MLT-827 is a potent and selective inhibitor of MALT1 paracaspase activity with IC50 of 5 nM.
MLT-827 blocks MALT1 substrate cleavage in human CD3+ T lymphocytes stimulated with PMA/Ionomycin in a concentration-dependent manner.
MLT-827 selectively blocks the proteolytic function of MALT1 but does not prevent its scaffolding function, required to engage IκK and JNK signaling.
MLT-827 blocks the pro-survival program triggered by TCR ligation and limits cell expansion.
MLT-827 had only minimal impact on T-cell activation, but profoundly impacted cytokine production, in particular IL-2 and TNF-α.
MLT-827 reduces NF-κB transcriptional activation but has no impact on NF-AT or AP1.
