Ixazomib Citrate (MLN-9708)

Cas No.:	1239908-20-3
Chemical Name:	Ixazomib citrate
Synonyms:	MLN9708; MLN-9708; MLN 9708; ixazomib citrate. MMLN-2238-prodrug. MMLN 2238-prodrug; MMLN2238-prodrug; Ixazomib-prodrug; Ninlaro.
SMILES:	B1(OC(=O)CC(O1)(CC(=O)O)C(=O)O)[C@H](CC(C)C)NC(=O)CNC(=O)C2=C(C=CC(=C2)Cl)Cl
Formula:	C20H23BCl2N2O9
M.Wt:	517.122
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	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.
In Vivo:	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[2].
In Vitro:	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[1].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[2].