MALT1 Inhibitor I, MI-2

A cell-permeable chloromethyl amide that inhibits MALT1 proteolytic activity (IC₅₀ = 5.84 µM against MALT1 paracaspase domain dimer-catalyzed Ac-LRSR-AMC hydrolysis) in an irreversible manner via covalent interaction, displaying little or no activity against caspase-3, -8, or -9. Due to irreversible binding and effective intracellular accumulation (HBL-1 intracellular [MI-2]_{t = 2 h} = 5 µM; Medium [MI-2]_{t = 0} = 0.2 µM), MI-2 is at least 250-times more effective than Z-VRPR-FMK in blocking constitutive NF-κB activity and c-Rel nuclear translocation in HBL-1 cultures (equal or better blockage by 200 nM MI-2 than by 50 µM Z-VRPR-FMK). Shown to selectively inhibit MALT1-dependent ABC-DLBCL proliferation, but not the MALT1-independent growths of ABC- (HLY-1 and U2932) or GCB-DLBCL (OCI-Ly1 and OCI-Ly7) cells, both in cultures in vitro (GI₅₀ in 48 h = 200, 400, 400, and 500 nM, respectively, against HBL-1, OCI-Ly3, OCI-Ly10, and TMD8) and in mice in vivo (65%,, 61%, and 0% suppression, respectively, of HBL-1, TMD8, and OCI-Ly1 tumor expansion 24 h after 14 daily 25 mg/kg/day i.p. dosages) without any apparent toxicity to mice.

Please note that the molecular weight for this compound is batch-specific due to variable water content. Please refer to the vial label or the certificate of analysis for the batch-specific molecular weight. The molecular weight provided represents the baseline molecular weight without water.

Cell permeable: yes

Primary Target
MALT1

Reversible: no

Packaged under inert gas

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Use only fresh DMSO for reconstitution.

Fontan, L., et al. 2012. Cancer Cell22, 812.

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Toxicity: Standard Handling (A)