| Identification | Back Directory | [Name]
Z-Leu-Leu-Leu-B(OH)2 (MG262) | [CAS]
179324-22-2 | [Synonyms]
Z-Leu-Leu-Leu-B(OH)2 (MG262)
Proteasome Inhibitor III - Calbiochem
L-Leucinamide, N-[(phenylmethoxy)carbonyl]-L-leucyl-N-[(1R)-1-borono-3-methylbutyl]-
[(1R)-3-methyl-1-[[(2S)-4-methyl-2-[[(2S)-4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]pentanoyl]amino]butyl]boronic acid | [Molecular Formula]
C25H42BN3O6 | [MDL Number]
MFCD02179373 | [MOL File]
179324-22-2.mol | [Molecular Weight]
491.43 |
| Chemical Properties | Back Directory | [density ]
1.101±0.06 g/cm3(Predicted) | [storage temp. ]
-20C | [solubility ]
≥24.57 mg/mL in DMSO; insoluble in H2O; ≥96.4 mg/mL in EtOH | [form ]
White solid | [pka]
9.69±0.43(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
MG-262 (Z-Leu-Leu-LeuB(OH)2; ZL3B) is a reversible proteasome inhibitor. MG-262 down-regulates VEGF receptor Flt-1. MG-262 inhibits cell growth and induces apoptosis in malignant cells. MG-262 induces reactive oxygen species (ROS). MG-262 can be used for anti-cancer study[1][2][3][4][5]. | [General Description]
A boronic acid-based, reversible proteasome inhibitor that is structurally similar to MG-132 (Cat. No. 474790) but displays much higher potency (Ki = 0.03 nM versus 4 nM for MG-132). | [Biological Activity]
mg-262 (also known as z-leu-leu-leu-b(oh)2), a boronic peptide acid, is a potent proteasome inhibitor that selectively and reversibly inhibits the chymotryptic activity of the proteasome. it consists of a peptide and boronic acid moiety which are functional to proteasome inhibition. according to previous studies, mg-262 is capable of reducing the viability of nasal mucosa and polyp fibroblasts, provoking cell growth arrest, inhibiting dna replication and retinoblastoma phosphorylation, increasing expression of the cell cycle inhibitor p21 and p27, and inducing cell death via loss of mitochondrial membrane potential, caspase-3 and poly(adp-ribose) polymerase activation, induction of c-jun phosphorylation and mitogen-activated protein kinase phosphatase-1 expression.laura pujols, laura fernandez-bertolin, mireya fuentes-prado, isam alobid, jordi roca-ferrer, neus agell, joaquim mullol, and cesar picado. proteasome inhibition reduces proliferation, collagen expression, and inflammatory cytokine production in nasal mucosa and polyp fibroblasts. the journal of pharmacology and experimental therapeutics 2012; 343:184-197hilary frase, jason hudak, and irene lee. identification of the proteasome inhibitor mg262 as a potent atp-dependent inhibitor of the salmonella enteric serovar typhimurium lon protease. biochemistry 2006; 45 (27): 8264-8274 | [Biochem/physiol Actions]
Target Ki: 30 pM against proteasome | [in vivo]
MG-262 (5 μmol/kg (2.5 mg/kg); i.v.; 20 hours before collecting tissue samples) accumulates GFPdgn protein[4].
MG-262 (1-5 μmol/kg (0.5-2.5 mg/kg); i.p.; 20 h before the test) accumulates the GFP reporter in the liver, indicating substantial impairment of the ubiquitin/proteasome system in UbG76V-GFP/1 mice[5].
| Animal Model: | UbG76V-GFP/1 mice (The transgenic construct was injected into fertilized CBA × C57BL/6 F1 oocytes. Transgenic founders were backcrossed to C57BL/6 mice)[5] | | Dosage: | 1, 5 μmol/kg (0.5, 2.5 mg/kg) | | Administration: | Intraperitoneal injection (i.p.); 20 h before test | | Result: | Fluorescent cells were detected exclusively in the livers, resulted in accumulation of GFP in the vast majority of hepatocytes distributed throughout the live.
A dose-dependent decrease of the chymotrypsin-like activity of the proteasome was observed in lysates of the liver, kidney and spleen.
|
| Animal Model: | Transgenic mice (ubiquitously expresses a surrogate protein substrate for the Ubiquitin-proteasome system, referred to as GFPdgn)[4] | | Dosage: | 5 μmol/kg (2.5 mg/kg) | | Administration: | Intravenous injection (i.v.); 20 h before the tissue samples were collected | | Result: | Inhibited chymotryptic activity in the heart, lungs, skeletal (Sk.) muscle, and liver by 50-75%.
GFPdgn levels in all the indicated organs clearly displayed significant increases.
|
| [References]
[1] Mezquita J, et al. Down-regulation of Flt-1 gene expression by the proteasome inhibitor MG262. J Cell Biochem. 2003 Aug 15;89(6):1138-47. DOI:10.1002/jcb.10587
[2] Wu HM, et al. Proteasome inhibitors stimulate activator protein-1 pathway via reactive oxygen species production. FEBS Lett. 2002 Aug 28;526(1-3):101-5. DOI:10.1016/s0014-5793(02)03151-4
[3] Huang H, et al. Gambogic acid enhances proteasome inhibitor-induced anticancer activity. Cancer Lett. 2011 Feb 28;301(2):221-8. DOI:10.1016/j.canlet.2010.12.015
[4] Kumarapeli AR, et al A novel transgenic mouse model reveals deregulation of the ubiquitin-proteasome system in the heart by doxorubicin. FASEB J. 2005 Dec;19(14):2051-3. DOI:10.1096/fj.05-3973fje
[5] Lindsten K, et al. A transgenic mouse model of the ubiquitin/proteasome system. Nat Biotechnol. 2003 Aug;21(8):897-902. DOI:10.1038/nbt851 |
|
| Company Name: |
Sigma-Aldrich
|
| Tel: |
021-61415566 800-8193336 |
| Website: |
https://www.sigmaaldrich.cn |
| Company Name: |
Merck KGaA
|
| Tel: |
21-20338288 |
| Website: |
www.sigmaaldrich.cn |
|