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

MG-132 (Z-Leu-Leu-Leu-al) 是一種有效的，可逆的蛋白酶體 (proteasome) 抑制劑，IC₅₀ 為 100 nM。MG-132 有效阻斷 26S 蛋白酶體復(fù)合物的蛋白水解活性。MG-132 是一種肽醛，是自噬 (autophagy) 激活劑。MG-132 還誘導(dǎo)凋亡 (apoptosis)。

體外研究(In Vitro)

MG-132（Z-Leu-Leu-Leu-al）在低濃度（30nM）下啟動(dòng)PC12細(xì)胞中的神經(jīng)軸突生長(zhǎng)，是20S蛋白酶體的非常強(qiáng)的抑制劑[3]。

MG-132（10μM；1小時(shí)）逆轉(zhuǎn)了TNF-α對(duì)A549細(xì)胞中IκB降解和NF-κB激活的影響[4]。

MG-132（0.75-5μM；24小時(shí)）通過(guò)26S蛋白酶體抑制，潛在地誘導(dǎo)KIM-2細(xì)胞中的p53依賴(lài)性凋亡[5]。

MG-132（10-40μ。

MG-132（18.5μM；24小時(shí)）誘導(dǎo)抗凋亡蛋白Bcl-2和XIAP的下調(diào)，并上調(diào)促凋亡蛋白Bax和caspase-3的表達(dá)

體內(nèi)研究(In Vivo)

MG132（10mg/kg；腹腔注射；從EC9706細(xì)胞注射后5天開(kāi)始每天持續(xù)25天）顯著抑制EC9706異種移植物的腫瘤生長(zhǎng)，而不會(huì)對(duì)小鼠產(chǎn)生毒性[7]。

MG-132（1mg/kg；靜脈注射；每周兩次，持續(xù)4周）對(duì)荷HeLa腫瘤的小鼠顯示出強(qiáng)大的腫瘤抑制作用。

分子量：475.62

Formula：C₂₆H₄₁N₃O₅

CAS 號(hào)：133407-82-6

運(yùn)輸條件：Room temperature in continental US; may vary elsewhere.

儲(chǔ)存方式：

參考文獻(xiàn)：

[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.