(S)-MG132

Ubiquitin-proteasome inhibitor; NF-kB pathway inhibitor; IκB activator

(S)-MG132

Ubiquitin-proteasome inhibitor; NF-kB pathway inhibitor; IκB activator

From: 28 USD
Catalog #
73262_C
Ubiquitin-proteasome inhibitor; NF-kB pathway inhibitor; IκB activator

Overview

(S)-MG132 is a reversible, cell-permeable inhibitor of proteasome activity (IC₅₀ = 100 nM; Kisselev & Goldberg) and calpain (IC₅₀ = 1.2 µM; Tsubuki et al.). The ubiquitin-proteasome pathway selectively degrades intracellular proteins, thereby clearing damaged or misfolded proteins, and regulating the availability of key proteins involved in the control of inflammatory processes and cell cycle regulation. (S)-MG132 suppresses NF-κB activation by preventing IκB degradation (IC₅₀ = 3 µM; Arlt et al., Palombella et al., Ortiz-Lazareno et al.).

CANCER RESEARCH
· Blocks apoptosis triggered by DNA damage in HeLa cells (Zhang et al.).
· Inhibits NF-κB activation, sensitizing a variety of carcinoma cell lines to apoptosis (Arlt et al.).
· Cytotoxic effects on a variety of human cancer cell lines (Banerjee & Liefshitz).
· Inhibits growth of mouse melanoma (B16) and human ocular melanoma (IPC227F) cell lines (Vivier et al.).
Alternative Names
Z-Leu-Leu-Leu-CHO; Calpain inhibitor IV-2
Cell Type
Cancer Cells and Cell Lines
Species
Human, Mouse, Rat, Non-Human Primate, Other
Area of Interest
Cancer
CAS Number
133407-82-6
Chemical Formula
C₂₆H₄₁N₃O₅
Molecular Weight
475.6 g/mol
Purity
≥ 98%
Pathway
NF-κB, Ubiquitin
Target
IκB, Proteasome

Protocols and Documentation

Find supporting information and directions for use in the Product Information Sheet or explore additional protocols below.

Document Type
Product Name
Catalog #
Lot #
Language
Product Name
(S)-MG132
Catalog #
73262, 73264
Lot #
All
Language
English
Document Type
Safety Data Sheet
Product Name
(S)-MG132
Catalog #
73262, 73264
Lot #
All
Language
English

Resources and Publications

Educational Materials (2)

Publications (8)

MG132 inhibition of proteasome blocks apoptosis induced by severe DNA damage. Zhang L et al. Cell cycle (Georgetown, Tex.) 2011

Abstract

The 26S proteasome, a multicatalytic enzyme complex, is the main intracellular proteolytic system involved in the degradation of ubiquitinated proteins. The ability of proteasome inhibitors to induce apoptosis has been exploited in the recent development of chemotherapeutic agents. Here, we show that inhibition of proteasome by MG132 blocks DNA damage-induced apoptosis. Blockage of apoptosis by MG132 correlates with p53 stabilization and upregulation of p21/WAF1, a p53 transcriptional target. Surprisingly, in the absence of MG132, robust apoptosis induced by a high dose of UV irradiation correlate with rapid p53 degradation. This is in sharp contrast to p53 stabilization when cells were exposed to lower levels of UV irradiation. Our findings highlight a scenario in which severe UV damage can induce rapid p53 degradation by the proteasome. Importantly, these data suggest that the 26S proteasome plays a key role in promoting apoptosis induced by high doses of UV irradiation.
Synthesis, radiosynthesis, and biological evaluation of new proteasome inhibitors in a tumor targeting approach. Vivier M et al. Journal of medicinal chemistry 2008

Abstract

Proteasome inhibition is a new strategy in cancer therapy. We synthesized three new peptide aldehyde inhibitors linked to the benzamide derivative structure to use their cytotoxic activity against malignant melanoma cells. Of these, 10 displayed the highest cytotoxicity (0.18 +/- 0.16 microM). A radiosynthesis of the iodine aldehyde was performed. Its drug biodistribution showed that some selectivity of the benzamide group toward malignant melanoma tissue was conserved.
MG132 proteasome inhibitor modulates proinflammatory cytokines production and expression of their receptors in U937 cells: involvement of nuclear factor-kappaB and activator protein-1. Ortiz-Lazareno PC et al. Immunology 2008

Abstract

In response to inflammatory stimuli, monocytes/macrophages secrete greater quantities of the proinflammatory cytokines tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and IL-6. The inflammatory process and the innate immune response are related to the activation of several transcription factors, such as nuclear factor kappaB (NF-kappaB) and activator protein 1 (AP-1). The proteasome is a multimeric protease complex, which plays a vital role in several cellular functions, including the regulation of transcription factors like NF-kappaB. In this study, we used the human monocyte cell line U937 stimulated with lipopolysaccharide (LPS) and phorbol 12-myristate 13-acetate (PMA) as a model to investigate the in vitro effects of MG132, a proteasome inhibitor, on the release of TNF-alpha, IL-1beta and IL-6 and on the expression of their membrane and soluble receptors TNF-R1, IL-1R1 and IL-6R. We also analysed the effects of MG132 on the activation of NF-kappaB and AP-1 and on the IkappaB molecule. MG132 significantly inhibited the secretion of those proinflammatory cytokines. MG132 increased the release of the soluble receptors TNF-R1 and IL-1R1 from U937 cells and decreased their cell-surface expression. MG132 also increased IL-6R cell-surface expression and decreased its release. Proteasome inhibition also led to an increase in LPS+PMA-induced AP-1 activation and the attenuation of LPS+PMA-induced IkappaB degradation, resulting in the abolition of NF-kappaB activation. Our experiments strongly suggest that the proteasome is an important factor in the regulation of proinflammatory cytokines and their receptors.

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