ArticleThe Journal of clinical investigation2018
Specific covalent inhibition of MALT1 paracaspase suppresses B cell lymphoma growth.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
37 citing papers in PubMed, 58 citations in OpenAlex.
- MALT1 protease inhibition restrains glioblastoma progression by reversing tumor-associated macrophage-dependent immunosuppression in mice.Nature communications · 2026Article
- Therapeutic targeting of MALT1 in oncology: Mechanism, inhibitor development, and clinical prospects.Journal of cell communication and signaling · 2026Review
- miR-155 aberrant expression impairs tumor rejection because of its targeting of ICOSL and multiple pathways implicated in the antitumor response.Pharmacological reviews · 2026Review
- A small-molecule inhibitor of BCL10-MALT1 interaction abrogates progression of diffuse large B cell lymphoma.The Journal of clinical investigation · 2025Article
- Profiling the activity of the para-caspase MALT1 in B-cell acute lymphoblastic leukemia for potential targeted therapeutic application.Haematologica · 2024Article
- In silico study of polyphenols as potential inhibitors of MALT1 protein in non-Hodgkin lymphoma.Medical oncology (Northwood, London, England) · 2023Article
- Oncogene-induced MALT1 protease activity drives posttranscriptional gene expression in malignant lymphomas.Blood · 2023Article
- Structure-function study of a CaProceedings of the National Academy of Sciences of the United States of America · 2023Article
- MALT1-dependent cleavage of CYLD promotes NF-κB signaling and growth of aggressive B-cell receptor-dependent lymphomas.Blood cancer journal · 2023Article
- Combining precision oncology and immunotherapy by targeting the MALT1 protease.Journal for immunotherapy of cancer · 2022Review
- BCL10 Mutations Define Distinct Dependencies Guiding Precision Therapy for DLBCL.Cancer discovery · 2022Article
- MALT1 in asthma children: A potential biomarker for monitoring exacerbation risk and Th1/Th2 imbalance-mediated inflammation.Journal of clinical laboratory analysis · 2022Article
- The resistance mechanisms and treatment strategies of BTK inhibitors in B-cell lymphoma.Hematological oncology · 2021Review
- Review
- CARMA1 is required for Notch1-induced NF-κB activation in SIL-TAL1-negative T cell acute lymphoblastic leukemia.Journal of molecular medicine (Berlin, Germany) · 2021Article
- The PD-1/PD-L1 Checkpoint in Normal Germinal Centers and Diffuse Large B-Cell Lymphomas.Cancers · 2021Review
- Article
- MALT1-Dependent Cleavage of HOIL1 Modulates Canonical NF-κB Signaling and Inflammatory Responsiveness.Frontiers in immunology · 2021Article
- Article
- Article
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 3 countries.
Funding
Abstract
The paracaspase MALT1 plays an essential role in activated B cell-like diffuse large B cell lymphoma (ABC DLBCL) downstream of B cell and TLR pathway genes mutated in these tumors. Although MALT1 is considered a compelling therapeutic target, the development of tractable and specific MALT1 protease inhibitors has thus far been elusive. Here, we developed a target engagement assay that provides a quantitative readout for specific MALT1-inhibitory effects in living cells. This enabled a structure-guided medicinal chemistry effort culminating in the discovery of pharmacologically tractable, irreversible substrate-mimetic compounds that bind the MALT1 active site. We confirmed that MALT1 targeting with compound 3 is effective at suppressing ABC DLBCL cells in vitro and in vivo. We show that a reduction in serum IL-10 levels exquisitely correlates with the drug pharmacokinetics and degree of MALT1 inhibition in vitro and in vivo and could constitute a useful pharmacodynamic biomarker to evaluate these compounds in clinical trials. Compound 3 revealed insights into the biology of MALT1 in ABC DLBCL, such as the role of MALT1 in driving JAK/STAT signaling and suppressing the type I IFN response and MHC class II expression, suggesting that MALT1 inhibition could prime lymphomas for immune recognition by cytotoxic immune cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.