Structure of MG-132
CAS No.: 133407-82-6
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
MG-132 is an inhibitor of proteasome (IC50 = 100 nM) and calpain (IC50 = 1.2 nM).
Synonyms: Z-Leu-Leu-Leu-al; Z-Leu-Leu-Leu-CHO; MGI-132
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Jiang, Huaji ; Xie, Yingchao ; Hu, Zhiqiang ; Lu, Jiansen ; Zhang, Jiahuan ; Li, Hongyu , et al.
Abstract: Inflammatory bowel disease (IBD) is a chronic and potentially life-threatening inflammatory disease of gastroenteric tissue characterized by episodes of intestinal inflammation, but the underlying mechanisms remain elusive. Here, we explore the role and precise mechanism of VanGogh-like 2 (VANGL2) during the pathogenesis of IBD. VANGL2 decreases in IBD patients and dextran sulfate sodium (DSS)-induced colitis in mice. Myeloid VANGL2 deficiency exacerbates the progression of DSS-induced colitis in mice and specifically enhances the activation of NLRP3 inflammasome in macrophages. NLRP3-specific inhibitor MCC950 effectively alleviates DSS-induced colitis in VANGL2 deficient mice. Mechanistically, VANGL2 interacts with NLRP3 and promotes the autophagic degradation of NLRP3 through enhancing the K27-linked polyubiquitination at lysine 823 of NLRP3 by recruiting E3 ligase MARCH8, leading to optineurin (OPTN)-mediated selective autophagy. Notably, decreased VANGL2 in the peripheral blood mononuclear cells from IBD patients results in overt NLRP3 inflammasome activation and sustained inflammation. Taken together, this study demonstrates that VANGL2 acts as a repressor of IBD progression by inhibiting NLRP3 inflammasome activation and provides insights into the crosstalk between inflammation and autophagy in preventing IBD.
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Zhiqiang Hu ; Yufen Zhang ; Yingchao Xie ; Jianwu Yang ; Haotian Tang ; Bolin Fan , et al.
Abstract: Toxoplasma gondii (T. gondii)-associated polymorphic effector proteins are crucial in parasite development and regulating host anti-T. gondii immune responses. However, the mechanism remains obscure. Here, it is shown that Toxoplasma effector dense granules 4 (GRA4) restricts host IFN-I activation. Infection with ∆gra4 mutant T. gondii strain induces stronger IFN-I responses and poses a severe threat to host health. Mechanistically, GRA4 binds to phosphorylated TBK1 to promote TRIM27-catalyzed K48-ubiquitination at Lys251/Lys372 residues, which enhances its recognition by autophagy receptor p62, ultimately leading to TBK1 autophagic degradation. Furthermore, an avirulent ∆gra4 strain (ME49∆ompdc/gra4) is constructed for tumor immunotherapy due to its ability to enhance IFN-I production. Earlier vaccination with ME49∆ompdc/gra4 confers complete host resistance to the tumor compared with the classical ME49∆ompdc treatment. Notably, ME49∆ompdc/gra4 vaccination induces a specific CD64 +MAR-1 +CD11b + dendritic cell subset, thereby enhancing T cell anti-tumor responses. Overall, these findings identify the negative role of T. gondii GRA4 in modulating host IFN-I signaling and suggest that GRA4 can be a potential target for the development of T. gondii vaccines and tumor immunotherapy.
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Keywords: attenuated T. gondii ; selective autophagy ; toxoplasmosis ; tumor therapy ; type I interferon
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CAS No. : | 133407-82-6 |
Formula : | C26H41N3O5 |
M.W : | 475.62 |
SMILES Code : | O=C(OCC1=CC=CC=C1)N[C@@H](CC(C)C)C(N[C@@H](CC(C)C)C(N[C@@H](CC(C)C)C=O)=O)=O |
Synonyms : |
Z-Leu-Leu-Leu-al; Z-Leu-Leu-Leu-CHO; MGI-132
|
MDL No. : | MFCD00674886 |
InChI Key : | TZYWCYJVHRLUCT-VABKMULXSA-N |
Pubchem ID : | 462382 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
In Vitro:
Cell Line
|
Concentration | Treated Time | Description | References |
MEFs | 10 µM | 1 h | MG132 was used to inhibit the proteasome activity, leading to analysis of STING pathway activation. | PMC9666523 |
MNs | 1 μM | 48 h | To explore the role of GSDME in motor neuron injury | PMC10121894 |
HEK293-EBNA | 10 µM | 24 h | The treatment was used to assess the effects on ubiquitination assays. | PMC9440122 |
Primary schwannoma cells | 10 µM | 3 h | Monitor proteasoma-dependent degradation. | PMC10115179 |
PDCCs | 4 µM | 6 days | MG-132 was used as a positive control for cell survival. | PMC9353492 |
293T cells | 20 μM | 7 h | To detect ubiquitination of proteins | PMC7854732 |
TuBo mammospheres | 10 µM | 8 h | To analyze the effect of MG132 on protein extraction from mammospheres. | PMC10175288 |
HEK293 cells | 20, 40, 80 μM | 4 h | Induction of proteasome stress | PMC8172468 |
iPSC derived cardiomyocytes | 10 μM | 3 h | Assess the effects of MG132 on hypoxia treatment in cardiomyocytes. | PMC8961225 |
A172 | 10 μM | 6 h | to suppress proteasome-mediated protein degradation | PMC9468590 |
HCT116, RKO | 20 μM | 6 h | To analyze the ubiquitination of proteins involved in NF-κB signaling. | PMC10850134 |
