Molecular Weight(MW): 361.03
MLN2238 inhibits the chymotrypsin-like proteolytic (β5) site of the 20S proteasome with IC50 and Ki of 3.4 nM and 0.93 nM in cell-free assays, respectively, also inhibits the caspase-like (β1) and trypsin-like (β2) proteolytic sites, with IC50 of 31 and 3500 nM. Phase 3.
Cited by 7 Publications
4 Customer Reviews
Primary myoblasts from patient 2 harboring a homozygous Arg555Trp DYSF mutation that were treated with the indicated amounts of MLN2238 for 24 hours.
Sci Transl Med 2014 6(250), 250ra112. Ixazomib (MLN2238) purchased from Selleck.
Other proteasome inhibitors that trigger Mcl-1128-350 generation and c-Jun upregulation. MM.1S cells were treated with carfilzomib (Carf), ixazomib (Ixaz), MG-132 (MG), or left untreated. After 24 h, total cell lysate was immunoblotted with Mcl-1, c-Jun and Tubulin.
Cancer Lett 2014 343(2), 286-94. Ixazomib (MLN2238) purchased from Selleck.
Starved WT keratinocytes were treated without (lane 1) or with high calcium (lanes 2-5) in presence of indicated amount of proteasome inhibitor MLN2238 (lane 2-4) for 12 hrs as indicated. Cells were then subjected to immunoblotting analyses using anti-Ctip2 antibody. β-Actin, loading control. All experiments were performed in triplicates.
J Cell Sci 2012 125(Pt 23), 5733-44. Ixazomib (MLN2238) purchased from Selleck.
Purity & Quality Control
Choose Selective Proteasome Inhibitors
|Description||MLN2238 inhibits the chymotrypsin-like proteolytic (β5) site of the 20S proteasome with IC50 and Ki of 3.4 nM and 0.93 nM in cell-free assays, respectively, also inhibits the caspase-like (β1) and trypsin-like (β2) proteolytic sites, with IC50 of 31 and 3500 nM. Phase 3.|
|Features||A first-in-class proteasome inhibitor that has improved pharmacokinetics (PK), pharmacodynamics(PD), and antitumor activity in preclinical studies.|
At higher concentrations, MLN2238 also inhibits the caspase-like (β1) and trypsin-like (β2) proteolytic sites with IC50 of 31nM and 3.5uM, respectively. MLN2238 inhibits Calu-6 cell with IC50 of 9.7 nM. MLN2238 is a selective, potent, and reversible inhibitor of the proteasome in tumor cells. MLN2238 shows time-dependent reversible proteasome inhibition. Both MLN2238 and Bortezomib shows time-dependent reversible proteasome inhibition; however, the proteasome dissociation half-life for MLN2238 is determined to be ∼6-fold faster than that of Bortezomib (18 and 110 minutes, respectively). MLN2238 dissociates more rapidly from the proteasome than Bortezomib, consistent with faster recovery of proteasome activity observed in the Proteasome-Glo assay. MLN2238 has a greater overall tumor pharmacodynamic effect than Bortezomib as assessed by 20S inhibition. MLN2238 is the biologically active form of MLN9708. 
|In vivo||MLN2238 induces a greater pharmacodynamic response than Bortezomib in xenograft tumors. MLN2238 shows greater maximum and sustained tumor proteasome inhibition compared with Bortezomib in xenograft models. These results confirm that the improved tumor exposure seen with MLN2238 translates into an improved tumor pharmacodynamic response both at the level of and downstream from the proteasome. MLN2238 shows antitumor activity in the CWR22 xenograft model. MLN2238 shows greater tumor pharmacodynamic responses in WSU-DLCL2 xenografts compared with Bortezomib. Similarly, Bortezomib treatment only led to a minor increase in GADD34 levels in WSU-DLCL2 xenograft tumors, whereas MLN2238 strongly induces its expression.  MLN2238 has an improved pharmacodynamic profile and antitumor activity compared with Bortezomib in both OCI-Ly10 and PHTX22L models. |
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||72 mg/mL (199.42 mM)|
|Ethanol||9 mg/mL (24.92 mM)|
|In vivo||Add solvents individually and in order:
5% DMSO+45% PEG 300+ddH2O
* 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.
Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:
Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)
*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).
Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )
* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).
Molecular Weight Calculator
Enter the chemical formula of a compound to calculate its molar mass and elemental composition:
Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2
Instructions to calculate molar mass (molecular weight) of a chemical compound:
To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.
Definitions of molecular mass, molecular weight, molar mass and molar weight:
Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
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.
Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.