MLN2238
MLN2238 (CAS number: 1072833-77-2) is a dipeptidyl boronic acid derivative designed as a reversible inhibitor of the β5 subunit (chymotrypsin-like activity) of the 20S proteasome, with reported IC50 and Ki values of 3.4 nM and 0.93 nM, respectively. At higher concentrations, MLN2238 also targets the proteasome's β1 (caspase-like) and β2 (trypsin-like) subunits. In preclinical studies using xenograft and genetically-engineered models of hematologic malignancies, MLN2238 exhibited potent antitumor activity, promoting apoptosis and suppressing pathways such as NF-κB. MLN2238 has research applications in oncology, particularly against multiple myeloma and lymphoma, including in bortezomib-resistant cell lines.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 361 |
| Cas No. | 1072833-77-2 |
| Formula | C14H19BCl2N2O4 |
| Solubility | insoluble in H2O; ≥103 mg/mL in EtOH with ultrasonic; ≥16.8 mg/mL in DMSO |
| Chemical Name | [(1R)-1-[[(2S,3R)-3-hydroxy-2-[(6-phenylpyridine-2-carbonyl)amino]butanoyl]amino]-3-methylbutyl]boronic acid |
| SDF | Download SDF |
| Canonical SMILES | B(C(CC(C)C)NC(=O)CNC(=O)C1=C(C=CC(=C1)Cl)Cl)(O)O |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Kinase experiment [1]: | |
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Kinase assay |
Calu-6 cells were 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 was 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 was measured using a LEADseeker instrument. |
| Cell experiment [1]: | |
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Cell lines |
Calu-6 cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reaction Conditions |
≤ 10 nM; 1 hr |
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Applications |
MLN2238 inhibited Calu-6 cells with an IC50 value of 9.7 nM. |
| Animal experiment [2]: | |
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Animal models |
DP54-Luc tumor-bearing NOD-SCID mice |
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Dosage form |
11 mg/kg; i.v.; twice weekly for 17 consecutive days |
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Applications |
Both Bortezomib and MLN2238 reduced tumor burden (T/C = 0.48 and 0.22, respectively). |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Kupperman E, Lee EC, Cao Y, et al. Evaluation of the proteasome inhibitor MLN9708 in preclinical models of human cancer. Cancer Research, 2010, 70 (5): 1970-80. [2]. Lee EC, Fitzgerald M, Bannerman B, et al. Antitumor Activity of the Investigational Proteasome Inhibitor MLN9708 in Mouse Models of B-cell and Plasma Cell Malignancies. CLINICAL CANCER RESEARCH, 2011, 17 (23): 7313-7323. |
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| Description | MLN2238 is an inhibitor of the chymotrypsin-like proteolytic (β5) site of the 20S proteasome with IC50 and Ki values of 3.4 nM and 0.93 nM, also inhibitor of the caspase-like (β1) and trypsin-like (β2) proteolytic sites with IC50 values of 31 nM and 3500 nM, respectively. | |||||
| Targets | chymotrypsin-like proteolytic (β5) site of the 20S proteasome | caspase-like (β1) proteolytic sites proteasome | trypsin-like (β2) proteolytic sites proteasome | |||
| IC50 | 3.4 nM (Ki=0.93 nM) | 31 nM | 3500 nM | |||
Quality Control & MSDS
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