MLN9708

Cell lines

MM.1S (Dexamethasone sensitive) cells

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 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.

Reaction Conditions

100 nM, 3 hours for CT-L proteasome inhibition 100 nm, 3 hours for C-L proteasome inhibition 10 μM, 3 hours for T-L proteasome inhibition

Applications

MLN9708 significantly inhibited CT-L proteasome activity with an IC50 at 5 nM. Higher concentrations of MLN9708 showed inhibitory activity against C-L and T-L proteasome activities.

Animal models

Female CB17-SCID mice bearing WSU-DLCL2 xenografts

Dosage form

Intravenous injection, 14 mg/kg, twice weekly or subcutaneous injection, 4 mg/kg, once daily

Applications

Both intermittent and continuous MLN2238 dosing regimens showed strong antitumor activity (T/C = 0.44 and 0.29 for 14 mg/kg i.v. and 4 mg/kg s.c., respectively) and generated a greater apoptotic response in tumor tissue asmeasured by levels of cleaved caspase-3.

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.

References:

[1] Chauhan D, Tian Z, Zhou B, et al. In vitro and in vivo selective antitumor activity of a novel orally bioavailable proteasome inhibitor MLN9708 against multiple myeloma cells. Clinical Cancer Research, 2011, 17(16): 5311-5321.

[2] Kupperman E, Lee E C, Cao Y, et al. Evaluation of the proteasome inhibitor MLN9708 in preclinical models of human cancer. Cancer research, 2010, 70(5): 1970-1980.