ArticleJournal of aerosol medicine and pulmonary drug delivery2016
Btk Inhibitor RN983 Delivered by Dry Powder Nose-only Aerosol Inhalation Inhibits Bronchoconstriction and Pulmonary Inflammation in the Ovalbumin Allergic Mouse Model of Asthma.
Article in Journal of aerosol medicine and pulmonary drug delivery, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- Current and future landscape of Bruton tyrosine kinase inhibitors in allergy.The Journal of allergy and clinical immunology · 2025Review
- Bruton's tyrosine kinase inhibition for the treatment of allergic disorders.Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology · 2024Review
- Type 2 chronic inflammatory diseases: targets, therapies and unmet needs.Nature reviews. Drug discovery · 2023Review
- Type 2 inflammation and biological therapies in asthma: Targeted medicine taking flight.The Journal of experimental medicine · 2023Review
- Investigational Treatments in Phase I and II Clinical Trials: A Systematic Review in Asthma.Biomedicines · 2022Review
- Inhibition of Bruton's Tyrosine Kinase Alleviates Monocrotaline-Induced Pulmonary Arterial Hypertension by Modulating Macrophage Polarization.Oxidative medicine and cellular longevity · 2022Article
- Transcriptomic Signatures and Functional Network Analysis of Chronic Rhinosinusitis With Nasal Polyps.Frontiers in genetics · 2021Article
- Potential Role of Mast Cells in Regulating Corticosteroid Insensitivity in Severe Asthma.Advances in experimental medicine and biology · 2021Article
- Targeting Bruton's Tyrosine Kinase in Inflammatory and Autoimmune Pathologies.Frontiers in cell and developmental biology · 2021Review
- Clinical efficacy of recombinant human latrophilin 3 antibody in the treatment of pediatric asthma.Experimental and therapeutic medicine · 2018Article
- Dry Powder and Nebulized Aerosol Inhalation of Pharmaceuticals Delivered to Mice Using a Nose-only Exposure System.Journal of visualized experiments : JoVE · 2017Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundIn allergen-induced asthma, activated mast cells start the lung inflammatory process with degranulation, cytokine synthesis, and mediator release. Bruton's tyrosine kinase (Btk) activity is required for the mast cell activation during IgE-mediated secretion.
methodsThis study characterized a novel inhaled Btk inhibitor RN983 in vitro and in ovalbumin allergic mouse models of the early (EAR) and late (LAR) asthmatic response.
resultsRN983 potently, selectively, and reversibly inhibited the Btk enzyme. RN983 displayed functional activities in human cell-based assays in multiple cell types, inhibiting IgG production in B-cells with an IC50 of 2.5 ± 0.7 nM and PGD2 production from mast cells with an IC50 of 8.3 ± 1.1 nM. RN983 displayed similar functional activities in the allergic mouse model of asthma when delivered as a dry powder aerosol by nose-only inhalation. RN983 was less potent at inhibiting bronchoconstriction (IC50(RN983) = 59 μg/kg) than the β-agonist salbutamol (IC50(salbutamol) = 15 μg/kg) in the mouse model of the EAR. RN983 was more potent at inhibiting the antigen induced increase in pulmonary inflammation (IC50(RN983) = <3 μg/kg) than the inhaled corticosteroid budesonide (IC50(budesonide) = 27 μg/kg) in the mouse model of the LAR.
conclusionsInhalation of aerosolized RN983 may be effective as a stand-alone asthma therapy or used in combination with inhaled steroids and β-agonists in severe asthmatics due to its potent inhibition of mast cell activation.
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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.