MALT1 Inhibitor I, MI-2

Cell permeable: yes

Primary Target
MALT1

Reversible: no

Toxicity: Standard Handling (A)

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.

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

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.

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