经轴突生长，是20S蛋白酶体的非常强的抑制剂[3]。

MG-132（10μM；1小时）逆转了TNF-α对A549细胞中IκB降解和NF-κB激活的影响[4]。

MG-132（0.75-5μM；24小时）通过26S蛋白酶体抑制，潜在地诱导KIM-2细胞中的p53依赖性凋亡[5]。

MG-132（10-40μ。

MG-132（18.5μM；24小时）诱导抗凋亡蛋白Bcl-2和XIAP的下调，并上调促凋亡蛋白Bax和caspase-3的表达

体内研究(In Vivo)

MG132（10mg/kg；腹腔注射；从EC9706细胞注射后5天开始每天持续25天）显著抑制EC9706异种移植物的肿瘤生长，而不会对小鼠产生毒性[7]。

MG-132（1mg/kg；静脉注射；每周两次，持续4周）对荷HeLa肿瘤的小鼠显示出强大的肿瘤抑制作用。

分子量：475.62

Formula：C₂₆H₄₁N₃O₅

CAS 号：133407-82-6

运输条件：Room temperature in continental US; may vary elsewhere.

储存方式：

参考文献：

[1]. Harhouri K, et al. MG132-induced progerin clearance is mediated by autophagy activation and splicing regulation. EMBO Mol Med. 2017 Sep;9(9):1294-1313.

[2]. Fan WH, et al. Proteasome inhibitor MG-132 induces C6 glioma cell apoptosis via oxidative stress. Acta Pharmacol Sin. 2011 May;32(5):619-25.

[3]. Tsubuki S, et al. Differential inhibition of calpain and proteasome activities by peptidyl aldehydes of di-leucine and tri-leucine. J Biochem. 1996 Mar;119(3):572-6.

[4]. Fiedler MA, et al. Inhibition of TNF-alpha-induced NF-kappaB activation and IL-8 release in A549 cells with the proteasome inhibitor MG-132. Am J Respir Cell Mol Biol. 1998 Aug;19(2):259-68.

[5]. MacLaren AP, et al. p53-dependent apoptosis induced by proteasome inhibition in mammary epithelial cells. Cell Death Differ. 2001 Mar;8(3):210-8.

[6]. Han YH, et al. The effect of MG132, a proteasome inhibitor on HeLa cells in relation to cell growth, reactive oxygen species and GSH. oncol Rep. 2009 Jul;22(1):215-21.

[7]. Dang L, et al. Proteasome inhibitor MG132 inhibits the proliferation and promotes the cisplatin-inducedapoptosis of human esophageal squamous cell carcinoma cells. Int J Mol Med. 2014 May;33(5):1083-8.

[8]. Matsumoto Y, et al. Enhanced efficacy against cervical carcinomas through polymeric micelles physically incorporating theproteasome inhibitor MG132. Cancer Sci. 2016 Jun;107(6):773-81.

[9]. Bonuccelli G, et al. Proteasome inhibitor (MG-132) treatment of mdx mice rescues the expression and membrane localization of dystrophin and dystrophin-associated proteins. Am J Pathol. 2003 Oct;163(4):1663-75.