Cat. No.: HY-10453

Ixazomib

(Synonyms: MLN2238)

23 Cited Publications

Customer Review

Based on 23 publication(s) in Google Scholar

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 (K_i of 0.93 nM).

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

Purity: 99.30%
CAS No.: 1072833-77-2
Formula: C₁₄H₁₉BCl₂N₂O₄
Molecular Weight:361.03

Storage:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month

Ixazomib Chemical Structure

CAS No.: 1072833-77-2

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Use of MCE Products

Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biological Activity
- Description
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
- Clinical Trial
Chemical Information
Publications (23)
Solvent & Solubility
- In Vitro
- In Vivo
Protocol
Purity & Documentation
References
Help & FAQs
Bioz

Biological Activity

Description

IC₅₀ & Target

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

Cellular Effect

Cell Line	Type	Value	Description	References
ARH-77	IC₅₀	65.5 nM Compound: MLN2238	Cytotoxicity against human ARH77 cells assessed as reduction in cell viability after 72 hrs by CellTiter 96 aqueous one solution assay Cytotoxicity against human ARH77 cells assessed as reduction in cell viability after 72 hrs by CellTiter 96 aqueous one solution assay	[PMID: 29934218]
BT-549	IC₅₀	227.3 nM Compound: Ixazomib	Cytotoxicity against human BT-549 cells assessed as inhibition of cell growth incubated for 72 hrs by MTT assay Cytotoxicity against human BT-549 cells assessed as inhibition of cell growth incubated for 72 hrs by MTT assay	[PMID: 38039793]
Calu-6	IC₅₀	9 nM Compound: MLN2238	Inhibition of 26S proteasome beta5 subunit in human Calu6 cells using Suc-LLVY-aminoluciferin as substrate after 1hr by luminescence assay Inhibition of 26S proteasome beta5 subunit in human Calu6 cells using Suc-LLVY-aminoluciferin as substrate after 1hr by luminescence assay	10.1039/C2MD20060K
HEK293	IC₅₀	6.2 nM Compound: MLN2238	Inhibition of NFkappaB in HEK293 cells incubated for 1 hr prior to TNF-alpha challenge measured after 3 hrs by luciferase reporter gene assay relative to control Inhibition of NFkappaB in HEK293 cells incubated for 1 hr prior to TNF-alpha challenge measured after 3 hrs by luciferase reporter gene assay relative to control	10.1039/C2MD20060K
HeLa	GI₅₀	181.8 μM Compound: MLN 2238	Cytotoxicity in human HeLa cells assessed as reduction in cell viability incubated for 24 hrs by MTT assay Cytotoxicity in human HeLa cells assessed as reduction in cell viability incubated for 24 hrs by MTT assay	[PMID: 32031798]
HepG2	GI₅₀	>200 μM Compound: MLN 2238	Cytotoxicity in human HepG2 cells assessed as reduction in cell viability incubated for 24 hrs by MTT assay Cytotoxicity in human HepG2 cells assessed as reduction in cell viability incubated for 24 hrs by MTT assay	[PMID: 32031798]
MCF7	IC₅₀	135.2 nM Compound: Ixazomib	Cytotoxicity against human MCF7 cells assessed as inhibition of cell growth incubated for 72 hrs by MTT assay Cytotoxicity against human MCF7 cells assessed as inhibition of cell growth incubated for 72 hrs by MTT assay	[PMID: 38039793]
MDA-MB-231	IC₅₀	42.6 nM Compound: Ixazomib	Cytotoxicity against human MDA-MB-231 cells assessed as inhibition of cell growth incubated for 72 hrs by MTT assay Cytotoxicity against human MDA-MB-231 cells assessed as inhibition of cell growth incubated for 72 hrs by MTT assay	[PMID: 38039793]
RPMI-8226	IC₅₀	55.32 nM Compound: MLN2238	Cytotoxicity against human RPMI8226 cells assessed as reduction in cell viability after 72 hrs by CellTiter 96 aqueous one solution assay Cytotoxicity against human RPMI8226 cells assessed as reduction in cell viability after 72 hrs by CellTiter 96 aqueous one solution assay	[PMID: 29934218]
RPMI-8226	IC₅₀	7.4 nM Compound: 18a	Cytotoxicity against human RPMI-8226 cells assessed as inhibition of cell proliferation incubated for 72 hrs by Cell Titer-Glo luminescence assay Cytotoxicity against human RPMI-8226 cells assessed as inhibition of cell proliferation incubated for 72 hrs by Cell Titer-Glo luminescence assay	[PMID: 36806958]
U-266	IC₅₀	52.15 nM Compound: MLN2238	Cytotoxicity against human U266B1 cells assessed as reduction in cell viability after 72 hrs by CellTiter 96 aqueous one solution assay Cytotoxicity against human U266B1 cells assessed as reduction in cell viability after 72 hrs by CellTiter 96 aqueous one solution assay	[PMID: 29934218]

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 (K_i 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].

