MI 2 is an inhibitor of the paracaspase MALT1 with an IC50 value of 5.84 μM in a fluorescence assay.1 It inhibits the growth of MALT1-dependent activated B cell-like diffuse large B cell lymphoma (ABC-DLBCL) cell lines (GI50s = 0.2, 0.5, 0.4, and 0.4 μM for HBL-1, TMD8, OCI-Ly3, and OCI-Ly10 cells, respectively). MI 2 inhibits cleavage of the MALT1 target protein CYLD in a dose-dependent manner in HBL-1 cells but does not inhibit caspase-3, caspase-8, and caspase-9, which are structurally similar to MALT1. MI 2 (25 mg/kg, i.v.) reduces tumor size in TMD8 and HBL-1 mouse xenograft models.
1.Fontan, L., Yang, C., Kabaleeswaran, V., et al.MALT1 small molecule inhibitors specifically suppress ABC-DLBCL in vitro and in vivoCancer Cell.22(6)812-824(2012)