MLT-748 is a potent, selective and allosteric inhibitor of MALT1, binds MALT1 in the allosteric Trp580 pocket, with an IC50 of 5 nM[1].
MLT-748 reversibly binds to human mutant MALT1(329-728)-W580S (Kd, 13 nM) with affinity similar to that of the wild type MALT1(329-728) (Kd, 42 nM)[1].MLT-748 (0-2 μM) stabilizes cellular MALT1-W580S, with an EC50 of 69 nM[1].MLT-748 (2 µM, 24 hours) increases the phosphorylation of p65 and IκBα in MALT1mut/mut patient immortalized B cells[1].
[1]. Quancard J, et al. An allosteric MALT1 inhibitor is a molecular corrector rescuing function in an immunodeficient patient. Nat Chem Biol. 2019 Mar;15(3):304-313.