benzyl N-[(1S)-3-methyl-1-{[(1S)-3-methyl-1-{[(2S)-4-methyl-1-oxopentan-2-yl]carbamoyl}butyl]carbamoyl}butyl]carbamate

• ChemBase ID: 73098
• Molecular Formular: C26H41N3O5
• Molecular Mass: 475.62084
• Monoisotopic Mass: 475.30462143
• SMILES: c1ccc(cc1)COC(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C=O)CC(C)C)CC(C)C
• Canonical SMILES: O=C[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)OCc1ccccc1)CC(C)C)CC(C)C)CC(C)C
• InChI: 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
• InChIKey: TZYWCYJVHRLUCT-VABKMULXSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: benzyl N-[(1S)-3-methyl-1-{[(1S)-3-methyl-1-{[(2S)-4-methyl-1-oxopentan-2-yl]carbamoyl}butyl]carbamoyl}butyl]carbamate
• IUPAC Traditional name: benzyl N-[(1S)-3-methyl-1-{[(1S)-3-methyl-1-{[(2S)-4-methyl-1-oxopentan-2-yl]carbamoyl}butyl]carbamoyl}butyl]carbamate
• Synonyms: MG-132; MG132; MG132; Z-Leu-Leu-Leu-al

Database IDs

• CAS Number: 133407-82-6
• MDL Number: MFCD00674886
• PubChem SID: 24892475; 162038018
• PubChem CID: 462382

CALCULATED PROPERTIES

• Acid pKa: 12.466964
• H Acceptors: 4
• H Donor: 3
• LogD (pH = 5.5): 4.114576
• LogD (pH = 7.4): 4.1145725
• Log P: 4.114576
• Molar Refractivity: 130.8675 cm^3
• Polarizability: 51.56013 Å^3
• Polar Surface Area: 113.6 Å^2
• Rotatable Bonds: 15
• Lipinski's Rule of Five: true

PROPERTIES

Physical Property

• Solubility: DMSO: soluble
• Apperance: powder

Safety Information

• Storage Condition: -20°C
• German water hazard class: 3
• Personal Protective Equipment: Eyeshields, Gloves, type N95 (US), type P1 (EN143) respirator filter
• Storage Temperature: -20°C

Pharmacology Properties

• Target: Proteasome
• Gene Information: human ... CTSB(1508), NFKB1(4790), PSMA1(5682)

Product Information

• Purity: ≥90% (HPLC)
• Salt Data: Free Base
• Quality: proteasome inhibition tested

DETAILS

Selleck Chemicals - S2619

Research Area

• Description: Cancer

Protocol

• Protocol: Kinase Assay ^[1]
• Measurement of inhibitory activities of MG-132 against 20S proteasome: The reaction mixture for the 20S proteasome inhibitory assay contains 0.1 M Tris-acetate, pH 7.0, 20S proteasome, MG-132, and 25 μM substrate dissolved in dimethyl sulfoxide in a final volume of 1 mL. After incuba tion at 37 °C for 15 minutes, the reaction is stopped by the addition of 0.1 mL of 10% SDS and 0.9 mL of 0.1M Tris acetate, pH 9.0. The fluorescence of the reaction products is measured. To determine the IC50 against 20S proteasome, various concentrations of MG-132 are included in the assay mixture.
• Protocol: Cell Assay ^[5]
• Cell Lines: KIM-2, HC11, and ES
• Concentrations: Dissolved in DMSO, final concentrations ~25 μM
• Incubation Time: 24, and 48 hours
• Methods: Cells are exposed to various concentrations of MG-132 for 24, and 48 hours. Supernatant and monolayer cells are harvested by centrifugation and fixed in 70% ethanol in PBS for staining with acridine orange. Equal volumes of cells and acridine orange (5 mg/mL in PBS) are mixed on a microscope slide and examined by fluorescence microscopy. For annexin V analysis, cells are harvested by centrifugation and stained with annexin V and propidium iodide. For cell cycle analysis, cells are rehydrated in PBS at room temperature for 10 minutes, followed by staining with propidium iodide (5 mg/mL). All samples are analyzed using a Coulter Epics XL flow cytometer.
• Protocol: Animal Study ^[6]
• Animal Models: Male mdx (C57BL/10ScSn DMD mdx) mice
• Formulation: Dissolved in DMSO, and diluted in PBS
• Doses: ~10 μg/kg/day
• Administration: Injection

References

• References: [1] Tsubuki S, et al. J Biochem, 1996, 119(3), 572-576.
• References: [2] Fiedler MA, et al. Am J Respir Cell Mol Biol, 1998, 19(2), 259-268.
• References: [3] Giuliano M, et al. Cancer Res, 1999, 59(21), 5586-5595.
• References: [4] Arlt A, et al. Oncogene, 2001, 20(7), 859-868.
• References: [5] MacLaren AP, et al. Cell Death Differ, 2001, 8(3), 210-218.
• References: [6] Bonuccelli G, et al. Am J Pathol, 2003, 163(4), 1663-1675.

Sigma Aldrich - C2211

Amino Acid Sequence
Z-Leu-Leu-Leu-al
Frequently Asked Questions
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Biochem/physiol Actions
Potent, membrane-permeable proteasome inhibitor. Induces neurite outgrowth in PC12 cells at 10 μM. Blocks cleavage of poly(ADP-ribose) polymerase and apoptosis in thymocytes. Proteasome inhibition induces accumulation of heat shock protein mRNA, activation of heat-shock proteins, and enhanced thermotolerance in various cell types: however, it also activates JNK-1, which initiates apoptosis in response to cell stress.

REFERENCES

• Tsubuki S, et al. J Biochem, 1996, 119(3), 572-576.
• Fiedler MA, et al. Am J Respir Cell Mol Biol, 1998, 19(2), 259-268.
• Giuliano M, et al. Cancer Res, 1999, 59(21), 5586-5595.
• Arlt A, et al. Oncogene, 2001, 20(7), 859-868.
• MacLaren AP, et al. Cell Death Differ, 2001, 8(3), 210-218.
• Bonuccelli G, et al. Am J Pathol, 2003, 163(4), 1663-1675.