A patent review of MALT1 inhibitors (2013-present)

verfasst von

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.

Organisationseinheit(en)

Zentrum für Biomolekulare Wirkstoffe (BMWZ)
Institut für Organische Chemie

Externe Organisation(en)

Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

Typ

Übersichtsarbeit

Journal

Expert Opinion on Therapeutic Patents

Band

31

Seiten

1079-1096

Anzahl der Seiten

18

ISSN

1354-3776

Publikationsdatum

2021

Publikationsstatus

Veröffentlicht

Peer-reviewed

Ja

ASJC Scopus Sachgebiete

Pharmakologie, Wirkstoffforschung

Ziele für nachhaltige Entwicklung

SDG 3 – Gute Gesundheit und Wohlergehen

Elektronische Version(en)

https://doi.org/10.1080/13543776.2021.1951703 (Zugang: Geschlossen)