ArticleChemistry & biology2015
Inflammatory Signaling by NOD-RIPK2 Is Inhibited by Clinically Relevant Type II Kinase Inhibitors.
Article in Chemistry & biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
What it found
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Who cites it
60 citing papers in PubMed, 123 citations in OpenAlex.
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- Structural basis for MEKK2 dimerization and substrate recognition.Nature communications · 2025Article
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- ImmunoMet Oncogenesis: A New Concept to Understand the Molecular Drivers of Cancer.Journal of clinical medicine · 2025Review
- Current advances on RIPK2 and its inhibitors in pathological processes: a comprehensive review.Frontiers in molecular neuroscience · 2025Review
- An exploratory single-cell analysis of peripheral blood mononuclear cells from vedolizumab-treated Crohn's disease patients identifies response-associated differences among the plasmacytoid dendritic cells and classical monocytes.Frontiers in immunology · 2025Article
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- Recent insights of PROTAC developments in inflammation-mediated and autoimmune targets: a critical review.RSC medicinal chemistry · 2024Review
- Structure-based development of potent and selective type-II kinase inhibitors of RIPK1.Acta pharmaceutica Sinica. B · 2024Article
- Design, synthesis and biological evaluation of 4-aminoquinoline derivatives as receptor-interacting protein kinase 2 (RIPK2) inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- Structure shows that the BIR2 domain of E3 ligase XIAP binds across the RIPK2 kinase dimer interface.Life science alliance · 2023Article
- A Cell Type Selective YM155 Prodrug Targets Receptor-Interacting Protein Kinase 2 to Induce Brain Cancer Cell Death.Journal of the American Chemical Society · 2023Article
- Network expansion of genetic associations defines a pleiotropy map of human cell biology.Nature genetics · 2023Article
- scDual-Seq ofFrontiers in immunology · 2023Article
- RIPK2: a promising target for cancer treatment.Frontiers in pharmacology · 2023Review
- Recent advances in the development of RIPK2 modulators for the treatment of inflammatory diseases.Frontiers in pharmacology · 2023Review
- Application and prospect of targeting innate immune sensors in the treatment of autoimmune diseases.Cell & bioscience · 2022Review
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
Abstract
RIPK2 mediates pro-inflammatory signaling from the bacterial sensors NOD1 and NOD2, and is an emerging therapeutic target in autoimmune and inflammatory diseases. We observed that cellular RIPK2 can be potently inhibited by type II inhibitors that displace the kinase activation segment, whereas ATP-competitive type I inhibition was only poorly effective. The most potent RIPK2 inhibitors were the US Food and Drug Administration-approved drugs ponatinib and regorafenib. Their mechanism of action was independent of NOD2 interaction and involved loss of downstream kinase activation as evidenced by lack of RIPK2 autophosphorylation. Notably, these molecules also blocked RIPK2 ubiquitination and, consequently, inflammatory nuclear factor κB signaling. In monocytes, the inhibitors selectively blocked NOD-dependent tumor necrosis factor production without affecting lipopolysaccharide-dependent pathways. We also determined the first crystal structure of RIPK2 bound to ponatinib, and identified an allosteric site for inhibitor development. These results highlight the potential for type II inhibitors to treat indications of RIPK2 activation as well as inflammation-associated cancers.
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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.