CS cells | 10 μM | 8 h | To analyze the expression of proteins; results showed significant differences based on statistical analysis. | PMC8257592 |
293T cells and NP cells | 10 μm | 8 h | The goal was to analyze GPX4 ubiquitination. This experimentation is implied but not explicitly detailed in the effects. | PMC10161035 |
HeLa cells | 10 μM | 6h | Explore the impact of MG132 on MARVELD1 and PARP1 interactions | PMC10070477 |
293T cells | 10μm | 48 h | MG132 is used to inhibit proteasome degradation and help determine the degradation pathway of mHTT. | PMC10625127 |
GIST cells | 20 μm | 8 h | To analyze the protein levels of USP5 and TRIM21. | PMC11425886 |
Jurkat cells | 50 μm | 8 h | To assess the degradation efficiency of PROTAC toolbox on targeted proteins. | PMC11220716 |
HCT116, HT29 | 1 μM | 24 h | To evaluate the effect of TKD on KRAS degradation in cancer cells. | PMC11211324 |
HepG2 | 20 μM | 6 h | To examine the ubiquitination of exogenous p53 protein. | PMC8386927 |
MDA-MB-231 | 10 μM | 6 h | MG132 was used to assess its effect on Vimentin expression and ubiquitination. | PMC7851937 |
HEK293T cells | 10 µM | 6 h | PMC9883464 | |
HGPS iPSC-derived VSMC | 1.25 µM | 24 h | MG-132 treatment significantly reduced progerin expression levels. | PMC5582415 |
HGPS fibroblasts | 5 µM | 24 h | MG-132 treatment significantly reduced progerin levels and promoted its degradation through autophagy. | PMC5582415 |
HepG2 cells | 0.3 μM | 24 h | Long-term treatment did not change LDLR mRNA but significantly increased LDLR protein by reducing PCSK9-mediated lysosome LDLR degradation. | PMC4125719 |
HepG2 cells | 0.3 μM | 8 h | Short-term treatment significantly increased LDLR mRNA and protein levels, which was blocked by PKC inhibitors. | PMC4125719 |
HepG2 cells | 0.03–3 μM | 24 h | MG132 dose-dependently increased LDLR mRNA and protein levels, as well as LDL uptake. | PMC4125719 |
HeLa cells | 10 µM | 16 hours | To evaluate the effect of Delanzomib on the plasma membrane expression of pathogenic pendrin variants. Results showed that Delanzomib significantly increased the plasma membrane expression levels of pathogenic pendrin variants. | PMC11913434 |
293 Phoenix cells | 1-10 µM | 16 hours | To evaluate the rescue effect of Delanzomib on the protein expression and ion transport function of pathogenic pendrin variants. Results showed that Delanzomib significantly increased the total protein levels and ion transport function of pathogenic pendrin variants. | PMC11913434 |
HEK293T cells | 10 µM | 6 hours | Proteasome inhibition MG132 stabilized PD-L1 during gallic acid treatment | PMC9274539 |
In Vivo:
Species
|
Animal Model
|
Administration | Dosage | Frequency | Description | References |
Mice | BALB/c nude mice | Subcutaneous injection | 10 mg/kg | weekly | To evaluate the effect of MG132 on tumor formation | PMC9596831 |
Mice | LmnaG609G/G609G mouse model | Intramuscular injections | 1 µg/kg and 10 µg/kg | Three times per week for 2 weeks | Local injection of MG-132 significantly reduced progerin and SRSF-1 levels without noticeable side effects. | PMC5582415 |
Bio Calculators | ||||
Preparing Stock Solutions | ![]() |
1mg | 5mg | 10mg |
1 mM 5 mM 10 mM |
2.10mL 0.42mL 0.21mL |
10.51mL 2.10mL 1.05mL |
21.03mL 4.21mL 2.10mL |
Tags: MG-132 | Z-Leu-Leu-Leu-al | Apoptosis Inducer | Protease Inhibitor | Carbamates | Esters | Proteasome | Organic Building Blocks | Apoptosis | Cell Apoptosis/Death Detection | Protease | Ubiquitin | Enzyme Inhibitors | 133407-82-6
Precautionary Statements-General | |
Code | Phrase |
P101 | If medical advice is needed,have product container or label at hand. |
P102 | Keep out of reach of children. |
P103 | Read label before use |
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Code | Phrase |
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P210 | Keep away from heat/sparks/open flames/hot surfaces. - No smoking. |
P211 | Do not spray on an open flame or other ignition source. |
P220 | Keep/Store away from clothing/combustible materials. |
P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
P230 | Keep wetted |
P231 | Handle under inert gas. |
P232 | Protect from moisture. |
P233 | Keep container tightly closed. |
P234 | Keep only in original container. |
P235 | Keep cool |
P240 | Ground/bond container and receiving equipment. |
P241 | Use explosion-proof electrical/ventilating/lighting/equipment. |
P242 | Use only non-sparking tools. |
P243 | Take precautionary measures against static discharge. |
P244 | Keep reduction valves free from grease and oil. |
P250 | Do not subject to grinding/shock/friction. |
P251 | Pressurized container: Do not pierce or burn, even after use. |
P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
P262 | Do not get in eyes, on skin, or on clothing. |
P263 | Avoid contact during pregnancy/while nursing. |
P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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