MG132
Chemical compound
From Wikipedia, the free encyclopedia
MG132 is a potent, reversible, and cell-permeable proteasome inhibitor[1] (Ki = 4 nM). It belongs to the class of synthetic peptide aldehydes.[2][3] It reduces the degradation of ubiquitin-conjugated proteins in mammalian cells and permeable strains of yeast by the 26S complex without affecting its ATPase or isopeptidase activities. MG132 activates c-Jun N-terminal kinase (JNK1), which initiates apoptosis. MG132 also inhibits NF-κB activation with an IC50 of 3 μM and prevents β-secretase cleavage.
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| Names | |
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| Systematic IUPAC name
Benzyl [(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 | |
| Other names
N-Benzyloxycarbonyl-L-leucyl-L-leucyl-L-leucinal Z-Leu-Leu-Leu-al | |
| Identifiers | |
3D model (JSmol) |
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PubChem CID |
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| UNII | |
CompTox Dashboard (EPA) |
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| Properties | |
| C26H41N3O5 | |
| Molar mass | 475.630 g·mol−1 |
| Appearance | White solid |
| Solubility | 100 mM in EtOH and DMSO |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Molecular mechanism
There are several inhibitors that can readily enter cell and selectively inhibit degradative pathway. It includes peptide aldehydes, such as Cbz-leu-leu-leucinal (MG132), Cbz-leu-leu-norvalinal (MG115) and acetyl-leu-leu-norleucinal (ALLN).[1] These are substrate analogues and potent transition-state inhibitors of chymotrypsin like activity of proteasome machinery.[4][5] The peptide aldehydes are also known to inhibit certain lysosomal cysteine proteases and the calpains hence MG132 may not be exclusive inhibitor of proteasomal pathway.[4]