ArticlePloS one2017
Bruton's tyrosine kinase inhibitor BMS-986142 in experimental models of rheumatoid arthritis enhances efficacy of agents representing clinical standard-of-care.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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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
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Bruton's Tyrosine Kinase (BTK) Inhibitors and Autoimmune Diseases: Making Sense of BTK Inhibitor Specificity Profiles and Recent Clinical Trial Successes and Failures.Frontiers in immunology · 2021Pooled it
- Bruton's Tyrosine Kinase Inhibitors: Mechanisms, Efficacy, Toxicities and Applications for the Treatment of Human Diseases.MedComm · 2026Review
- Discovery of Reversible, Noncovalent Bruton's Tyrosine Kinase Inhibitors Targeting BTK C481S Mutation.ACS medicinal chemistry letters · 2025Article
- Review
- Targeting Bruton's tyrosine kinase (BTK) as a signaling pathway in immune-mediated diseases: from molecular mechanisms to leading treatments.Advances in rheumatology (London, England) · 2024Review
- LIMS-Kinase provides sensitive and generalizable label-freeCell reports. Physical science · 2023Article
- Synthesis of 3-(Pyridin-2-yl)quinazolin-2,4(1International journal of molecular sciences · 2023Article
- A lesion-selective albumin-CTLA4Ig as a safe and effective treatment for collagen-induced arthritis.Inflammation and regeneration · 2023Article
- Article
- The spectrum of B cells in the pathogenesis, diagnosis and therapeutic applications of immunoglobulin G4-related disease.Clinical & translational immunology · 2023Review
- BTK inhibitors in the treatment of hematological malignancies and inflammatory diseases: mechanisms and clinical studies.Journal of hematology & oncology · 2022Review
- Bruton's Kinase Inhibitors for the Treatment of Immunological Diseases: Current Status and Perspectives.Journal of clinical medicine · 2022Review
- BTK inhibition limits B-cell-T-cell interaction through modulation of B-cell metabolism: implications for multiple sclerosis therapy.Acta neuropathologica · 2022Article
- Bruton's Tyrosine Kinase Inhibition as an Emerging Therapy in Systemic Autoimmune Disease.Drugs · 2021Review
- Recent Advances in BTK Inhibitors for the Treatment of Inflammatory and Autoimmune Diseases.Molecules (Basel, Switzerland) · 2021Review
- Safety, pharmacokinetics and pharmacodynamics of BI 705564, a highly selective, covalent inhibitor of Bruton's tyrosine kinase, in Phase I clinical trials in healthy volunteers.British journal of clinical pharmacology · 2021Article
- Therapeutic Advances in Diabetes, Autoimmune, and Neurological Diseases.International journal of molecular sciences · 2021Review
- Review
- Bruton's Tyrosine Kinase Inhibition for the Treatment of Rheumatoid Arthritis.ImmunoTargets and therapy · 2021Review
- Kinase inhibition in autoimmunity and inflammation.Nature reviews. Drug discovery · 2021Review
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bruton's tyrosine kinase (BTK) regulates critical signal transduction pathways involved in the pathobiology of rheumatoid arthritis (RA) and other autoimmune disorders. BMS-986142 is a potent and highly selective reversible small molecule inhibitor of BTK currently being investigated in clinical trials for the treatment of both RA and primary Sjögren's syndrome. In the present report, we detail the in vitro and in vivo pharmacology of BMS-986142 and show this agent provides potent and selective inhibition of BTK (IC50 = 0.5 nM), blocks antigen receptor-dependent signaling and functional endpoints (cytokine production, co-stimulatory molecule expression, and proliferation) in human B cells (IC50 ≤ 5 nM), inhibits Fcγ receptor-dependent cytokine production from peripheral blood mononuclear cells, and blocks RANK-L-induced osteoclastogenesis. Through the benefits of impacting these important drivers of autoimmunity, BMS-986142 demonstrated robust efficacy in murine models of rheumatoid arthritis (RA), including collagen-induced arthritis (CIA) and collagen antibody-induced arthritis (CAIA). In both models, robust efficacy was observed without continuous, complete inhibition of BTK. When a suboptimal dose of BMS-986142 was combined with other agents representing the current standard of care for RA (e.g., methotrexate, the TNFα antagonist etanercept, or the murine form of CTLA4-Ig) in the CIA model, improved efficacy compared to either agent alone was observed. The results suggest BMS-986142 represents a potential therapeutic for clinical investigation in RA, as monotherapy or co-administered with agents with complementary mechanisms of action.
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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.