1. Metabolic Enzyme/Protease
    Autophagy
  2. Proteasome
    Autophagy

MLN9708 (Synonyms: Ixazomib citrate)

Cat. No.: HY-10452 Purity: 99.87%
Data Sheet SDS Handling Instructions

MLN2238 rapidly hydrolyzes to MLN2238, which is a selective, orally bioavailable, second-generation proteasome inhibitor, inhibits the chymotrypsin-like proteolytic (β5) site of the 20S proteasome with an IC50 value of 3.4 nM (Ki of 0.93 nM), and also inhibits the caspase-like (β1) and trypsin-like (β2) proteolytic sites with IC50 of 31 and 3500 nM, respectively.

For research use only. We do not sell to patients.
MLN9708 Chemical Structure

MLN9708 Chemical Structure

CAS No. : 1239908-20-3

Size Price Stock Quantity
10 mM * 1 mL in DMSO USD 82 In-stock
5 mg USD 72 In-stock
10 mg USD 96 In-stock
50 mg USD 180 In-stock
100 mg USD 300 In-stock
200 mg   Get quote  
500 mg   Get quote  

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Customer Review

  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

MLN2238 rapidly hydrolyzes to MLN2238, which is a selective, orally bioavailable, second-generation proteasome inhibitor, inhibits the chymotrypsin-like proteolytic (β5) site of the 20S proteasome with an IC50 value of 3.4 nM (Ki of 0.93 nM), and also inhibits the caspase-like (β1) and trypsin-like (β2) proteolytic sites with IC50 of 31 and 3500 nM, respectively.

IC50 & Target

IC50: 3.4 nM (20S proteasome β5), 31 nM (20S proteasome β1), 3500 nM (20S proteasome β2)[3]

In Vitro

MLN2238 (0.20-3.20 µM) inhibits the cell growth of both cell lines effectively in a time- and dose-dependent manner. MLN2238 induces cell cycle arrest in MG-63 and Saos-2 cells. MLN2238 induces apoptosis mainly through the caspases pathway and requires the activation of both caspase8 and caspase9. MLN2238 treatment increases the levels of pro-apoptotic proteins and down regulates the anti-apoptotic proteins that control MOMP. MLN2238 treatment induces the release of Cytc, Smac, OMI from mitochondria and decreases the protein levels of XIAP. MLN2238 inhibits the invasion ability of MG-63 and Saos-2 cells and decreases both the expression and secretion levels of MMP2/9[1]. MLN2238 (12 nM) shows inhibitory activity against C-L and T-L proteasome activities. Treatment of H929 and MM.1S MM cells with MLN2238 triggers a marked increase in proteolytic cleavage of poly(ADP) ribose polymerase (PARP), a signature event during apoptosis. MLN2238 induces cleavage of caspase-3, an upstream activator of PARP. MLN2238 induces eIf2-α kinase activity and protein levels of Bip and CHOP/GADD153. MLN2238 blocks BMSCs-induced MM cell proliferation, inhibits in vitro capillary tubule formation, and target NF-κB[2].

In Vivo

MLN2238 (11 mg/kg) significantly inhibits MM tumor growth and prolongs survival in the human plasmacytoma MM.1S xenograft mouse model. The blood chemistry profiles of MLN2238-treated mice show normal levels of creatinine, hemoglobin, and bilirubin. MLN2238 dramatically increases the number of cleaved-caspase-3 positive cells of the xenograft model[2].

Clinical Trial
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References
Preparing Stock Solutions
Concentration Volume Mass 1 mg 5 mg 10 mg
1 mM 1.9338 mL 9.6689 mL 19.3379 mL
5 mM 0.3868 mL 1.9338 mL 3.8676 mL
10 mM 0.1934 mL 0.9669 mL 1.9338 mL
Please refer to the solubility information to select the appropriate solvent.
Cell Assay
[1]

MLN2238 is dissolved in DMSO.

Cell viability is assessed using the MTT assay. Cells are trypsinized and seeded in 96-well plate at 5000 cells per well. Cells are treated with MLN2238 or DMSO in basal medium at the indicated doses and times. Cell viability is determined relative to control cells treated with vehicle alone. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[2]

mLN2238 is dissolved in 5% 2-hydroxypropyl-β- cyclodextrin at 2 mg/mL concentration. The human plasmacytoma xenograft tumor model is used in the assay. CB-17 SCID mice (n=21) are subcutaneously inoculated with 5.0×106 MM.1S cells in 100 µL serum-free RPMI-1640 medium, and randomized to treatment groups when tumors reach 250-300 mm3. Mice are treated with vehicle, bortezomib (1 mg/kg; i.v) or mLN2238 (11 mg/kg; i.v) twice weekly for 3 weeks. Animals are euthanized when their tumors reach 2 cm3. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

517.12

Formula

C₂₀H₂₃BCl₂N₂O₉

CAS No.

1239908-20-3

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

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

10 mM in DMSO

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

Purity: 99.87%

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Product Name:
MLN9708
Cat. No.:
HY-10452
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