MG-115
(Synonyms: MG115,蛋白酶体抑制剂,Carbobenzoxy-L-leucyl-L-leucyl-L-norvalinal, Z-LL-Nva-CHO, Proteasome Inhibitor XII,MG115) 目录号 : GC10178
MG-115 是一种有效的抑制剂，对 20S 和 26S 蛋白酶体的 Kis 分别为 21 nM 和 35 nM 。
Cas No.:133407-86-0
Sample solution is provided at 25 µL, 10mM.
MG-115 is a potent inhibitor with Kis of 21 nM and 35 nM for 20S and 26S proteasome, respectively [1].
MG-115 (50 μM, 2 h) increased the expression of the insulin receptor and its mature beta subunit by a factor of 3 and 4.2, respectively in Leu1193 and Asp1179 COS-7 mutant cell lines[2].Treated Rat-1 and PC12 cells with MG-115(30 μM, 4 h) can induced apoptosis of both cell types[3]. Iisolated rat islets were cultured and pre-treated with proteasome inhibitors and subsequently exposed for 48 h to 25 U/ml human IL-1beta. Pre-treatment with 10 uM of the proteasome inhibitor MG-115 counteracted the suppressive effects[4]. HCC cells SK-Hep1, HLE and HepG2 were treated with the proteasome inhibitors MG-115. MG-115 induce apoptosis in the three cell types tested in a dose-dependent manner. MG-115 downregulated expression of XIAP in SK-Hep1, and survivin in SK-Hep1 and HepG2[5]. MG-115 decreased within 120 min the aldosterone and corticosterone secretion from freshly dispersed zona glomerulosa and zona fasciculata-reticularis (ZF/R) cells. After a 24-h incubation MG-115 alone lowered corticosterone production and enhanced proliferation rate of cultured ZF/R cells[6]. The proteasome inhibitor MG-115 can inhibit ATF6, which is the direct target of the proteasome-ubiquitin pathway[7]. MG-115 was diminished by adding at a time corresponding to the half time required for germinal vesicle breakdown. Potent inhibition of germinal vesicle breakdown was also observed by microinjection of anti-proteasome-a-subunit antibodies[8]. MG-115 induced a decrease in Bid, Bcl-2, and survivin protein levels, an increase in Bax, loss of the mitochondrial transmembrane potential, cytochrome c release, activation of caspases (-8, -9 and -3), and an increase in the tumor suppressor p53 levels in PC3[9].
References:
[1]. Rock KL, Gramm C, et,al. Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules. Cell. 1994 Sep 9;78(5):761-71. doi: 10.1016/s0092-8674(94)90462-6. PMID: 8087844.
[2]. Imamura T, Haruta T, et,al. Involvement of heat shock protein 90 in the degradation of mutant insulin receptors by the proteasome. J Biol Chem. 1998 May 1;273(18):11183-8. doi: 10.1074/jbc.273.18.11183. PMID: 9556607
[3]. Lopes UG, Erhardt P, et,al. p53-dependent induction of apoptosis by proteasome inhibitors. J Biol Chem. 1997 May 16;272(20):12893-6. doi: 10.1074/jbc.272.20.12893. PMID: 9148891.
[4]. Sternesj? J, Karlsen AE, et,al.Involvement of the proteasome in IL-1beta induced suppression of islets of Langerhans in the rat. Ups J Med Sci. 2003;108(1):37-50. doi: 10.3109/2000-1967-122. PMID: 12903836.
[5]. Inoue T, Shiraki K, et,al. Proteasome inhibition sensitizes hepatocellular carcinoma cells to TRAIL by suppressing caspase inhibitors and AKT pathway. Anticancer Drugs. 2006 Mar;17(3):261-8. doi: 10.1097/00001813-200603000-00004. PMID: 16520654.
[6]. Ziolkowska A, Tortorella C, et,al.Accumulation of steroidogenic acute regulatory protein mRNA, and decrease in the secretory and proliferative activity of rat adrenocortical cells in the presence of proteasome inhibitors. Int J Mol Med. 2006 May;17(5):865-8. PMID: 16596272.
[7]. Hong M, Li M, et,al. Endoplasmic reticulum stress triggers an acute proteasome-dependent degradation of ATF6. J Cell Biochem. 2004 Jul 1;92(4):723-32. doi: 10.1002/jcb.20118. PMID: 15211570.
[8].Takagi Sawada M,et,al. The proteasome is an essential mediator of the activation of pre-MPF during starfish oocyte maturation. Biochem Biophys Res Commun. 1997 Jul 9;236(1):40-3. doi: 10.1006/bbrc.1997.6900. PMID: 9223422.
[9].Nam YJ, Lee DH, et,al. 3,4,5-tricaffeoylquinic acid attenuates proteasome inhibition-mediated programmed cell death in differentiated PC12 cells. Neurochem Res. 2014 Aug;39(8):1416-25. doi: 10.1007/s11064-014-1327-x. Epub 2014 May 14. PMID: 24825618.
