| 产品描述： | Ixazomib citrate (MLN9708) is a reversible inhibitor of the chymotrypsin-like proteolytic β5 site of the 20S proteasome with an IC50 of 3.4 nM and a Ki of 0.93 nM |
| 靶点： |
IC50: 3.4 nM (20S proteasome β5), 31 nM (20S proteasome β1), 3500 nM (20S proteasome β2);Proteasome; Autophagy |
| 体外研究： |
Ixazomib citrate (MLN9708; 0.20-3.20 µM) inhibits the cell growth of both cell lines effectively in a time- and dose-dependent manner. Ixazomib induces cell cycle arrest in MG-63 and Saos-2 cells. Ixazomib induces apoptosis mainly through the caspases pathway and requires the activation of both caspase8 and caspase9. Ixazomib treatment increases the levels of pro-apoptotic proteins and down regulates the anti-apoptotic proteins that control MOMP. Ixazomib treatment induces the release of Cytc, Smac, OMI from mitochondria and decreases the protein levels of XIAP. Ixazomib inhibits the invasion ability of MG-63 and Saos-2 cells and decreases both the expression and secretion levels of MMP2/9.Ixazomib citrate (MLN9708; 12 nM) shows inhibitory activity against C-L and T-L proteasome activities. Treatment of H929 and MM.1S MM cells with Ixazomib triggers a marked increase in proteolytic cleavage of poly(ADP) ribose polymerase (PARP), a signature event during apoptosis. Ixazomib induces cleavage of caspase-3, an upstream activator of PARP. Ixazomib induces eIf2-α kinase activity and protein levels of Bip and CHOP/GADD153. Ixazomib blocks BMSCs-induced MM cell proliferation, inhibits in vitro capillary tubule formation, and target NF-κB |
| 体内研究： |
Ixazomib citrate (MLN9708; 11 mg/kg) significantly inhibits MM tumor growth and prolongs survival in the human plasmacytoma MM.1S xenograft mouse model. The blood chemistry profiles of Ixazomib-treated mice show normal levels of creatinine, hemoglobin, and bilirubin. Ixazomib dramatically increases the number of cleaved-caspase-3 positive cells of the xenograft model |
| 参考文献： |
1. Liu R, et al. A New Perspective for Osteosarcoma Therapy: Proteasome Inhibition by MLN9708/2238 Successfully Induces Apoptosis and Cell Cycle Arrest and Attenuates the Invasion Ability of Osteosarcoma Cells in Vitro. Cell Physiol Biochem. 2017 Jan 27;41(2 2. Chauhan D, et al. In vitro and in vivo selective antitumor activity of a novel orally bioavailable proteasome inhibitor MLN9708 against multiple myeloma cells. Clin Cancer Res. 2011 Aug 15;17(16):5311-21. 3. Kupperman E, et al. Evaluation of the proteasome inhibitor MLN9708 in preclinical models of human cancer. Cancer Res. 2010 Mar 1;70(5):1970-80. |
| 溶解性： |
Soluble in DMSO |
| 保存条件： |
-20℃ |
| 配置溶液浓度参考： |
|
1mg |
5mg |
10mg |
| 1 mM |
1.934 ml |
9.669 ml |
19.338 ml |
| 5 mM |
0.387 ml |
1.934 ml |
3.868 ml |
| 10 mM |
0.193 ml |
0.967 ml |
1.934 ml |
| 50 mM |
0.039 ml |
0.193 ml |
0.387 ml |
|
| 注意： |
部分产品我司仅能提供部分信息，我司不保证所提供信息的权威性，仅供客户参考交流研究之用。 |
上海工商
危险品化学品经营许可证（不带存储）
营业执照(三证合一)
北京