ArticleDrug design, development and therapy2022
Characterization of Selective and Potent JAK1 Inhibitors Intended for the Inhaled Treatment of Asthma.
Article in Drug design, development and therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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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.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- Phase 2a randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of londamocitinib (AZD4604) two times per day for 12 weeks in adult patients with moderate-to-severe asthma uncontrolled on medium-high-dose ICS-LABA.BMJ open respiratory research · 2026Trial
- AZD0449, an inhaled JAK1 inhibitor, in healthy participants and patients with mild asthma.British journal of clinical pharmacology · 2026Trial
- ARTEMISIA: a mechanistic study of a novel Janus kinase 1 inhibitor to advance molecular understanding and precision medicine in asthma.Respiratory research · 2025Trial
- Review
- Mechanisms and therapeutic strategies of asthma: from bench to bedside.Signal transduction and targeted therapy · 2026Review
- The JAK-STAT pathway in allergic diseases: from pathogenesis to targeted therapy.Biomarker research · 2026Review
- Breaking the bottleneck of asthma treatment: the future of omni-targeted therapy.Journal of advanced research · 2026Review
- Targeted biologic therapies and advanced drug delivery approaches in asthma management: a clinical perspective.Inflammopharmacology · 2025Review
- Unraveling the mechanisms of virus-induced asthma exacerbation: epithelial injury, immune dysregulation, and novel interventions.Chinese medical journal pulmonary and critical care medicine · 2025Review
- Naturally derived bioactive compounds as regulators of oxidative stress and inflammation in asthma.Chinese medicine · 2025Review
- Development of a Formulation and In Vitro Evaluation of a Pulmonary Drug Delivery System for a Novel Janus Kinase (JAK) Inhibitor, CPL409116.Pharmaceutics · 2024Article
- Applications of Flow Cytometry in Drug Discovery and Translational Research.International journal of molecular sciences · 2024Review
- Selectivity, efficacy and safety of JAKinibs: new evidence for a still evolving story.Annals of the rheumatic diseases · 2024Review
- Are peptidomimetics the compounds of choice for developing new modulators of the JAK-STAT pathway?Frontiers in immunology · 2024Review
- Protein kinases: drug targets for immunological disorders.Nature reviews. Immunology · 2023Review
- Selective Janus kinase 1 inhibition resolves inflammation and restores hair growth offering a viable treatment option for alopecia areata.Skin health and disease · 2023Article
- Exploration of the mechanism of Qi-Xian decoction in asthmatic mice using metabolomics combined with network pharmacology.Frontiers in molecular biosciences · 2023Article
Corrections and comments
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Authors and funding
27 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Purpose: Janus kinase 1 (JAK1) is implicated in multiple inflammatory pathways that are critical for the pathogenesis of asthma, including the interleukin (IL)-4, IL-5, IL-13, and thymic stromal lymphopoietin cytokine signaling pathways, which have previously been targeted to treat allergic asthma. Here, we describe the development of AZD0449 and AZD4604, two novel and highly selective JAK1 inhibitors with promising properties for inhalation. Methods: The effects of AZD0449 and AZD4604 in JAK1 signaling pathways were assessed by measuring phosphorylation of signal transducer and activator of transcription (STAT) proteins and chemokine release using immunoassays of whole blood from healthy human volunteers and rats. Pharmacokinetic studies performed on rats evaluated AZD0449 at a lung deposited dose of 52 μg/kg and AZD4604 at 30 µg/kg. The efficacy of AZD0449 and AZD4604 was assessed by evaluating lung inflammation (cell count and cytokine levels) and the late asthmatic response (average enhanced pause [Penh]). Results: Both compounds inhibited JAK1-dependent cytokine signaling pathways in a dose-dependent manner in human and rat leukocytes. After intratracheal administration in rats, both compounds exhibited low systemic exposures and medium-to-long terminal lung half-lives (AZD0449, 34 hours; AZD4604, 5 hours). Both compounds inhibited STAT3 and STAT5 phosphorylation in lung tissue from ovalbumin (OVA)-challenged rats. AZD0449 and AZD4604 also inhibited eosinophilia in the lung and reduced the late asthmatic response, measured as Penh in the OVA rat model. Conclusion: AZD0449 and AZD4604 show potential as inhibitors of signaling pathways involved in asthmatic immune responses, with target engagement demonstrated locally in the lung. These findings support the clinical development of AZD0449 and AZD4604 for the treatment of patients with asthma.
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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.