MG-115 是一种有效的抑制剂，对 20S 和 26S 蛋白酶体的 Kis 分别为 21 nM 和 35 nM [1]。
MG-115（50 μM，2 小时）在 Leu1193 和 Asp1179 COS-7 突变细胞系中分别将胰岛素受体及其成熟 β 亚基的表达提高 3 倍和 4.2 倍[2] .MG-115(30 μM, 4 h)处理Rat-1和PC12细胞可诱导两种细胞的凋亡[3]。培养分离的大鼠胰岛并用蛋白酶体抑制剂预处理，随后暴露 48 小时至 25 U/ml 人 IL-1beta。用 10 uM 蛋白酶体抑制剂 MG-115 进行预处理可抵消抑制作用[4]。用蛋白酶体抑制剂 MG-115 处理 HCC 细胞 SK-Hep1、HLE 和 HepG2。 MG-115 以剂量依赖的方式在三种细胞类型中诱导细胞凋亡。 MG-115 下调 SK-Hep1 中 XIAP 的表达，下调 SK-Hep1 和 HepG2 中 survivin 的表达[5]。 MG-115 在 120 分钟内减少了新鲜分散的球状带和束状带-网状 (ZF/R) 细胞的醛固酮和皮质酮分泌。孵育 24 小时后，单独使用 MG-115 可降低皮质酮的产生并提高培养的 ZF/R 细胞的增殖率[6]。蛋白酶体抑制剂 MG-115 可以抑制 ATF6，ATF6 是蛋白酶体-泛素通路的直接靶点[7]。 MG-115 通过在与生发泡破裂所需的一半时间相对应的时间添加而减少。通过显微注射抗蛋白酶体-a-亚基抗体[8]，也观察到对生发泡破裂的有效抑制。 MG-115 诱导 Bid、Bcl-2 和存活蛋白水平降低，Bax 增加，线粒体跨膜电位丧失，细胞色素 c 释放，半胱天冬酶（-8、-9 和 -3）激活，以及PC3[9] 中肿瘤抑制因子 p53 水平的增加。
| Kinase experiment [1]: | |
|
Preparation Method |
Proteasome fractions were prepared from rabbit psoas muscle homogenates by differential centrifugation and were resolved into 26S and 20S particles by precipitation with ammonium sulfate (0%-38% and 40%-80%, respectively) followed by chromatography sequentially on a Mono Q and a Superose 6 column. Peptide-AMC substrates and inhibitor(including MG-115) (1-10 μl) in DMSO were added to 2 ml of assay buffer that for the 20S proteasome contained 20 mM Tris-HCI, 0.5 mM EDTA, and 0.035% SDS (pH 8.0); for the 26S proteasome, contained 20 mM Tris-HCI, 1 mM ATP, and 2 mM MgCls (pH 8.0); for cathepsin B, contained 100 mM NaOAc, 5 mM EDTA, and 2 mM DTT; and for calpain, contained 20 mM Tris-HCI, 1 mM CaCl2, and 2 mM DTT (pH 8.0). After equilibration at 37℃ (proteasomes and cathepsin B) or 20℃ (calpain), enzyme (1-5 μl) was added, and reaction progress was monitored by the increase in fluorescence emission at 440 nm (lar, 380 nm). |
|
Applications |
MG-115 is a more potent inhibitor with Kis of 21 nM and 35 nM for 20S and 26S proteasome, respectively. |
| Cell experiment [2]: | |
|
Cell lines |
Rat-1 and PC12 cells |
|
Preparation Method |
Actively proliferating Rat-1 fibroblasts and PC12 pheochromocytoma cells were treated with PSI and MG-115. After 4 h of treatment, apoptosis was assayed by DNA fragmentation. |
|
Reaction Conditions |
30 μM MG-115 for 4 h |
|
Applications |
Both Rat-1 and PC12 cells underwent apoptosis following treatment with MG-115. |
|
References: [1]. Rock KL, Gramm C, et,al. Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules. Cell. 1994 Sep 9;78(5):761-71. doi: 10.1016/s0092-8674(94)90462-6. PMID: 8087844. [2]. Lopes UG, Erhardt P, et,al. p53-dependent induction of apoptosis by proteasome inhibitors. J Biol Chem. 1997 May 16;272(20):12893-6. doi: 10.1074/jbc.272.20.12893. PMID: 9148891. |
|
| Cas No. | 133407-86-0 | SDF | |
| 别名 | MG115,蛋白酶体抑制剂,Carbobenzoxy-L-leucyl-L-leucyl-L-norvalinal, Z-LL-Nva-CHO, Proteasome Inhibitor XII,MG115 | ||
| 化学名 | benzyl N-[(2S)-4-methyl-1-[[(2S)-4-methyl-1-oxo-1-[[(2S)-1-oxopentan-2-yl]amino]pentan-2-yl]amino]-1-oxopentan-2-yl]carbamate | ||
| Canonical SMILES | CCCC(C=O)NC(=O)C(CC(C)C)NC(=O)C(CC(C)C)NC(=O)OCC1=CC=CC=C1 | ||
| 分子式 | C25H39N3O5 | 分子量 | 461.59 |
| 溶解度 | 25mg/mL in DMSO, 25mg/mL in DMF, 30mg/mL in Ethanol | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.1664 mL | 10.8321 mL | 21.6642 mL |
| 5 mM | 0.4333 mL | 2.1664 mL | 4.3328 mL |
| 10 mM | 0.2166 mL | 1.0832 mL | 2.1664 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet