ArticleNature chemical biology2011
Specific Btk inhibition suppresses B cell- and myeloid cell-mediated arthritis.
Article in Nature chemical biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
141 citing papers in PubMed, 329 citations in OpenAlex.
- Docirbrutinib is a pan-mutant BTK inhibitor and inhibits B-cell receptor signaling in chronic lymphocytic leukemia cells in preclinical and early clinical investigations.Blood cancer journal · 2026Trial
- Safety, pharmacokinetics and pharmacodynamics of branebrutinib (BMS-986195), a covalent, irreversible inhibitor of Bruton's tyrosine kinase: Randomised phase I, placebo-controlled trial in healthy participants.British journal of clinical pharmacology · 2020Trial
- A phase I trial of PRN1008, a novel reversible covalent inhibitor of Bruton's tyrosine kinase, in healthy volunteers.British journal of clinical pharmacology · 2017Trial
- Safety, pharmacokinetics, and pharmacodynamics of BMS-986142, a novel reversible BTK inhibitor, in healthy participants.European journal of clinical pharmacology · 2017Trial
- Bruton's Tyrosine Kinase Inhibitors: Mechanisms, Efficacy, Toxicities and Applications for the Treatment of Human Diseases.MedComm · 2026Review
- Article
- Small-Molecule Drugs Approved by the FDA in 2025.Molecules (Basel, Switzerland) · 2026Review
- Mechanisms of resistance to BTK inhibitors in B cell malignancies and emerging targeted strategies.Molecular therapy. Oncology · 2026Review
- Review
- Profiling protein post-translational modifications in plasma-derived extracellular vesicles as fingerprints for breast cancer subtypes.Genome biology · 2026Article
- Review
- Inhibition of bruton's tyrosine kinase directly alleviates pathogenic CD4+ T cell response via PPAR-γ signaling in autoimmune uveitis.Journal of neuroinflammation · 2025Article
- Modulating the Binding Kinetics of Bruton's Tyrosine Kinase Inhibitors through Transition-State Effects.Journal of the American Chemical Society · 2025Article
- Targeting rheumatoid arthritis: a molecular perspective on biologic therapies and clinical progress.Journal of biological engineering · 2025Review
- Streamlining SuFEx Inhibitor Development: A Unified Approach Using Photolabile and Orthogonal Sulfinate Protecting Groups.Angewandte Chemie (International ed. in English) · 2025Article
- BTK inhibitors and next-generation BTK-targeted therapeutics for B-cell malignancies.Archives of pharmacal research · 2025Review
- Comprehensive Characterization of Bruton's Tyrosine Kinase Inhibitor Specificity, Potency, and Biological Effects: Insights into Covalent and Noncovalent Mechanistic Signatures.ACS pharmacology & translational science · 2025Review
- From development to clinical success: the journey of established and next-generation BTK inhibitors.Investigational new drugs · 2025Review
- A Case Series and Literature Review on Zanubrutinib Therapy for the Treatment of Relapsed/Refractory Immune Thrombocytopenia.Cancer reports (Hoboken, N.J.) · 2025Review
- Sequelae of B-Cell Depleting Therapy: An Immunologist's Perspective.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
81 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
31 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bruton's tyrosine kinase (Btk) is a therapeutic target for rheumatoid arthritis, but the cellular and molecular mechanisms by which Btk mediates inflammation are poorly understood. Here we describe the discovery of CGI1746, a small-molecule Btk inhibitor chemotype with a new binding mode that stabilizes an inactive nonphosphorylated enzyme conformation. CGI1746 has exquisite selectivity for Btk and inhibits both auto- and transphosphorylation steps necessary for enzyme activation. Using CGI1746, we demonstrate that Btk regulates inflammatory arthritis by two distinct mechanisms. CGI1746 blocks B cell receptor-dependent B cell proliferation and in prophylactic regimens reduces autoantibody levels in collagen-induced arthritis. In macrophages, Btk inhibition abolishes FcγRIII-induced TNFα, IL-1β and IL-6 production. Accordingly, in myeloid- and FcγR-dependent autoantibody-induced arthritis, CGI1746 decreases cytokine levels within joints and ameliorates disease. These results provide new understanding of the function of Btk in both B cell- or myeloid cell-driven disease processes and provide a compelling rationale for targeting Btk in rheumatoid arthritis.
Indexed as
Identifiers
What OpenQuestion holds
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.