MG-115 |
| رقم الكتالوجGC10178 |
MG-115 is a potent inhibitor with Kis of 21 nM and 35 nM for 20S and 26S proteasome, respectively.
Products are for research use only. Not for human use. We do not sell to patients.
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.
| Kinase experiment [1]: | |
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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]: | |
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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. |
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| Cas No. | 133407-86-0 | SDF | |
| Chemical Name | 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 | ||
| Formula | C25H39N3O5 | M.Wt | 461.59 |
| الذوبان | 25mg/mL in DMSO, 25mg/mL in DMF, 30mg/mL in Ethanol | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
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 |
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- Purity: >98.00%
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