1. Metabolic Enzyme/Protease
    Autophagy
  2. Proteasome
    Autophagy
  3. Ixazomib

Ixazomib (Synonyms: MLN2238)

Cat. No.: HY-10453 Purity: 99.24%
Handling Instructions

Ixazomib (MLN2238) is a selective, potent, and reversible proteasome inhibitor, which inhibits the chymotrypsin-like proteolytic (β5) site of the 20S proteasome with an IC50 of 3.4 nM (Ki of 0.93 nM).

For research use only. We do not sell to patients.

Ixazomib Chemical Structure

Ixazomib Chemical Structure

CAS No. : 1072833-77-2

Size Price Stock Quantity
10 mM * 1 mL in DMSO USD 119 In-stock
Estimated Time of Arrival: December 31
5 mg USD 108 In-stock
Estimated Time of Arrival: December 31
10 mg USD 144 In-stock
Estimated Time of Arrival: December 31
25 mg USD 324 In-stock
Estimated Time of Arrival: December 31
50 mg USD 540 In-stock
Estimated Time of Arrival: December 31
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Customer Review

Based on 4 publication(s) in Google Scholar

Other Forms of Ixazomib:

Top Publications Citing Use of Products

    Ixazomib purchased from MCE. Usage Cited in: bioRxiv. 2018 Dec.

    Cell lines are treated with DMSO, bortezomib or MLN2238 for 48 hours. c-MYC protein levels in RPMI8226, a multiple myeloma cell line, decrease following proteasome inhibition by immunoblot.
    • Biological Activity

    • Protocol

    • Purity & Documentation

    • References

    • Customer Review

    Description

    Ixazomib (MLN2238) is a selective, potent, and reversible proteasome inhibitor, which inhibits the chymotrypsin-like proteolytic (β5) site of the 20S proteasome with an IC50 of 3.4 nM (Ki of 0.93 nM).

    IC50 & Target

    IC50: 3.4 nM (20S proteasome)[1]
    Ki: 0.93 nM (20S proteasome)[1]

    In Vitro

    Ixazomib (MLN2238) is an N-capped dipeptidyl leucine boronic acid and preferentially bound to and inhibited the chymotrypsin-like proteolytic (β5) site of the 20S proteasome with an IC50 value of 3.4 nM (Ki of 0.93 nM). At higher concentrations, Ixazomib (MLN2238) also inhibits the caspase-like (β1) and trypsin-like (β2) proteolytic sites (IC50 of 31 and 3,500 nM, respectively). Cell viability studies are performed in a variety of mammalian cell lines to compare the in vitro antiproliferative effects of Ixazomib (MLN2238) with Bortezomib. Studies performed with A375 (lung), H460 (lung), HCT-116 (colon), and HT-29 (colon) cells revealed similar LD50 values for the two compounds, which range from 4 to 58 nM[1].

    In Vivo

    Ixazomib (MLN2238) shows antitumor activity in the CWR22 xenograft model. The antitumor effects of Ixazomib (MLN2238) dosed at 14 mg/kg i.v. or 7 mg/kg i.v. are compared with Bortezomib dosed at 0.8 mg/kg i.v. or 0.4 mg/kg i.v. on a twice weekly regimen. The high dose for both Ixazomib (MLN2238) and Bortezomib shows similar antitumor activity in this model (T/C=0.36 and 0.44, respectively). However, Ixazomib (MLN2238) (7 mg/kg) shows greater efficacy at a 0.5 MTD dose compared with a 0.5 MTD dose of Bortezomib (0.4 mg/kg; T/C=0.49 compared with T/C=0.79, respectively) Ixazomib (MLN2238) shows time-dependent reversible proteasome inhibition; however, the proteasome dissociation half-life (t1/2) for Ixazomib (MLN2238) is determined to be 18 minutes[1].

    Clinical Trial
    Molecular Weight

    361.03

    Formula

    C₁₄H₁₉BCl₂N₂O₄

    CAS No.

    1072833-77-2

    SMILES

    CC(C)C[[email protected]@H](B(O)O)NC(CNC(C1=CC(Cl)=CC=C1Cl)=O)=O

    Shipping

    Room temperature in continental US; may vary elsewhere.

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Solvent & Solubility
    In Vitro: 

    DMSO : ≥ 28 mg/mL (77.56 mM)

    H2O : < 0.1 mg/mL (insoluble)

    *"≥" means soluble, but saturation unknown.

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 2.7699 mL 13.8493 mL 27.6985 mL
    5 mM 0.5540 mL 2.7699 mL 5.5397 mL
    10 mM 0.2770 mL 1.3849 mL 2.7699 mL
    *Please refer to the solubility information to select the appropriate solvent.
    In Vivo:
    • 1.

      Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% saline

      Solubility: ≥ 2.5 mg/mL (6.92 mM); Clear solution

    • 2.

      Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in saline)

      Solubility: 2.5 mg/mL (6.92 mM); Suspended solution; Need ultrasonic

    • 3.

      Add each solvent one by one:  10% DMSO    90% corn oil

      Solubility: ≥ 2.5 mg/mL (6.92 mM); Clear solution

    *All of the co-solvents are provided by MCE.
    References
    Cell Assay
    [1]

    Calu-6 cells are cultured in MEM containing 10% fetal bovine serum and 1% penicillin/streptomycin and plated 1 d before the start of the experiment at 10,000 cells per well in a 384-well plate. For IC50 determinations, cells are treated with varying concentrations of Bortezomib or Ixazomib in DMSO (0.5% final, v/v) for 1 h at 37°C. For reversibility experiments, cells are treated with either 1 μM Bortezomib or Ixazomib (MLN2238) for 30 min at 37°C and then washed thrice in medium to remove the compounds. Cells are incubated for an additional 4 h at 37°C, after which the medium is removed and replaced with fresh medium. 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. Luminescence is measured using a LEADseeker instrument[1].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [1]

    Mice[1]
    Male CB17-SCID mice, approximately 8 to 11 wk of age, are inoculated s.c. with freshly dissected CWR22 tumor fragments (~20 mg) in the right dorsal flank. Mean tumor volume (MTV) is calculated using the following formula: 0.5×(length×width2). When MTV reaches approximately 150 to 200 mm3, animals are randomized into treatment groups (n=10 per group) before dosing. Antitumor activity is determined at the end of the study by calculating the treatment over control (T/C) ratio of their MTVs at the end of the study.
    Rats[1]
    To determine the pharmacokinetic profile of Ixazomib and Bortezomib in a second species, Sprague-Dawley rats are administered a single i.v. dose of Ixazomib (MLN2238) at either 0.3 or 0.2 mg/kg or Bortezomib at 0.2 mg/kg. Both Ixazomib doses provided a greater plasma exposure (AUC0-48h of 704 and 1,070 h•ng/mL for 0.2 and 0.3 mg/kg doses, respectively) compared with Bortezomib (AUC0-48h of 206 h•ng/mL), confirming that Ixazomib (MLN2238) also has improved plasma exposure compared with Bortezomib in rodents.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
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    Keywords:

    IxazomibMLN2238MLN 2238MLN-2238ProteasomeAutophagyInhibitorinhibitorinhibit

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