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Updated: Jan 11, 2026
Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
Published on: January 7, 2019
Targeting paracaspase1 (MALT1) for cancer therapy: Updated progress and study on structure-activity relationships
Yinglong Li1, Yanyun Hong1, Jianye Zhang1
1Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, 605 Fenglin Road, Nanchang, Jiangxi, 330013, China.
Abstract:
As a paracaspase, mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) plays a crucial role in the NF-κB signaling pathway. It typically exerts its function by forming a ternary complex with CARMA and BCL. The structure of MALT1 endows it with dual roles as a protease and a scaffold protein, both of which are of great significance for the regulation of the signaling pathway. Activated B-cell like diffuse large B-cell lymphoma (ABC-DLBCL) is characterized by high complication rates and mortality. Studies have demonstrated that its pathogenesis relies on the NF-κB pathway mediated by the CBM complex (CARMA-Bcl10-MALT1 complex). As the only human cysteine-aspartic acid protease (caspase-like protease) in the CBM complex, MALT1 has thus become a key target, making the research on MALT1 inhibitors of substantial importance. This review provides an overview of the research progress and structure-activity relationships (SARs) of MALT1 inhibitors, including covalent inhibitors, allosteric inhibitors, PROTACs (Proteolysis-Targeting Chimeras), and activity-based probes. Additionally, it discusses the future opportunities and challenges in this field, aiming to provide insights for the future development of MALT1-targeted drugs.
Insights
Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is vital for NF-κB signaling and implicated in ABC-DLBCL. This review details MALT1 inhibitors, including covalent, allosteric, PROTACs, and probes, highlighting future drug development opportunities.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a paracaspase crucial for NF-κB signaling via the CBM complex.
- MALT1's dual protease and scaffold functions are key regulators of this pathway.
- Activated B-cell like diffuse large B-cell lymphoma (ABC-DLBCL) pathogenesis is NF-κB dependent, making MALT1 a critical therapeutic target.
Purpose of the Study:
- To review the current research progress on MALT1 inhibitors.
- To analyze the structure-activity relationships (SARs) of various MALT1 inhibitor classes.
- To discuss future challenges and opportunities in MALT1-targeted drug development.
Main Methods:
- Literature review of MALT1 inhibitors.
- Analysis of structure-activity relationships (SARs).
- Discussion of covalent inhibitors, allosteric inhibitors, PROTACs, and activity-based probes.
Main Results:
- Overview of MALT1 inhibitor research progress.
- Detailed SAR analysis for different inhibitor types.
- Identification of key research areas and potential therapeutic strategies.
Conclusions:
- MALT1 is a significant therapeutic target for ABC-DLBCL due to its role in NF-κB signaling.
- Various inhibitor strategies, including covalent, allosteric, PROTACs, and probes, show promise.
- Further research into MALT1 inhibitors is essential for developing effective treatments for ABC-DLBCL.
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