TY  - JOUR
AB  - INTRODUCTION: MALT1 paracaspase acts as molecular scaffold and a proteolytic enzyme in immune cells. MALT1 has emerged as a promising drug target for cancer therapy, and especially for targeting MALT1 in aggressive lymphomas. Drug discovery programs yielded potent and selective MALT1 protease inhibitors. First-in-class MALT1 inhibitors have been moved to early clinical trials to evaluate safety and efficacy. AREAS COVERED: This review will provide an update regarding the mode of action, the chemical space and therapeutic use of MALT1 inhibitors based on recent patents and the scientific literature (05/2021-12/2024). EXPERT OPINION: Allosteric inhibition is 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.
AU  - Brvar, M.
AU  - O'Neill, T.J.
AU  - Plettenburg, O.
AU  - Krappmann, D.
C1  - 74037
C2  - 57300
CY  - 2-4 Park Square, Milton Park, Abingdon Or14 4rn, Oxon, England
SP  - 639-656 
TI  - An updated patent review of MALT1 inhibitors (2021-present).
JO  - Expert Opin. Ther. Patents
VL  - 35
IS  - 6
PB  - Taylor & Francis Ltd
PY  - 2025
SN  - 1354-3776
ER  - 

TY  - JOUR
AB  - INTRODUCTION: MALT1 is the only human paracaspase, a protease with unique cleavage activity and substrate specificity. As a key regulator of immune responses, MALT1 has attracted attention as an immune modulatory target for the treatment of autoimmune/inflammatory diseases. Further, chronic MALT1 protease activation drives survival of lymphomas, suggesting that MALT1 is a suitable drug target in lymphoid malignancies. Recent studies have indicated that MALT1 inhibition impairs immune suppressive function of regulatory T cells in the tumor microenvironment, suggesting that MALT1 inhibitors may boost anti-tumor immunity in the treatment of solid cancers. AREAS COVERED: : This review summarizes the literature on MALT1 patents and applications. We discuss the potential therapeutic uses for MALT1 inhibitors based on patents and scientific literature. EXPERT OPINION: : There has been a steep increase in MALT1 inhibitor patents. Compounds with high selectivity and good bioavailability have been developed. An allosteric binding pocket is the preferred site for potent and selective MALT1 targeting. MALT1 inhibitors have moved to early clinical trials, but toxicological studies indicate that long-term MALT1 inhibition can disrupt immune homeostasis and lead to autoimmunity. Even though this poses risks, preventing immune suppression may favor the use of MALT1 inhibitors in cancer immunotherapies.
AU  - Hamp, I.
AU  - O'Neill, T.J.
AU  - Plettenburg, O.
AU  - Krappmann, D.
C1  - 62428
C2  - 50866
CY  - 2-4 Park Square, Milton Park, Abingdon Or14 4rn, Oxon, England
SP  - 1079-1096
TI  - A patent review of MALT1 inhibitors (2013-present).
JO  - Expert Opin. Ther. Patents
VL  - 31
IS  - 12
PB  - Taylor & Francis Ltd
PY  - 2021
SN  - 1354-3776
ER  -