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

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 (HY-10227) 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 (t_1/2) for Ixazomib (MLN2238) is determined to be 18 minutes^[1].

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

Clinical Trial

NCT Number	Sponsor	Condition	Start Date	Phase A549
NCT01329991	Plexxikon\|		2011-05	PHASE1

Chemical Information

CAS No. 1072833-77-2
Appearance Solid
Molecular Weight 361.03
Formula C₁₄H₁₉BCl₂N₂O₄
Color White to off-white
SMILES

OB([C@@H](NC(CNC(C1=CC(Cl)=CC=C1Cl)=O)=O)CC(C)C)O
Synonyms

MLN2238
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

Publications (23)

All Cell Proliferation/Viability AssayWBIn Vivo Efficacy Study

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Journal Impact Factor

Blood

IDH2 inhibition enhances proteasome inhibitor responsiveness in hematological malignancies. [Abstract]

2019 Jan 10;133(2):156-167. PMID: 30455381
Cell Discov

Suppressing protein damage response to overcome multidrug resistance in cancer therapy. [Abstract]

2025 Sep 30;11(1):80. PMID: 41027888
Cell Rep Med

CAN-Scan: A multi-omic phenotype-driven precision oncology platform identifies prognostic biomarkers of therapy response for colorectal cancer. [Abstract]

2025 Apr 2:102053. PMID: 40187357
Free Radic Biol Med

Targeting ABCB6 with nitidine chloride inhibits PI3K/AKT signaling pathway to promote ferroptosis in multiple myeloma. [Abstract]

2023 Jul:203:86-101. PMID: 37044150

Ixazomib purchased from MedChemExpress. Usage Cited in: Free Radic Biol Med. 2023 Jul:203:86-101. [Abstract]

The inhibitory effects of NC in combination with Bortezomib, Lenalidomide, Carfilzomib and Lxazomib (10 nM) in U266 , 8226, SP2/0 and 8226BTZR cells.
Amyloid

Cell assay for the identification of amyloid inhibitors in systemic AA amyloidosis. [Abstract]

2019 Mar;26(1):24-33. PMID: 30739503
Elife

Renal medullary carcinomas depend upon SMARCB1 loss and are sensitive to proteasome inhibition. [Abstract]

2019 Mar 12:8:e44161. PMID: 30860482

Ixazomib purchased from MedChemExpress. Usage Cited in: Elife. 2019 Mar 12:8:e44161. [Abstract]

G401 xenograft tumor growth over time by individual mouse shows that treatment effects from Lxazomib (MLN2238 ;7 mg/kg IV twice a week for 4 weeks) can be seen as early as 8 days from treatment initiation as compared to vehicle control. Over 26 days, tumor volumes were significantly decreased in MLN2238 treated mice.

Ixazomib purchased from MedChemExpress. Usage Cited in: Elife. 2019 Mar 12:8:e44161. [Abstract]

Kaplan-Meier curves from mice with G401 xenograft tumors treated with either vehicle or Lxazomib (MLN2238 ;7 mg/kg IV twice a week for 4 weeks) over 61 days.
Antimicrob Agents Chemother

Inhibitors of the 20S proteasome β5 subunit as potent and selective agents against Trichomonas vaginalis. [Abstract]

2025 Dec 10;69(12):e0089325. PMID: 41218108
iScience

Identification of a drug-response gene in multiple myeloma through longitudinal single-cell transcriptome sequencing. [Abstract]

2022 Jul 19;25(8):104781. PMID: 35992084

Ixazomib purchased from MedChemExpress. Usage Cited in: iScience. 2022 Jul 19;25(8):104781. [Abstract]

Dose-response curves for KMS-34 cells expressing PELI2, ELF3, or EREG in the presence of Ixazomib (Ixa; 0-2.5 nM; 48 h).
Transl Oncol

poly(I:C) synergizes with proteasome inhibitors to induce apoptosis in cervical cancer cells. [Abstract]

2022 Apr;18:101362. PMID: 35151092
J Biol Chem

Andrographolide targets syndecan4 to impair its interaction with syntenin and inhibits the biogenesis of small extracellular vesicles. [Abstract]

2026 Jan 20:111182. PMID: 41570990
Sci Rep

Proteomic profiling reveals that ESR1 mutations enhance cyclin-dependent kinase signaling. [Abstract]

2024 Mar 22;14(1):6873. PMID: 38519482
J Biol Chem

Diarylheptanoid 35d overcomes EGFR TKI resistance by inducing hsp70-mediated lysosomal degradation of EGFR in EGFR-mutant lung adenocarcinoma. [Abstract]

