In this study, we describe the identification of M1i-124 and the derivative M1i-124d1, potentially first-in-class BCL10-MALT1 small-molecule PPI inhibitors that show efficacy in inhibiting both MALT1 protease and scaffolding functions and in selectively suppressing the growth and survival of MALT1-dependent ABC-DLBCL cells. This evidence concerns the gene MALT1 and diffuse large B-cell lymphoma.