An updated patent review of MALT1 inhibitors (2021–present)

Allosteric inhibition is the preferred mode of action to inhibit the MALT1 protease. Chemical advances largely focus on improving binding and inhibition in the allosteric site of MALT1. New composition of matter has been generated, but a clinical proof for the safety and efficacy of allosteric MALT1 inhibitors is still pending. We still lack potent and selective competitive or covalent MALT1 inhibitors, indicating the challenges with targeting the active site. Further, MALT1 protein degraders and MALT1 scaffolding inhibitors have been developed, which may have distinct inhibitory profiles compared to allosteric MALT1 protease inhibitors, but more potent and selective compounds are needed to judge the feasibility and usefulness of these approaches.