JNJ-64041575

JNJ-64041575 is an orally bioavailable prodrug of JNJ-63549109, a potent and selective small molecule inhibitor of the Mucosa-Associated Lymphoid Tissue Lymphoma Translocation Protein 1 (MALT1) protease. Developed by Janssen, JNJ-64041575 is primarily being investigated for the treatment of B-cell malignancies, including diffuse large B-cell lymphoma (DLBCL). MALT1 is a paracaspase that plays a critical role in the CBM (CARMA1-BCL10-MALT1) complex, which is essential for NF-κB signaling following B-cell receptor (BCR) activation. In many B-cell lymphomas, constitutive MALT1 protease activity drives aberrant NF-κB signaling, promoting cell survival and proliferation. By inhibiting MALT1, JNJ-64041575 (via its active metabolite) disrupts these oncogenic signaling pathways, leading to growth arrest and apoptosis in sensitive tumor cells.