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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
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Review
Schlagwörter 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
Sprache englisch
Veröffentlichungsjahr 2021
HGF-Berichtsjahr 2021
ISSN (print) / ISBN 1354-3776
e-ISSN 1744-7674
Zeitschrift Expert Opinion on Therapeutic Patents
Quellenangaben Band: 31, Heft: 12, Seiten: 1079-1096 Artikelnummer: , Supplement: ,
Verlag Taylor & Francis
Verlagsort 2-4 Park Square, Milton Park, Abingdon Or14 4rn, Oxon, England
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Signaling and Translation (SAT)
Institute of Medicinal Chemistry (IMC)
POF Topic(s) 30203 - Molecular Targets and Therapies
Forschungsfeld(er) Enabling and Novel Technologies
PSP-Element(e) G-509800-002
G-506300-001
Förderungen Deutsche Forschungsgemeinschaft
DOI 10.1080/13543776.2021.1951703
WOS ID WOS:000673869000001
Scopus ID 85110810359
PubMed ID 34214002
Erfassungsdatum 2021-07-27
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