MG-132

MG-132 (Z-Leu-leu-leu-al, Zlllal) is a potent, reversible, and cell-permeable proteasome inhibitor with IC50 of 0.1 and 1.2 μM for the inhibition of proteasome and calpain, respectively; induces neurite outgrowth in PC12 cells with optimal concentrations of 20 nM, inhibits autolytic activation of calpain in rabbit erythrocytes at 100 uM; demonstrates in vivo antitumor activity.(In Vitro):MG-132 (Z-Leu-Leu-Leu-al) initiates neurite outgrowth in PC12 cells at a low concentration (30 nM) and is a very strong inhibitor of 20S proteasome.MG-132 (10 μM; 1 hour) reverses the effects of TNF- α on I κ B degradation and NF-κ B activation in A549 cells.MG-132 (0.75-5 μM; 24 hours) potently induces p53-dependent apoptosis in KIM-2 cells by 26S proteasome inhibition.MG-132 (10-40 μM; 24 hours) significantly reduces the viability of C6 glioma cells in both time- and concentration-dependent manners and shows the IC50 of 18.5 μM at 24 hours.MG-132 (18.5 μM; 24 hours) induces down-regulation of anti-apoptotic proteins Bcl-2 and XIAP and up-regulates expression of pro-apoptotic protein Bax and caspase-3.(In Vivo):MG132 (10 mg/kg; i.p.; daily for 25 days starting 5 days after EC9706 cells injection) significantly inhibits tumor growth of the EC9706 xenograft without causing toxicity to mice.MG-132 (1 mg/kg; i.v.; twice a week for 4 weeks) shows potent tumor inhibitory effect against mice bearing HeLa tumors.MG-132 (1-10 μg/kg/24 hours; subcutaneously implanted osmotic pumps; for 8 days) greatly increases the expression levels of β-dystroglycan, α-dystroglycan, α-sarcoglycan, and dystrophin in skeletal muscle lysates in mice (six-month-old male C57BL/10ScSn DMD mdx mice).