An updated patent review of MALT1 inhibitors (2021–present)

authored by

Matjaz Brvar, Thomas J. O’Neill, Oliver Plettenburg, Daniel Krappmann

Abstract

Introduction: MALT1 paracaspase acts as a 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 have 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 the 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.

Organisation(s)

Institute of Organic Chemistry
Centre of Biomolecular Drug Research (BMWZ)
Laboratory of Nano and Quantum Engineering

External Organisation(s)

Helmholtz Zentrum München - German Research Center for Environmental Health
Institute for Lung Health (ILH)
Ludwig-Maximilians-Universität München (LMU)

Type

Review article

Journal

Expert Opinion on Therapeutic Patents

ISSN

1354-3776

Publication date

11.04.2025

Publication status

E-pub ahead of print

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/10.1080/13543776.2025.2484371 (Access: Closed)