MI-2 binds directly to MALT1 and irreversibly suppresses protease function. MI-2 decreases NF-κB activity induced by MALT1. MI-2 inhibits cell proliferation and MALT1-mediated cleavage activity. MI-2 concentrates within human ABC-DLBCL cells and irreversibly inhibited cleavage of MALT1 substrates. MI-2 displayes selective activity against ABC-DLBCL cell lines in vitro and xenotransplanted ABC-DLBCL tumors in vivo.
||MLL-AF9 and E2A-HLF transduced murine BMC
||Plating the MLL-AF9 and E2A-HLF transduced murine BMC in 12-well plates at the concentration of 5×103 cells/mL with 1 mL methylcellulose medium M3234 containing 20% IMDM medium, 1% penicillin/streptomycin, IL-3 and 0.25% DMSO or compounds.After 6 days staining colonies with 100 μL iodonitrotetrazolium chloride at final concentration of 1 mg/mL, incubating at 37°C for 30 min and counting . To replate for the 2nd round, counting colonies at day 6 without staining and washing cells out by 1×PBS buffer and resuspending in IMDM medium which contains 15% FBS, 1% penicillin/streptomycin and IL-3.Plateing 5×103 cells in 12-well plates with 1ml methycellulose medium M3234 containing 20% IMDM medium, 1% penicillin/streptomycin, IL-3 and 0.25% DMSO or compounds. 6 days later staining and counting colonies .
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
|Body Surface Area (m2)
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by
||Animal B Km
|Animal A Km
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
MALT1 small molecule inhibitors specifically suppress ABC-DLBCL in vitro and in vivo.
Fontan L, et al. Cancer Cell. 2012 Dec 11;22(6):812-24. PMID: 23238016.