2023 Jun;299(6):104814. PMID: 37178919

Ixazomib purchased from MedChemExpress. Usage Cited in: J Biol Chem. 2023 Jun;299(6):104814. [Abstract]

Western blot showing EGFR expression in GR6 and GR10 cells treated with 35d (2 μM) and lysosome inhibitors hydroxychloroquine (HCQ), bafilomycinA (bafA) and proteasome inhibitors MG132, Ixazomib (ixa; 0.2, 0.5 μM) at the indicated concentrations for 24 h.
J Pharmacol Exp Ther

Ixazomib Induces Apoptosis and Suppresses Proliferation in Esophageal Squamous Cell Carcinoma through Activation of the c-Myc/NOXA Pathway. [Abstract]

2022 Jan;380(1):15-25. PMID: 34740946
Cell Signal

Identification of a new micropeptide altKLF4 derived from KLF4 that influences myeloma chemotherapeutic sensitivity. [Abstract]

2025 Mar 25:111767. PMID: 40147548
Cell Biochem Funct

Simultaneous proteasome and autophagy inhibition synergistically enhances cytotoxicity of doxorubicin in breast cancer cells. [Abstract]

2022 Jun;40(4):403-416. PMID: 35485606
Biochem Biophys Res Commun

Ixazomib inhibits myeloma cell proliferation by targeting UBE2K. [Abstract]

2021 Apr 16:549:1-7. PMID: 33647537
bioRxiv

2026 Mar 26.
Charles University

2026.
bioRxiv

2024 Jul 25.
bioRxiv

2024 July 19.
bioRxiv

2024 June 12.
University of Pardubice

2023 May 5.
Oncotarget

MEK is a promising target in the basal subtype of bladder cancer. [Abstract]

2020 Nov 3;11(44):3921-3932. PMID: 33216841

Solvent & Solubility

In Vitro:

DMSO : 62.5 mg/mL (173.12 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

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. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.

Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Molarity Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Concentration Concentration

Volume Volume

Molecular Weight Molecular Weight

Dilution Calculator

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

Concentration _(start) Concentration _(start)

Volume _(start) Volume _(start)

Concentration _(final) Concentration _(final)

Volume _(final) Volume _(final)

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

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

Solubility: ≥ 2.08 mg/mL (5.76 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

Protocol 2

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

Solubility: ≥ 2.08 mg/mL (5.76 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil

Solubility: ≥ 2.08 mg/mL (5.76 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
Saline +

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Working solution concentration: 0.22 mg/mL

Protocol

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].

MedChemExpress (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 (AUC_0-48h of 704 and 1,070 h•ng/mL for 0.2 and 0.3 mg/kg doses, respectively) compared with Bortezomib (AUC_0-48h of 206 h•ng/mL), confirming that Ixazomib (MLN2238) also has improved plasma exposure compared with Bortezomib in rodents.

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

Purity & Documentation

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (277 KB)
SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Portuguese - PT (393 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

References

[1]. Kupperman E, et al. Evaluation of the proteasome inhibitor MLN9708 in preclinical models of human cancer. Cancer Res. 2010 Mar 1;70(5):1970-80. [Content Brief]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	2.7699 mL	13.8493 mL	27.6985 mL	69.2463 mL
	5 mM	0.5540 mL	2.7699 mL	5.5397 mL	13.8493 mL
	10 mM	0.2770 mL	1.3849 mL	2.7699 mL	6.9246 mL
	15 mM	0.1847 mL	0.9233 mL	1.8466 mL	4.6164 mL
	20 mM	0.1385 mL	0.6925 mL	1.3849 mL	3.4623 mL
	25 mM	0.1108 mL	0.5540 mL	1.1079 mL	2.7699 mL
	30 mM	0.0923 mL	0.4616 mL	0.9233 mL	2.3082 mL
	40 mM	0.0692 mL	0.3462 mL	0.6925 mL	1.7312 mL
	50 mM	0.0554 mL	0.2770 mL	0.5540 mL	1.3849 mL
	60 mM	0.0462 mL	0.2308 mL	0.4616 mL	1.1541 mL
	80 mM	0.0346 mL	0.1731 mL	0.3462 mL	0.8656 mL
	100 mM	0.0277 mL	0.1385 mL	0.2770 mL	0.6925 mL

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Ixazomib

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Publications Citing Use of MedChemExpress (MCE) Ixazomib

Biological Activity

Chemical Information

Publications (23)

Solvent & Solubility

Protocol

Purity & Documentation

References

Help & FAQs

Complete Stock Solution Preparation Table

Ixazomib Related Classifications

Cat. No.: HY-10453