A patent review of MALT1 inhibitors (2013-present)

authored by: Isabel Hamp, Thomas J. O’Neill, Oliver Plettenburg, Daniel Krappmann
Abstract: 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 for 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.
Organisation(s): Centre of Biomolecular Drug Research (BMWZ)
Institute of Organic Chemistry
External Organisation(s): Helmholtz Zentrum München - German Research Center for Environmental Health
Type: Review article
Journal: Expert Opinion on Therapeutic Patents
Volume: 31
Pages: 1079-1096
No. of pages: 18
ISSN: 1354-3776
Publication date: 2021
Publication status: Published
Peer reviewed: Yes
ASJC Scopus subject areas: Pharmacology, Drug Discovery
Sustainable Development Goals: SDG 3 - Good Health and Well-being
Electronic version(s): https://doi.org/10.1080/13543776.2021.1951703 (Access: Closed)