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Hamp, I. ; O'Neill, T.J. ; Plettenburg, O. ; Krappmann, D.

A patent review of MALT1 inhibitors (2013-present).

Expert Opin. Ther. Patents 31, 1079-1096 (2021)
DOI PMC
: Postprint online available 07/2022
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.
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Publication type Article: Journal article
Document type Review
Corresponding Author
Keywords Allosteric Inhibition ; Autoimmunity ; Cancer Immunotherapy ; Lymphoma ; Malt1 ; Proteases ; Regulatory T Cells; Nf-kappa-b; T-cell; Paracaspase Malt1; Allosteric Inhibitors; Protease Activity; Targeting Btk; Activation; Cleavage; Ibrutinib; Mechanisms
ISSN (print) / ISBN 1354-3776
e-ISSN 1744-7674
Journal Expert Opinion on Therapeutic Patents
Quellenangaben Volume: 31, Issue: 12, Pages: 1079-1096 Article Number: , Supplement: ,
Publisher Taylor & Francis
Publishing Place 2-4 Park Square, Milton Park, Abingdon Or14 4rn, Oxon, England
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Research Unit Signaling and Translation (SAT)
Institute of Medicinal Chemistry (IMC)
Grants Deutsche Forschungsgemeinschaft