Details
| Original language | English |
|---|---|
| Pages (from-to) | 639-656 |
| Number of pages | 18 |
| Journal | Expert Opinion on Therapeutic Patents |
| Volume | 35 |
| Issue number | 6 |
| Early online date | 11 Apr 2025 |
| Publication status | Published - 2025 |
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.
Keywords
- allosteric inhibition, autoimmunity, cancer, lymphoma, MALT1, paracaspase, PROTAC, protease, regulatory T cells
ASJC Scopus subject areas
- Pharmacology, Toxicology and Pharmaceutics(all)
- Pharmacology
- Pharmacology, Toxicology and Pharmaceutics(all)
- Drug Discovery
Sustainable Development Goals
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In: Expert Opinion on Therapeutic Patents, Vol. 35, No. 6, 2025, p. 639-656.
Research output: Contribution to journal › Review article › Research › peer review
}
TY - JOUR
T1 - An updated patent review of MALT1 inhibitors (2021–present)
AU - Brvar, Matjaz
AU - O’Neill, Thomas J.
AU - Plettenburg, Oliver
AU - Krappmann, Daniel
N1 - Publisher Copyright: © 2025 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2025
Y1 - 2025
N2 - 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.
AB - 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.
KW - allosteric inhibition
KW - autoimmunity
KW - cancer
KW - lymphoma
KW - MALT1
KW - paracaspase
KW - PROTAC
KW - protease
KW - regulatory T cells
UR - http://www.scopus.com/inward/record.url?scp=105002365772&partnerID=8YFLogxK
U2 - 10.1080/13543776.2025.2484371
DO - 10.1080/13543776.2025.2484371
M3 - Review article
AN - SCOPUS:105002365772
VL - 35
SP - 639
EP - 656
JO - Expert Opinion on Therapeutic Patents
JF - Expert Opinion on Therapeutic Patents
SN - 1354-3776
IS - 6
ER -