ArticleJournal of immunology (Baltimore, Md. : 1950)2017
Selective IRAK4 Inhibition Attenuates Disease in Murine Lupus Models and Demonstrates Steroid Sparing Activity.
Article in Journal of immunology (Baltimore, Md. : 1950), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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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
41 citing papers in PubMed, 73 citations in OpenAlex.
- The oral IRAK4 inhibitors zabedosertib and BAY1830839 suppress local and systemic immune responses in a randomized trial in healthy male volunteers.Clinical and translational science · 2024Trial
- The Interleukin-1 Receptor-Associated Kinase 4 Inhibitor PF-06650833 Blocks Inflammation in Preclinical Models of Rheumatic Disease and in Humans Enrolled in a Randomized Clinical Trial.Arthritis & rheumatology (Hoboken, N.J.) · 2021Trial
- What's New in Cutaneous Lupus Erythematosus: Guidelines, Biologics, and Beyond.The Journal of clinical and aesthetic dermatology · 2026Review
- TLR7 and TLR9 have overlapping but distinct roles in systemic lupus erythematosus and Sjögren's disease.Frontiers in immunology · 2026Review
- Efficacy and Safety of Zabedosertib, an Interleukin-1 Receptor-Associated Kinase 4 Inhibitor, in Patients with Moderate-to-Severe Atopic Dermatitis: A Phase II Randomized Study.Dermatology and therapy · 2025Article
- Pharmacological Mechanism of Chinese Medicine in Systemic Lupus Erythematosus: A Narrative Review.Chinese journal of integrative medicine · 2025Review
- Signaling pathways in systemic lupus erythematosus and therapeutic implications.Frontiers in immunology · 2025Review
- Exploring the Potential of Pyridine Carboxylic Acid Isomers to Discover New Enzyme Inhibitors.Drug design, development and therapy · 2025Review
- Emerging interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitors or degraders as therapeutic agents for autoimmune diseases and cancer.Acta pharmaceutica Sinica. B · 2024Review
- Interleukin-1 receptor-associated kinase 4 (IRAK4) is a critical regulator of inflammatory signalling through toll-like receptors 4 and 7/8 in murine and human lungs.British journal of pharmacology · 2024Article
- IRAK4 is an immunological checkpoint in neuropsychiatric systemic lupus erythematosus.Scientific reports · 2024Article
- A Novel IRAK4 Inhibitor DW18134 Ameliorates Peritonitis and Inflammatory Bowel Disease.Molecules (Basel, Switzerland) · 2024Article
- IRAK4 inhibition: an effective strategy for immunomodulating peri-implant osseointegration via reciprocally-shifted polarization in the monocyte-macrophage lineage cells.BMC oral health · 2023Article
- Pacritinib abrogates the lupus phenotype in ABIN1[D485N] mice.Lupus science & medicine · 2023Article
- Neuroinflammation, autoinflammation, splenomegaly and anemia caused by bi-allelic mutations inFrontiers in immunology · 2023Article
- Oral IRAK4 inhibitor BAY-1834845 prevents acute respiratory distress syndrome.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022Article
- Nonhematopoietic IRAK1 drives arthritis via neutrophil chemoattractants.JCI insight · 2022Article
- Current Concepts on Pathogenic Mechanisms and Histopathology in Cutaneous Lupus Erythematosus.Frontiers in medicine · 2022Review
- Targeting the Myddosome in Systemic Autoimmunity: Ready for Prime Time?Arthritis & rheumatology (Hoboken, N.J.) · 2021Article
- Prevention and partial reversion of the lupus phenotype in ABIN1[D485N] mice by an IRAK4 inhibitor.Lupus science & medicine · 2021Article
Corrections and comments
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Authors and funding
25 authors at 2 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The serine/threonine kinase IL-1R-associated kinase (IRAK)4 is a critical regulator of innate immunity. We have identified BMS-986126, a potent, highly selective inhibitor of IRAK4 kinase activity that demonstrates equipotent activity against multiple MyD88-dependent responses both in vitro and in vivo. BMS-986126 failed to inhibit assays downstream of MyD88-independent receptors, including the TNF receptor and TLR3. Very little activity was seen downstream of TLR4, which can also activate an MyD88-independent pathway. In mice, the compound inhibited cytokine production induced by injection of several different TLR agonists, including those for TLR2, TLR7, and TLR9. The compound also significantly suppressed skin inflammation induced by topical administration of the TLR7 agonist imiquimod. BMS-986126 demonstrated robust activity in the MRL/lpr and NZB/NZW models of lupus, inhibiting multiple pathogenic responses. In the MRL/lpr model, robust activity was observed with the combination of suboptimal doses of BMS-986126 and prednisolone, suggesting the potential for steroid sparing activity. BMS-986126 also demonstrated synergy with prednisolone in assays of TLR7- and TLR9-induced IFN target gene expression using human PBMCs. Lastly, BMS-986126 inhibited TLR7- and TLR9-dependent responses using cells derived from lupus patients, suggesting that inhibition of IRAK4 has the potential for therapeutic benefit in treating lupus.
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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.