MALT1 Inhibitor III, Mepazine Acetate

A cell-permeable phenothiazine that inhibits MALT1, but not caspase-3 or -8, proteolytic activity (IC₅₀ = 0.83 and 0.42 µM, respectively, against full-length or paracaspase domain-containing aa 325-760 MALT1 GST fusion-catalyzed Ac-LRSR-AMC hydrolysis) in a reversible and noncompetitive manner and blocks anti-CD3/CD28-stimulated IL-6 production (20 h) in primary murine CD4⁺ T-cell (by 77%) and human PBMC cultures (by 51 - 89%). Shown to suppress ABC-DLBCL constitutive cellular MALT1 activity (>75% suppression by 10 µM Mepazine; IC₅₀<5 µM in U2932, OCI-Ly10, OCI-Ly3, HBL1, and TMD8 cultures) and RelB cleavage, resulting in effective blockage of NF-κB-dependent IL-6, IL-10, as well as anti-apoptotic Bcl-x_L and FLIP-L expressions. Mepazine exhibits ABC-DLBCL-selective cytotoxicity (≥27% cell death in 4 days by 10 µM Mepazine in HBL-1, OCI-Ly3, OCI-Ly10, TMD8, and U2932 cultures) over GCB-DLBCL (≤26% cell death in 4 days by 20 µM Mepazine in DJAB, Su-DHL-4, and Su-DHL-6 cultures) both in cultures in vitro and in mice (74%, and 0% suppression, respectively, of OCI-Ly10 and Su-DHL-6 tumor expansion on day 22 post cancer transplant; via daily 400 µg/kg i.p.) in vivo.

Cell permeable: yes

Primary Target
MALT1

Reversible: yes

Target IC₅₀: 0.83 and 0.42 &micro

Packaged under inert gas

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

Schlauderer, F., et al. 2013. Angew. Chem. Int. Ed.52, 10384.
Nagel, D., et al. 2012. Cancer Cell.22, 825.

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

Toxicity: Standard Handling (A)