133407-82-6 Usage
Description
MG-132 is a potent, reversible, and cell-permeable proteasome inhibitor with a Ki value of 4 nM. It is a specific inhibitor of the chymotrypsin-like activity of the 20S proteasome and also inhibits calpain. MG-132 reduces the degradation of ubiquitin-conjugated proteins in mammalian cells and yeast strains without affecting their ATPase or isopeptidase activities. It activates stress kinases, induces heat shock protein 72 (Hsp72), and blocks NFκB activation by inhibiting IκB proteolysis. MG-132 is a tripeptide composed of L-leucyl-L-leucyl-L-leucine, with the C-terminal carboxy group reduced to the corresponding aldehyde and the N-terminal amino group protected as its benzyloxycarbonyl derivative.
Uses
Used in Pharmaceutical Industry:
MG-132 is used as a proteasome and NF-κB inhibitor for its ability to suppress gastric cancer cell proliferation, induce macro-autophagy, and activate stress kinases.
Used in Neuroprotection:
MG-132 is used as a neuroprotective product due to its ability to induce neurite outgrowth in PC12 cells and block NFκB activation, which can be beneficial in treating neurodegenerative diseases.
Used in Research Applications:
MG-132 is used as a research tool to study the role of proteasomes and NF-κB in various cellular processes, as well as to investigate the effects of proteasome inhibition on protein degradation and cellular signaling pathways.
Biological Activity
Potent cell-permeable inhibitor of proteasome (IC 50 = 100 nM) and calpain (IC 50 = 1.2 μ M). Inhibits TNF- α -induced NF- κ B activation and I κ B α degradation. Induces neurite outgrowth in PC12 cells and has anticancer properties in vitro .
Biochem/physiol Actions
Cell permeable: yes
References
1) Tsubuki et al. (1996), Differential inhibition of calpain and proteasome activities by peptidyl aldehydes of di-leucine and tri-leucine; J. Biochem.,? 119 572
2) Wu? et al. (2010), Macroautophagy and ERK phosphorylation counteract the antiproliferative effect of proteasome inhibitor in gastric cancer cells; Autophagy, 6 228
3) Meriin? et al. (1998), Proteasome inhibitors activate stress kinases and induce Hsp72. Diverse effects on apoptosis; J. Biol. Chem., 273 6373
4) Fiedler et al. (1998), Inhibition of TNF-alpha-induced NF-kappaB activation and IL-8 release in A549 cells with the proteasome inhibitor MG-132; Am. J. Respir. Cell Mol. Biol., 19 259
Check Digit Verification of cas no
The CAS Registry Mumber 133407-82-6 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,3,3,4,0 and 7 respectively; the second part has 2 digits, 8 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 133407-82:
(8*1)+(7*3)+(6*3)+(5*4)+(4*0)+(3*7)+(2*8)+(1*2)=106
106 % 10 = 6
So 133407-82-6 is a valid CAS Registry Number.
InChI:InChI=1/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
133407-82-6Relevant articles and documents
Application of proteasome inhibitor in inhibition of novel coronavirus
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Paragraph 0130; 0146-0148, (2021/06/22)
The invention provides application of a proteasome inhibitor in inhibition of a novel coronavirus or preparation of novel coronavirus inhibitors. The proteasome inhibitor has a structure represented by a formula (I) or isomers, pharmaceutically acceptable salts thereof and prodrugs thereof. According to the application, by applying the proteasome inhibitor to inhibition of the novel coronavirus, good inhibiting activity is obtained, and a novel treatment way of think is provided for diseases such as pneumonia caused by the novel coronavirus.
Systematic comparison of peptidic proteasome inhibitors highlights the α-ketoamide electrophile as an auspicious reversible lead motif
Stein, Martin L.,Cui, Haissi,Beck, Philipp,Dubiella, Christian,Voss, Constantin,Krueger, Achim,Schmidt, Boris,Groll, Michael
supporting information, p. 1679 - 1683 (2014/03/21)
The ubiquitin-proteasome system (UPS) has been successfully targeted by both academia and the pharmaceutical industry for oncological and immunological applications. Typical proteasome inhibitors are based on a peptidic backbone endowed with an electrophi
Synthesis and SAR study of novel peptide aldehydes as inhibitors of 20S proteasome
Ma, Yuheng,Xu, Bo,Fang, Yuan,Yang, Zhenjun,Cui, Jingrong,Zhang, Liangren,Zhang, Lihe
scheme or table, p. 7551 - 7564 (2011/11/14)
Based on the analysis of the crystal structure of MG101 (1) and 20S proteasomes, a new series of peptide aldehyde derivatives were designed and synthesized. Their ability to inhibit 20S proteasome was assayed. Among them, Cbz-Glu(OtBu)-Phe-Leucinal (3c), Cbz-Glu(OtBu)-Leu-Leucinal (3d), and Boc-Ser(OBzl)-Leu-Leucinal (3o) exhibited the most activity, which represented an order of magnitude enhancement compared with MG132 (2). The covalent docking protocol was used to explore the binding mode. The structure-activity relationship of the peptide aldehyde inhibitors is discussed.