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Purity: ≥98%
MG-132, a peptide aldehyde, is a novel, specific, potent, reversible, and cell-permeable proteasome inhibitor with an IC50 of 100 nM in a cell-free assay. It also has an IC50 of 1.2 μM for calpain inhibition.
| Targets |
Proteasome (IC50 = 100 nM); Calpain (IC50 = 1.2 μM)
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|---|---|
| ln Vitro |
MG-132 exhibits over 1000 times greater activity than ZLLal in suppressing the 20S proteasome's ZLLL-MCA-degrading activity, with an IC50 of 100 nM as opposed to 110 μM. With an IC50 of 1.2 μM, MG-132 also inhibits calpain. At an ideal concentration of 20 nM, MG-132 exhibits 500 times greater potency than ZLLal in inducing neurite outgrowth in PC12 cells.[1] MG-132 (10 μM) inhibits the proteasome-mediated degradation of IκBα in A549 cells, thereby potently inhibiting TNF-α-induced NF-κB activation, IL-8 gene transcription, and IL-8 protein release.[2] MG-132 treatment strongly inhibits 26S proteasome, thereby inducing p53-dependent apoptosis in KIM-2 cells.[3] Multiple myeloma cells (U266 and OPM-2) are more susceptible to MG-132-induced apoptosis than BzLLLCOCHO, but MG-132 treatment results in weak inhibition of the chymotrypsinlike (CT-L) and peptidylglutamyl peptide hydrolysing (PGPH) activities of the 26S proteasome, in contrast to BzLLLCOCHO or PS-341.[4] By activating AP-1 family members c-Fos and c-Jun, which in turn repress the antiapoptotic molecule c-FLIP(L), MG-132 (1 μM) sensitizes TRAIL-resistant prostate cancer cells.[5] In the PC3 and DU145 androgen-independent prostate cancer (AIPCa) cell lines, MG-132 dramatically increases inositol hexakisphosphate's (IP6) capacity to lower cellular metabolic activity.[6]
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| ln Vivo |
In skeletal muscle fibers from mdx mice, MG-132 administration efficiently restores the expression levels and plasma membrane localization of dystrophin, β-dystroglycan, α-bdystroglycan, and α-sarcoglycan, minimizes damage to muscle membranes, and improves the histopathological symptoms of muscular dystrophy.[8] By downregulating the muscle-specific ubiquitin ligases atrogin-1/MAFbx and MuRF-1 mRNA, MG-132 treatment dramatically reduces immobilization-induced skeletal muscle atrophy in mice.[8]
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| Enzyme Assay |
MG-132, 20S proteasome, pH 7.0, 0.1 M Tris-acetate, and 25 μM substrate dissolved in dimethyl sulfoxide in a final volume of 1 mL make up the reaction mixture for the 20S proteasome inhibitory assay. 0.1 mL of 10% SDS and 0.9 mL of 0.1M Tris acetate, pH 9.0, are added to stop the reaction after it has been incubated at 37 °C for 15 minutes. The reaction products' fluorescence is measured. Different concentrations of MG-132 are added to the assay mixture in order to calculate the IC50 against 20S proteasome.
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| Cell Assay |
MG-132 is added to cells at different concentrations for 24, and 48 hours. Centrifugation is used to collect the supernatant and monolayer cells, which are then preserved in 70% ethanol in PBS before being stained with acridine orange. Acridine orange (5 mg/mL in PBS) and equal volumes of cells are combined on a microscope slide, and fluorescence microscopy is used to examine the mixture. Cells are collected by centrifugation and stained with propidium iodide and annexin V for annexin V analysis. Propidium iodide (5 mg/mL) staining is done after rehydrating cells in PBS at room temperature for ten minutes in order to analyze the cell cycle. Utilizing a Coulter Epics XL flow cytometer, every sample is examined.
