MG-132

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C26H41N3O5
Molecular Weight	475.6208
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)C[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)OCC1=CC=CC=C1)C=O

InChI

InChIKey=TZYWCYJVHRLUCT-VABKMULXSA-N

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

HIDE SMILES / InChI

Molecular Formula	C26H41N3O5
Molecular Weight	475.6208
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	3 / 3
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/11514224 | https://www.ncbi.nlm.nih.gov/pubmed/19513526 | https://www.ncbi.nlm.nih.gov/pubmed/8830056

MG-132, also known as carbobenzoxy-Leu-Leu-leucinal, is a peptide aldehyde, which effectively blocks the proteolytic activity of the 26S proteasome complex. It also strongly inhibited calpain activity in vitro. MG-132 is used as a tool for perturbing the proteasome-regulated degradation of intracellular proteins.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Proteasome Macropain subunit MB1 4 Target ID: CHEMBL4662 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11514224	Inhibitor 8504	0.00185 µM [Ki]
Proteasome Macropain subunit 2 Target ID: CHEMBL3492 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11514224	Inhibitor 8504
Proteasome subunit beta type-6 2 Target ID: CHEMBL1944496 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11514224	Inhibitor 8504	0.235 µM [Ki]
Cathepsin B 9 Target ID: CHEMBL4072 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11514224	Inhibitor 8504	0.006 µM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Unknown 2596

PubMed

Title	Date	PubMed
TDP-43 causes differential pathology in neuronal versus glial cells in the mouse brain.	2014-05-15	24381309
Broad-spectrum antimalarial activity of peptido sulfonyl fluorides, a new class of proteasome inhibitors.	2013-08	23689711
Proteasome inhibitors block HIV-1 replication by affecting both cellular and viral targets.	2009-07-17	19426715
The effect of MG132, a proteasome inhibitor on HeLa cells in relation to cell growth, reactive oxygen species and GSH.	2009-07	19513526
Inhibition of agonist-induced down-regulation of the delta-opioid receptor with a proteasome inhibitor attenuates opioid tolerance in human embryonic kidney 293 cells.	2007-03	17159161
Modulation of IgE-dependent COX-2 gene expression by reactive oxygen species in human neutrophils.	2006-07	16624933
Optimization of subsite binding to the beta5 subunit of the human 20S proteasome using vinyl sulfones and 2-keto-1,3,4-oxadiazoles: syntheses and cellular properties of potent, selective proteasome inhibitors.	2006-05-18	16686537
Proteasome-dependent degradation of cytochromes P450 2E1 and 2B1 expressed in tetracycline-regulated HeLa cells.	2004-09-15	15364548
Inhibition of the proteasome reduces transfer-induced diabetes in nonobese diabetic mice.	2004-07-09	15238082
A novel structural class of potent inhibitors of NF-kappa B activation: structure-activity relationships and biological effects of 6-aminoquinazoline derivatives.	2003-09-01	12927847
Potential of the proteasomal inhibitor MG-132 as an anticancer agent, alone and in combination.	2002-03-26	11911275
Proteasome inhibition interferes with gag polyprotein processing, release, and maturation of HIV-1 and HIV-2.	2000-11-21	11087859
Potent and selective inhibitors of the proteasome: dipeptidyl boronic acids.	1998-02-17	9871680
Differential inhibition of calpain and proteasome activities by peptidyl aldehydes of di-leucine and tri-leucine.	1996-03	8830056

Patents

Sample Use Guides

In Vivo Use Guide

Unknown

Route of Administration: Unknown

In Vitro Use Guide

Dose-dependent inhibition of cell growth was observed in HeLa cells with an IC50 of approximately 5 microM MG-132 for 24 h. DNA flow cytometric analysis indicated that treatment with MG132 induced S, G2-M or non-specific phase arrests of the cell cycle dose-dependently. Treatment with MG132 induced apoptosis in a dose-dependent manner, as evidenced by sub-G1 cells and annexin V staining cells. Treatment with MG132 also induced the loss of mitochondrial membrane potential in HeLa cells. MG132 inhibited the growth of HeLa cells via inducing the cell cycle arrest as well as triggering apoptosis.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 22:43:58 GMT 2025` Edited by `admin` on `Mon Mar 31 22:43:58 GMT 2025`
Record UNII	RF1P63GW3K
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

MG-132

Common Name

English

CARBOBENZOXY-LEUCYL-LEUCYL-LEUCINAL

Preferred Name

English

Z-LEU-LEU-LEUCINAL

Common Name

English

BENZYLOXYCARBONYLLEUCYL-LEUCYL-LEUCINE ALDEHYDE

Systematic Name

English

Z-LEU-LEU-LEU-AL

Common Name

English

Code System Code Type Description

FDA UNII

RF1P63GW3K