MLN-9708, also known as ixazomib citrate, is a prodrug of Ixazomib (MMLN-2238). MLN-9708 is an orally bioavailable second generation proteasome inhibitor (PI) with potential antineoplastic activity. MLN-9708, after hydrolyzing to pharmacologically active MLN2238 (ixazomib), is a next-generation proteasome inhibitor with demonstrated preclinical and clinical antimyeloma activity. MLN-9708, compared with bortezomib, has improved pharmacokinetics, pharmacodynamics, and antitumor activity in preclinical studies.
CAS Number: 1239908-20-3
Molecular Weight: 517.12
Related CAS Number:
Chemical Name: 4-(carboxymethyl)-2-((R)-1-(2-(2,5-dichlorobenzamido)acetamido)-3-methylbutyl)-6-oxo-1,3,2-dioxaborinane-4-carboxylic acid
Appearance: Solid Power
Purity: ≥98% (or refer to the Certificate of Analysis)
Solubility: Solubility (25°C) DMSO: 100 mg/mL(193.37 mM). Water: Insoluble.
Shipping Condition: Shipped under ambien...
Storage Condition: Dry, dark and -20 oC...
Shelf Life: ≥12 months if stored properly.
Stock Solution Storage: 0 - 4 oC for 1 month or refer to the Certificate of Analysis.
Drug Formulation: To be determined.
HS Tariff Code: 382200
How to use
MLN-9708, 0.20-3.20 µM inhibits the cell growth of both cell lines effectively in a time- and dose-dependent manner. MLN-9708 induces cell cycle arrest in MG-63 and Saos-2 cells. MLN-9708 induces apoptosis mainly through the caspases pathway and requires the activation of both caspase8 and caspase9. MLN-9708 treatment increases the levels of pro-apoptotic proteins and down regulates the anti-apoptotic proteins that control MOMP. MLN-9708 treatment induces the release of Cytc, Smac, OMI from mitochondria and decreases the protein levels of XIAP. MLN-9708 inhibits the invasion ability of MG-63 and Saos-2 cells and decreases both the expression and secretion levels of MMP2/9. MLN-9708; 12 nM shows inhibitory activity against C-L and T-L proteasome activities. Treatment of H929 and MM.1S MM cells with MLN-9708 triggers a marked increase in proteolytic cleavage of poly(ADP) ribose polymerase (PARP), a signature event during apoptosis. MLN-9708 induces cleavage of caspase-3, an upstream activator of PARP. MLN-9708 induces eIf2-α kinase activity and protein levels of Bip and CHOP/GADD153. MLN-9708 blocks BMSCs-induced MM cell proliferation, inhibits in vitro capillary tubule formation, and target NF-κB.
MLN-9708, 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 MLN-9708-treated mice show normal levels of creatinine, hemoglobin, and bilirubin. MLN-9708 dramatically increases the number of cleaved-caspase-3 positive cells of the xenograft mode.
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