MG-115,133407-86-0,IC-0233033

MG-115 is a potent inhibitor with Kis of 21 nM and 35 nM for 20S and 26S proteasome, respectively [1].
MG-115 (50 μM, 2 h) increased the expression of the insulin receptor and its mature beta subunit by a factor of 3 and 4.2, respectively in Leu1193 and Asp1179 COS-7 mutant cell lines[2].Treated Rat-1 and PC12 cells with MG-115(30 μM, 4 h) can induced apoptosis of both cell types[3]. Iisolated rat islets were cultured and pre-treated with proteasome inhibitors and subsequently exposed for 48 h to 25 U/ml human IL-1beta. Pre-treatment with 10 uM of the proteasome inhibitor MG-115 counteracted the suppressive effects[4]. HCC cells SK-Hep1, HLE and HepG2 were treated with the proteasome inhibitors MG-115. MG-115 induce apoptosis in the three cell types tested in a dose-dependent manner. MG-115 downregulated expression of XIAP in SK-Hep1, and survivin in SK-Hep1 and HepG2[5]. MG-115 decreased within 120 min the aldosterone and corticosterone secretion from freshly dispersed zona glomerulosa and zona fasciculata-reticularis (ZF/R) cells. After a 24-h incubation MG-115 alone lowered corticosterone production and enhanced proliferation rate of cultured ZF/R cells[6]. The proteasome inhibitor MG-115 can inhibit ATF6, which is the direct target of the proteasome-ubiquitin pathway[7]. MG-115 was diminished by adding at a time corresponding to the half time required for germinal vesicle breakdown. Potent inhibition of germinal vesicle breakdown was also observed by microinjection of anti-proteasome-a-subunit antibodies[8]. MG-115 induced a decrease in Bid, Bcl-2, and survivin protein levels, an increase in Bax, loss of the mitochondrial transmembrane potential, cytochrome c release, activation of caspases (-8, -9 and -3), and an increase in the tumor suppressor p53 levels in PC3[9].