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.
Chemical Formula: C20H23BCl2N2O9
Exact Mass: 516.08737
Molecular Weight: 517.12162
Elemental Analysis: C, 46.45; H, 4.48; B, 2.09; Cl, 13.71; N, 5.42; O, 27.85
Chemical Name: 4-(carboxymethyl)-2-((R)-1-(2-(2,5-dichlorobenzamido)acetamido)-3-methylbutyl)-6-oxo-1,3,2-dioxaborinane-4-carboxylic acid
InChi Code: InChI=1S/C20H23BCl2N2O9/c1-10(2)5-14(21-33-17(29)8-20(34-21,19(31)32)7-16(27)28)25-15(26)9-24-18(30)12-6-11(22)3-4-13(12)23/h3-4,6,10,14H,5,7-9H2,1-2H3,(H,24,30)(H,25,26)(H,27,28)(H,31,32)/t14-,20?/m0/s1
Appearance: White to off-white solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not soluble in water.
Shelf Life: >5 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
MLN9708; 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.
MLN9708; 12 nM shows inhibitory activity against C-L and T-L proteasome activities. Treatment of H929 and MM.1S MM cells with MLN-970 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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