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Proteasome inhibitors
MG132
Другие языки:

MG132

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MG132
MG132.svg
Names
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)
ChemSpider
PubChem CID
UNII
  • 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 ☒N
    Key: TZYWCYJVHRLUCT-VABKMULXSA-N ☒N
  • CC(C)C[C@@H](C=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)OCc1ccccc1
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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MG132 is a potent, reversible, and cell-permeable proteasome inhibitor (Ki = 4 nM). It belongs to the class of synthetic peptide aldehydes. 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.

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). These are substrate analogues and potent transition-state inhibitors of chymotrypsin like activity of proteasome machinery. 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.

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