Ixazomib citrate [MLN9708]

Synthetic. Chemical. CAS: 1239908-20-3. Formula: C20H23BCl2N2O9. MW: 517.1. Synthetic. Potent selective and reversible proteasome inhibitor (all proteolytic subunits). Targets the chymotrypsin-like beta5 subunit of the constitutive 20S proteasome (IC50=3.4nM). Cross-reacts and inhibits the trypsin-like beta2 subunit (IC50=3.5µM) and the caspase-like/peptidyl-glutamyl peptide-hydrolyzing (PGPH) beta1 subunit (IC50=0.03µM). Anticancer compound effective in cell-based assays, in xenografts and against multiple myeloma in vivo. In vitro, induces cell cycle arrest and apoptosis in human cancer cell lines including multiple myeloma. Prodrug that rapidly hydrolyzes to MLN2238 (AG-CR1-3670). Exhibits improved pharmacodynamics and antitumor activity compared to bortezomib in various B-cell lymphoma models, due to a greater tumor to blood ratio of proteasome inhibition that ultimately translates into improved tumor pharmacodynamic response and antitumor activity in several tumor xenograft models.