Cell Viability Assay[1] Cell Types: C6 glioma cells Tested Concentrations: 10, 20, 30, 40 μM Incubation Duration: 24 hrs (hours) Experimental Results: Dramatically decreased the viability of C6 glioma cells beginning at 6 h in both time- and concentration-dependent manners and showed the IC50 of 18.5 μM at 24 hours. Cell Viability Assay[1] Cell Types: A549 cells Tested Concentrations: 10 μM Incubation Duration: 1 hrs (hours) Experimental Results: Reversed the effects of TNF-α on IκB degradation and resulted in a reversal of TNF-α-induced NF-κB activation. |
| Animal Protocol |
Animal/Disease Models: Female athymic nude mice bearing EC9706 xenograft (5- to 6-weeks old) [10]
Doses: 10 mg/kg Route of Administration: i.p.; daily for 25 days starting 5 days after inoculation of EC9706 tumors Experimental Results: Dramatically suppressed tumor growth of the EC9706 xenograft without apparrent toxicity to mice. Animal/Disease Models: Female C.B-17/lcr-scid/scidJcl mice bearing HeLa tumors (5- to 6-weeks old) [10] Doses: 10 mg/kg Route of Administration: Intravenous/i.v. injection; twice a week for 4 weeks Experimental Results: The growth inhibition rates in HeLa tumors was 49% compared to the control. Dramatically suppressed tumor growth of HeLa tumors with a TGI of 49%. Male mdx (C57BL/10ScSn DMD mdx) mice ~10 μg/kg/day Injection |
| References |
[1]. J Biochem. 1996 Mar;119(3):572-6. [2]. Am J Respir Cell Mol Biol. 1998 Aug;19(2):259-68. [3]. Cell Death Differ. 2001 Mar;8(3):210-8. [4]. Cancer Res. 2006 Jun 15;66(12):6379-86. [5]. J Med ChemCancer Res. 2007 Mar 1;67(5):2247-55. [6]. Br J Cancer. 2008 Nov 18;99(10):1613-22. [7]. Am J Pathol. 2003 Oct;163(4):1663-75. [8]. BMC Musculoskelet Disord. 2011 Aug 15:12:185. |
| Additional Infomation |
N-benzyloxycarbonyl-L-leucyl-L-leucyl-L-leucinal is a tripeptide that is L-leucyl-L-leucyl-L-leucine in which the C-terminal carboxy group has been reduced to the corresponding aldehyde and the N-terminal amino group is protected as its benzyloxycarbonyl derivative. It has a role as a proteasome inhibitor. It is a tripeptide, an amino aldehyde and a carbamate ester.
Z-Leu-leu-leu-al has been reported in Tricholoma pardinum, Glycyrrhiza glabra, and Glycyrrhiza inflata with data available. |
| Molecular Formula |
C26H41N3O5
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|---|---|
| Molecular Weight |
475.62
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| Exact Mass |
475.304
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| Elemental Analysis |
C, 65.66; H, 8.69; N, 8.83; O, 16.82
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| CAS # |
133407-82-6
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| Related CAS # |
(R)-MG-132;1211877-36-9;MG-132 (negative control)
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| PubChem CID |
462382
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| Sequence |
Z-Leu-Leu-Leu-al
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| Appearance |
White to yellow solid powder
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| Density |
1.1±0.1 g/cm3
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| Boiling Point |
682.0±55.0 °C at 760 mmHg
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| Melting Point |
80-84℃ (DEC.)
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| Flash Point |
366.3±31.5 °C
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| Vapour Pressure |
0.0±2.1 mmHg at 25°C
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| Index of Refraction |
1.506
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| LogP |
5.75
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
15
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| Heavy Atom Count |
34
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| Complexity |
644
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| Defined Atom Stereocenter Count |
3
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| SMILES |
O=C([C@]([H])(C([H])([H])C([H])(C([H])([H])[H])C([H])([H])[H])N([H])C([C@]([H])(C([H])([H])C([H])(C([H])([H])[H])C([H])([H])[H])N([H])C(=O)OC([H])([H])C1C([H])=C([H])C([H])=C([H])C=1[H])=O)N([H])[C@]([H])(C([H])=O)C([H])([H])C([H])(C([H])([H])[H])C([H])([H])[H]
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| InChi Key |
TZYWCYJVHRLUCT-VABKMULXSA-N
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| InChi Code |
InChI=1S/C26H41N3O5/c1-17(2)12-21(15-30)27-24(31)22(13-18(3)4)28-25(32)23(14-19(5)6)29-26(33)34-16-20-10-8-7-9-11-20/h7-11,15,17-19,21-23H,12-14,16H2,1-6H3,(H,27,31)(H,28,32)(H,29,33)/t21-,22-,23-/m0/s1
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| Chemical Name |
benzyl N-[(2S)-4-methyl-1-[[(2S)-4-methyl-1-[[(2S)-4-methyl-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]carbamate
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| Synonyms |
MG-132; MG 132; MG132; MGI132; MGI 132; Z-Leu-leu-leu-al; Zlllal; Z-Leu-leu-leucinal; Z-LLL-CHO; MGI-132
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.67 mg/mL (3.51 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 1.67 mg/mL (3.51 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 1.67 mg/mL (3.51 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 4% DMSO+30% PEG 300+20% propylene glycol+ddH2O: 2 mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1025 mL | 10.5126 mL | 21.0252 mL | |
| 5 mM | 0.4205 mL | 2.1025 mL | 4.2050 mL | |
| 10 mM | 0.2103 mL | 1.0513 mL | 2.1025 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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