mepazine

Mepazine (also known as pecazine) is a phenothiazine derivative that was historically developed and marketed in the 1950s as an antipsychotic and tranquilizer under the brand name Pacatal. Although its clinical use in psychiatry was largely discontinued due to adverse effects such as agranulocytosis, mepazine has been repurposed in modern biomedical research as a potent and selective small molecule inhibitor of the **Mucosa-Associated Lymphoid Tissue Lymphoma Translocation Protein 1 (MALT1)** protease. MALT1 is a critical signaling component in immune cells, particularly within the CBM (CARMA1-BCL10-MALT1) complex, which mediates NF-κB activation. By allosterically inhibiting MALT1 protease activity, mepazine suppresses the cleavage of regulatory proteins like CYLD and RELB, thereby inhibiting the survival of MALT1-dependent B-cell lymphomas. Recent studies have also explored mepazine's potential in solid tumors, such as non-small cell lung cancer (NSCLC), where it appears to reprogram the tumor microenvironment by promoting M1 macrophage polarization and suppressing the CD73-adenosine axis, potentially overcoming radioresistance.

Brand names

PacatalPaxital

Other names

pecazinemepazine hydrochloride10-[(1-methyl-3-piperidyl)methyl]phenothiazine