Ixazomib (MLN2238)

Catalog No.S2180 Batch:S218003

Print

Technical Data

Formula

C14H19BCl2N2O4
Molecular Weight 361.03 CAS No. 1072833-77-2
Solubility (25°C)* In vitro DMSO 72 mg/mL (199.42 mM)
Ethanol 72 mg/mL (199.42 mM)
Water Insoluble
In vivo (Add solvents to the product individually and in order)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml means slightly soluble or insoluble.
* 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description Ixazomib (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. This compound induces autophagy. Phase 3.
Targets
20S proteasome [1]
(Cell-free assay)		 20S proteasome [1]
(Cell-free assay)
0.93 nM(Ki) 3.4 nM
In vitro At higher concentrations, this compound also inhibits the caspase-like (β1) and trypsin-like (β2) proteolytic sites with IC50 of 31nM and 3.5uM, respectively. It inhibits Calu-6 cell with IC50 of 9.7 nM. MLN2238 is a selective, potent, and reversible inhibitor of the proteasome in tumor cells. This compound shows time-dependent reversible proteasome inhibition. Both this compound and Bortezomib shows time-dependent reversible proteasome inhibition; however, the proteasome dissociation half-life for it is determined to be ∼6-fold faster than that of Bortezomib (18 and 110 minutes, respectively). It dissociates more rapidly from the proteasome than Bortezomib, consistent with faster recovery of proteasome activity observed in the Proteasome-Glo assay. It has a greater overall tumor pharmacodynamic effect than Bortezomib as assessed by 20S inhibition. [1]This compound is the biologically active form of MLN9708. [2]
In vivo MLN2238 induces a greater pharmacodynamic response than Bortezomib in xenograft tumors. This compound shows greater maximum and sustained tumor proteasome inhibition compared with Bortezomib in xenograft models. These results confirm that the improved tumor exposure seen with this agent translates into an improved tumor pharmacodynamic response both at the level of and downstream from the proteasome. It shows antitumor activity in the CWR22 xenograft model. This chemical 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 it strongly induces its expression. [1] This compound has an improved pharmacodynamic profile and antitumor activity compared with Bortezomib in both OCI-Ly10 and PHTX22L models. [2]
Features A first-in-class proteasome inhibitor that has improved pharmacokinetics (PK), pharmacodynamics(PD), and antitumor activity in preclinical studies.

Protocol (from reference)

Kinase Assay:[1]
  • 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.
Cell Assay:[1]
  • Cell lines

    Calu-6 cells

  • Concentrations

    ~10 nM

  • Incubation Time

    1 hour or 30 minutes

  • Method

    Calu-6 cells are cultured in MEM containing 10% FBS 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. For IC50 determinations, cells are treated with varying concentrations of Bortezomib or this compound in DMSO (0.5% final, v/v) for 1 hour at 37 °C. For reversibility experiments, cells are treated with either 1 μM Bortezomib or this chemical for 30 minutes at 37 °C and then washed thrice in medium to remove the Bortezomib or this agent. Cells are incubated for an additional 4 hours at 37 °C, after which the medium is removed and replaced with fresh medium.
Animal Study:[2]
  • Animal Models

    CB-17 SCID mice are subcutaneously inoculated with MM.1S cells

  • Dosages

    11 mg/kg

  • Administration

    Twice weekly for 3 weeks (i.v.)

References

  • https://pubmed.ncbi.nlm.nih.gov/20160034/
  • https://pubmed.ncbi.nlm.nih.gov/21903769/

Customer Product Validation

Primary myoblasts from patient 2 harboring a homozygous Arg555Trp DYSF mutation that were treated with the indicated amounts of MLN2238 for 24 hours.

Data from [ Sci Transl Med , 2014 , 6(250), 250ra112 ]

Other proteasome inhibitors that trigger Mcl-1<sup>128-350</sup> 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.

Data from [ Cancer Lett , 2014 , 343(2), 286-94 ]

Nrf2 bound to ARE sequences was measured by immunoassay in nuclear extracts from K562 cells after treatment with tBHQ, bortezomib and MLN 2238.

Data from [ Hemoglobin , 2014 , 38(3), 188-95 ]

<p>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.</p>

Data from [ J Cell Sci , 2012 , 125(Pt 23), 5733-44 ]

Selleck's Ixazomib (MLN2238) Has Been Cited by 79 Publications

Structural basis for allosteric modulation of M. tuberculosis proteasome core particle [ Nat Commun, 2025, 16(1):3138] PubMed: 40169579
A patient-derived T cell lymphoma biorepository uncovers pathogenetic mechanisms and host-related therapeutic vulnerabilities [ Cell Rep Med, 2025, S2666-3791(25)00102-8] PubMed: 40147445
Enhancing T cell cytotoxicity in multiple myeloma with bispecific αPD-L1 × αCD3 T cell engager-armed T cells and low-dose bortezomib therapy [ Biomed Pharmacother, 2025, 184:117878] PubMed: 39891948
High-Throughput Drug Screening of Clear Cell Ovarian Cancer Organoids Reveals Vulnerability to Proteasome Inhibitors and Dinaciclib and Identifies AGR2 as a Therapeutic Target [ Cancer Res Commun, 2025, 5(6):1018-1033] PubMed: 40459063
Integrated transcriptomics- and structure-based drug repositioning identifies drugs with proteasome inhibitor properties [ Sci Rep, 2024, 14(1):18772] PubMed: 39138277
A combinatorial therapeutic approach to enhance FLT3-ITD AML treatment [ Cell Rep Med, 2023, 10.1016/j.xcrm.2023.101286] PubMed: 37951217
Targeting ITGB4/SOX2-driven lung cancer stem cells using proteasome inhibitors [ iScience, 2023, 26(8):107302] PubMed: 37554452
Targeting ITGB4/SOX2-driven lung cancer stem cells using proteasome inhibitors [ iScience, 2023, 26(8):107302] PubMed: 37554452
Dual inhibition of HSF1 and DYRK2 impedes cancer progression [ Biosci Rep, 2023, 43(1)BSR20222102] PubMed: 36622366
Proteasome inhibition as a therapeutic target for the fungal pathogen Cryptococcus neoformans [ Microbiol Spectr, 2023, 11(5):e0190423] PubMed: 37750732

RETURN POLICY
Selleck Chemical’s Unconditional Return Policy ensures a smooth online shopping experience for our customers. If you are in any way unsatisfied with your purchase, you may return any item(s) within 7 days of receiving it. In the event of product quality issues, either protocol related or product related problems, you may return any item(s) within 365 days from the original purchase date. Please follow the instructions below when returning products.

SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.