Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) acts both as an adapter and an enzyme, which is related to the activation of NF-κB signaling and the negative feedback loop for the signaling. It is reported that NF-κB is chronically activated in the affected tissues of autoimmune diseases and induces inflammatory cytokines and chemokines excessively. Therefore, MALT1 is a potential therapeutic target for autoimmune diseases and lymphomas. We have discovered a novel series of MALT1 inhibitors from a weak hit compound. Exploration of SAR regarding its amide moiety led to the identification of benzenesulfonylguanidine derivatives which showed good potency and metabolic stability. One of the derivatives exhibited good oral bioavailability and in vivo anti-psoriatic activity.

Discovery of benzenesulfonylguanidines as a novel class of allosteric MALT1 inhibitors with in vivo activity for psoriasis

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.