MG132,蛋白酶体抑制剂

中文名称:

MG132,蛋白酶体抑制剂

中文同义词:

MG132,蛋白酶体抑制剂;N-[(苄氧基)羰基]-L-亮氨酰-N-[(1S)-1-甲酰基-3-甲基丁基]-L-亮氨酰胺;蛋白酶体抑制剂2;MG-132肽;((S)-4-甲基-1-(((S)-4-甲基-1-(((S)-4-甲基-1-氧代戊烷-2-基)氨基)-1-氧代戊烷-2-基)氨基)-1-氧代戊烷-2-基)氨基甲酸苄酯

英文名称:

MG-132

英文同义词:

PROTEASOME INHIBITOR MG-132;N-[(PHENYLMETHOXY)CARBONYL]-L-LEUCYL-N-[(1S)-1-FORMYL-3-METHYLBUTYL]-L-LEUCINAMIDE;N-CBZ-LEU-LEU-LEUCINAL;MG-132;Z-LLL-CHO;Z-LL-CHO;Z-LEU-LEU-LEU-CHO;Z-LEU-LEU-LEU-H

CAS号:

133407-82-6

分子式:

C26H41N3O5

分子量:

475.62

EINECS号:

相关类别:

多肽;抑制剂;信号转导通路激酶抑制剂;小分子抑制剂，天然产物;小分子抑制剂;蛋白酶;生物化工;API;Aldehydes;and Substrates;Application Index;Bioactive Small Molecules;Biochemicals and Reagents;Building Blocks;C13-C60;Calpain and Lysosomal Proteases;Calpain and Proteasome Inhibitors;Carbonyl Compounds;Cell Biology;peptides;inhibitor;Cytokine signaling;Apoptosis Inducers;Cell Signaling and Neuroscience;Cell Signaling Enzymes;Chemical Synthesis;Enzymes;Inhibitors;Intracellular Protein Degradation;Nitric Oxide and Cell Stress;Organic Building Blocks;Proteasome;Proteasomes;Z;ProteasomeInhibitors

Mol文件:

133407-82-6.mol

熔点 

80-84℃ (DEC.)

比旋光度 

-61～-67°

沸点 

682.0±55.0 °C(Predicted)

密度 

1.073

闪点 

366℃

储存条件 

-20°C

溶解度 

methanol: 1 mg/mL

酸度系数(pKa)

11.14±0.46(Predicted)

形态

solid film

颜色

White

水溶解性 

Soluble in ethanol, chloroform, methanol, water.

InChIKey

TZYWCYJVHRLUCT-VABKMULXSA-N

概述

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。

作用

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。

体外活性

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。

体内活性

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。

生物活性

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)。

靶点

IC50: 100 nM (Proteasome), 1.2 μM (Calpain)

体外研究

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 Cell Line: C6 glioma cells Concentration: 10, 20, 30, 40 μM Incubation Time: 24 hours Result: 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. Western Blot Analysis Cell Line: A549 cells Concentration: 10 μM Incubation Time: 1 hour Result: Reversed the effects of TNF-α on IκB degradation and resulted in a reversal of TNF-α-induced NF-κB activation.

Cell Line:

C6 glioma cells

Concentration:

10, 20, 30, 40 μM

Incubation Time:

24 hours

Result:

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.

Cell Line:

A549 cells

Concentration:

10 μM

Incubation Time:

1 hour

Result:

Reversed the effects of TNF-α on IκB degradation and resulted in a reversal of TNF-α-induced NF-κB activation.

体内研究

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). Animal Model: 5- to 6-weeks old female athymic nude mice (EC9706 xenograft) Dosage: 10 mg/kg Administration: I.p.; daily for 25 days starting 5 days after EC9706 cells injection Result: Significantly inhibited tumor growth of the EC9706 xenograft without causing toxicity to the mice. Animal Model: Five-week-old female C.B-17/lcr-scid/scidJcl mice (bearing HeLa cells) Dosage: 1 mg/kg Administration: Intravenous injection; twice a week for 4 weeks Result: The growth inhibition rates in HeLa tumors was 49% compared to the control.

Animal Model:

5- to 6-weeks old female athymic nude mice (EC9706 xenograft)

Dosage:

10 mg/kg

Administration:

I.p.; daily for 25 days starting 5 days after EC9706 cells injection

Result:

Significantly inhibited tumor growth of the EC9706 xenograft without causing toxicity to the mice.

Animal Model:

Five-week-old female C.B-17/lcr-scid/scidJcl mice (bearing HeLa cells)

Dosage:

1 mg/kg

Administration:

Intravenous injection; twice a week for 4 weeks

Result:

The growth inhibition rates in HeLa tumors was 49% compared to the control.

危险类别码 

36/37/38

安全说明 

24/25

WGK Germany 

3

海关编码 

29242990