Ixazomib Citrate (MLN9708)
For research use only.
CAS No. 1201902-80-8
Ixazomib Citrate (MLN9708) immediately hydrolyzed to Ixazomib (MLN2238), the biologically active form, on exposure to aqueous solutions or plasma. Ixazomib (MLN2238) inhibits the chymotrypsin-like proteolytic (β5) site of the 20S proteasome with IC50/Ki of 3.4 nM/0.93 nM in cell-free assays, less potent to β1 and little activity to β2. Ixazomib (MLN2238) induces autophagy. Phase 3.
Selleck's Ixazomib Citrate (MLN9708) has been cited by 25 publications
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|Description||Ixazomib Citrate (MLN9708) immediately hydrolyzed to Ixazomib (MLN2238), the biologically active form, on exposure to aqueous solutions or plasma. Ixazomib (MLN2238) inhibits the chymotrypsin-like proteolytic (β5) site of the 20S proteasome with IC50/Ki of 3.4 nM/0.93 nM in cell-free assays, less potent to β1 and little activity to β2. Ixazomib (MLN2238) induces autophagy. Phase 3.|
|Features||The 1st oral proteasome inhibitor in early stage clinical trials for Multiple Myeloma.|
MLN9708 is a selective, orally bioavailable, second-generation proteasome inhibitor. MLN9708 has a shorter proteasome dissociation half-life and improved pharmacokinetics, pharmacodynamics, and antitumor activity compared with bortezomib, which we believe plays an important role in its improved tissue distribution. MLN9708 has a larger blood volume distribution at steady state, and analysis of 20S proteasome inhibition and markers of the unfolded protein response confirms that MLN9708 has greater pharmacodynamic effects in tissues than bortezomib. MLN9708 is a second-generation small-molecule proteasome inhibitor being developed for the treatment of a broad range of human malignancies.  Upon exposure to aqueous solutions or plasma, MLN9708 rapidly hydrolyzes to its biologically active form MLN2238.  MLN2238 is the biologically active form of MLN9708. 
|In vivo||MLN9708 shows superior antitumor activity in both solid tumor and hematologic preclinical xenograft models when administered via multiple dosing routes and regimens.  Recent preclinical pharmacology studies shows that MLN9708 has a shorter proteasome dissociation half-life than bortezomib, as well as improved pharmacokinetics, pharmacodynamics, and antitumor activity in xenograft models  MLN9708 has shown antitumor efficacy in a wide range of tumor xenografts. |
Kinase assay:Calu-6 cells are cultured in MEM containing 10% fetal bovine serum and 1% penicillin/streptomycin and plated 1 day before the start of the experiment at 1 × 104 cells per well in a 384-well plate. Proteasome activity is assessed by monitoring hydrolysis of the chymotrypsin-like substrate Suc-LLVY-aminoluciferin in the presence of luciferase using the Proteasome-Glo assay reagents according to the manufacturer's instructions. Luminescence is measured using a LEADseeker instrument.
|In vitro||DMSO||100 mg/mL (193.37 mM)|
|In vivo||Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
0.5% hydroxyethyl cellulose
For best results, use promptly after mixing.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
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|Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)|
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Clinical Trial Information
|NCT Number||Recruitment||interventions||Conditions||Sponsor/Collaborators||Start Date||Phases|
|NCT03422874||Withdrawn||Drug: MLN9708|Drug: Nelfinavir||Neoplasms|Lymphoma||Dartmouth-Hitchcock Medical Center||August 2016||Phase 1|
|NCT02582359||Recruiting||Drug: MLN9708|Drug: Cytarabine|Drug: Daunorubicin||Acute Myeloid Leukemia||Massachusetts General Hospital|Millennium Pharmaceuticals Inc.||January 2016||Phase 1|
|NCT02250300||Completed||Drug: MLN9708||Allogeneic Hematopoietic Stem Cell Transplantation||Mehdi Hamadani|Medical College of Wisconsin||November 19 2014||Phase 1|Phase 2|
|NCT01936532||Active not recruiting||Drug: MLN9708|Drug: Lenalidomide|Drug: Dexamethasone||Newly Diagnosed Multiple Myeloma||Nantes University Hospital||November 12 2014||Phase 2|
|NCT02168101||Completed||Drug: MLN9708||Multiple Myeloma||SCRI Development Innovations LLC|Millennium Pharmaceuticals Inc.||September 2014||Phase 2|
Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.
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