ArticleScientific reports2022
The pan-JAK inhibitor LAS194046 reduces neutrophil activation from severe asthma and COPD patients in vitro.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Different inhaled corticosteroid doses in triple therapy for chronic obstructive pulmonary disease: systematic review and Bayesian network meta-analysis.Scientific reports · 2022Pooled it
- Sequential inspiratory muscle exercise-noninvasive positive pressure ventilation alleviates oxidative stress in COPD by mediating SOCS5/JAK2/STAT3 pathway.BMC pulmonary medicine · 2023Trial
- From clinical phenotypes to cellular mechanisms: a precision medicine framework for COPD.Frontiers in immunology · 2026Review
- Interleukin-23 in lung and airway diseases: from pathogenesis to precision-guided therapeutic targeting.Frontiers in pharmacology · 2026Review
- Identification ofFrontiers in immunology · 2026Review
- The methyl-CpG binding domain 2 regulates peptidylarginine deiminase 4 expression and promotes neutrophil extracellular trap formation via the Janus kinase 2 signaling pathway in experimental severe asthma.Annals of medicine · 2025Article
- Targeted biologic therapies and advanced drug delivery approaches in asthma management: a clinical perspective.Inflammopharmacology · 2025Review
- Structural and Functional Studies on Key Epigenetic Regulators in Asthma.Biomolecules · 2025Review
- Molecular Approaches to Treating Chronic Obstructive Pulmonary Disease: Current Perspectives and Future Directions.International journal of molecular sciences · 2025Review
- Review
- Selectivity, efficacy and safety of JAKinibs: new evidence for a still evolving story.Annals of the rheumatic diseases · 2024Review
- Role and regulators of NFrontiers in pharmacology · 2024Review
- Protein kinases: drug targets for immunological disorders.Nature reviews. Immunology · 2023Review
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Non-T2 severe asthma and chronic obstructive pulmonary disease (COPD) are airway chronic inflammatory disorders with a poor response to corticosteroids. LAS194046, a novel pan-Janus kinase (JAK) inhibitor, shows inhibitory effects on T2 allergic lung inflammation in rats. In this work we analyze the effects of LAS194046, fluticasone propionate and their combination in neutrophils from non-T2 severe asthma and COPD patients in vitro. Neutrophils from 23 healthy subjects, 23 COPD and 21 non-T2 severe asthma patients were incubated with LAS194046 (0.01 nM-1 µM), fluticasone propionate (0.1 nM-1 µM) or their combination and stimulated with lipopolysaccharide (LPS 1 µM). LAS194046 shows similar maximal % inhibition and potency inhibiting IL-8, MMP-9 and superoxide anion release in neutrophils from healthy, COPD and asthma. Fluticasone propionate suppresses mediator release only in neutrophils from healthy patients. The combination of LAS194046 with fluticasone propionate shows synergistic anti-inflammatory and anti-oxidant effects. The mechanisms involved in the synergistic effects of this combination include the increase of MKP1 expression, decrease of PI3Kδ, the induction of glucocorticoid response element and the decrease of ERK1/2, P38 and JAK2/STAT3 phosphorylation compared with monotherapies. In summary, LAS194046 shows anti-inflammatory effects in neutrophils from COPD and severe non-T2 asthma patients and induces synergistic anti-inflammatory effects when combined with fluticasone propionate.
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