Ixazomib-citrate-MLN9708-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEIxazomib citrateCat. No.: HY-10452CAS No.: 1239908-20-3Synonyms: MLN9708分式: CHBClNO分量: 517.12作靶点: Proteasome; Autophagy作通路: Metabolic Enzyme/Protease; Autophagy储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 mon

2、th溶解性数据体外实验 DMSO : 100 mg/mL (193.38 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 1.9338 mL 9.6689 mL 19.3379 mL5 mM 0.3868 mL 1.9338 mL 3.8676 mL10 mM 0.1934 mL 0.9669 mL 1.9338 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。体内实验请根据您的实验动物和给药式选择适当的溶解案，

3、配制前请先配制澄清的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (4.83 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (4.83 mM); Clear solution

4、1/3 Master of Small Molecules 您边的抑制剂师www.MedChemE3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (4.83 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Ixazomib citrate (MLN9708)20S蛋酶体胰凝乳蛋酶样蛋解5位点的可逆抑制剂，IC50 为3.4 nM和Ki为0.93 nM。IC50 & Target IC50: 3.4 nM (20S proteasome 5), 31 nM (20S proteasome 1),

5、 3500 nM (20S proteasome 2) 3体外研究 Ixazomib citrate (MLN9708; 0.20-3.20 M) inhibits the cell growth of both cell lines effectively in a time- anddose-dependent manner. Ixazomib induces cell cycle arrest in MG-63 and Saos-2 cells. Ixazomib inducesapoptosis mainly through the caspases pathway and requi

6、res the activation of both caspase8 and caspase9.Ixazomib treatment increases the levels of pro-apoptotic proteins and down regulates the anti-apoptoticproteins that control MOMP. Ixazomib treatment induces the release of Cytc, Smac, OMI from mitochondriaand decreases the protein levels of XIAP. Ixa

7、zomib inhibits the invasion ability of MG-63 and Saos-2 cellsand decreases both the expression and secretion levels of MMP2/9 1.Ixazomib citrate (MLN9708; 12 nM)shows inhibitory activity against C-L and T-L proteasome activities. Treatment of H929 and MM.1S MM cellswith Ixazomib triggers a marked in

8、crease in proteolytic cleavage of poly(ADP) ribose polymerase (PARP), asignature event during apoptosis. Ixazomib induces cleavage of caspase-3, an upstream activator of PARP.Ixazomib induces eIf2- kinase activity and protein levels of Bip and CHOP/GADD153. Ixazomib blocksBMSCs-induced MM cell proli

9、feration, inhibits in vitro capillary tubule formation, and target NF-B 2.体内研究 Ixazomib citrate (MLN9708; 11 mg/kg) significantly inhibits MM tumor growth and prolongs survival in thehuman plasmacytoma MM.1S xenograft mouse model. The blood chemistry profiles of Ixazomib-treated miceshow normal leve

10、ls of creatinine, hemoglobin, and bilirubin. Ixazomib dramatically increases the number ofcleaved-caspase-3 positive cells of the xenograft model 2.PROTOCOLCell Assay 1 Cell viability is assessed using the MTT assay. Cells are trypsinized and seeded in 96-well plate at 5000 cellsper well. Cells are

11、treated with Ixazomib or DMSO in basal medium at the indicated doses and times. Cellviability is determined relative to control cells treated with vehicle alone.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Ixazomib is dissolved in 5% 2-hydroxy

12、propyl- cyclodextrin at 2 mg/mL concentration. The humanAdministration 2 plasmacytoma xenograft tumor model is used in the assay. CB-17 SCID mice (n=21) are subcutaneouslyinoculated with 5.0106 MM.1S cells in 100 L serum-free RPMI-1640 medium, and randomized to treatmentgroups when tumors reach 250-

13、300 mm3. Mice are treated with vehicle, bortezomib (1 mg/kg; i.v) orIxazomib (11 mg/kg; i.v) twice weekly for 3 weeks. Animals are euthanized when their tumors reach 2 cm3.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES2/3 Master of Small Mol

14、ecules 您边的抑制剂师www.MedChemE1. Liu R, et al. A New Perspective for Osteosarcoma Therapy: Proteasome Inhibition by MLN9708/2238 Successfully Induces Apoptosisand Cell Cycle Arrest and Attenuates the Invasion Ability of Osteosarcoma Cells in Vitro. Cell Physiol Biochem. 2017 Jan 27;41(22. Chauhan D, et

15、al. In vitro and in vivo selective antitumor activity of a novel orally bioavailable proteasome inhibitor MLN9708 againstmultiple 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.