ArticleAllergy and asthma proceedings
C-027 inhibits IgE-mediated passive sensitization bronchoconstriction and acts as a histamine and serotonin antagonist in human airways.
Article in Allergy and asthma proceedings. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 27 citations in OpenAlex.
- Cryopreservation of human lung tissue for 3D ex vivo analysis.Respiratory research · 2025Review
- Precision cut lung slices: an integrated ex vivo model for studying lung physiology, pharmacology, disease pathogenesis and drug discovery.Respiratory research · 2024Review
- Slicing through the challenge of maintainingmBio · 2024Article
- Precision-cut lung slices as anmBio · 2024Article
- The Bronchoprotective Effects of Dual Pharmacology, Muscarinic Receptor Antagonist and βCells · 2023Article
- Functional changes in long-term incubated rat precision-cut lung slices.Respiratory research · 2022Article
- The Use of Precision-Cut Lung Slices for Studying Innate Immunity to Viral Infections.Current protocols · 2022Article
- Organotypic Models of Lung Cancer.Current topics in microbiology and immunology · 2021Article
- Use of precision cut lung slices as a translational model for the study of lung biology.Respiratory research · 2019Review
- Salicylic acid amplifies Carbachol-induced bronchoconstriction in human precision-cut lung slices.Respiratory research · 2019Article
- Evaluation of inflammatory and immune responses in long-term cultured human precision-cut lung slices.Human vaccines & immunotherapeutics · 2017Article
- Assessment of long-term cultivated human precision-cut lung slices as an ex vivo system for evaluation of chronic cytotoxicity and functionality.Journal of occupational medicine and toxicology (London, England) · 2017Article
- Inhibition of spleen tyrosine kinase attenuates IgE-mediated airway contraction and mediator release in human precision cut lung slices.British journal of pharmacology · 2016Article
- Soluble guanylate cyclase as an alternative target for bronchodilator therapy in asthma.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Mapping physiological G protein-coupled receptor signaling pathways reveals a role for receptor phosphorylation in airway contraction.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Interdicting Gq Activation in Airway Disease by Receptor-Dependent and Receptor-Independent Mechanisms.Molecular pharmacology · 2016Article
- Glycogen synthase kinase-3β modulation of glucocorticoid responsiveness in COPD.American journal of physiology. Lung cellular and molecular physiology · 2015Article
- Persistence of serotonergic enhancement of airway response in a model of childhood asthma.American journal of respiratory cell and molecular biology · 2014Article
- Reproducible uniform equibiaxial stretch of precision-cut lung slices.American journal of physiology. Lung cellular and molecular physiology · 2013Article
- Trichostatin A abrogates airway constriction, but not inflammation, in murine and human asthma models.American journal of respiratory cell and molecular biology · 2012Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Atopic asthma is poorly controlled by current therapies. Newer therapies and novel antihistamines are, therefore, required to treat patients whose atopic asthma is not controlled. For the first time, C-027 is shown to antagonize histamine, IgE-mediated and serotonin-induced contraction in human airways and vessels. Human precision-cut lung slices (PCLS, 250 μm thick), containing an airway or blood vessel, were pretreated with either C-027 (2 hours) or with vehicle alone and were contracted with histamine or serotonin. Known antihistamine was used as a comparator in antihistamine studies. Also, human airways were contracted via IgE passive sensitization in the presence or absence of C-027 or fexofenadine. Affinity of C-027 toward human G-protein coupled receptors was also determined, as well as the drug's biodistribution in murine model. C-027 was shown to have the highest affinity toward human histamine and serotonin receptors. Subsequently, C-027 was shown to antagonize histamine- and serotonin-induced airway and vascular smooth muscle contraction, respectively, and histamine-released bronchocontraction mediated by IgE passive sensitization in human small airways. C-027 also inhibited histamine-mediated single-cell calcium ion release. Low levels of C-027 were found in murine brain tissue. Collectively, these data suggest that C-027 markedly inhibits IgE-induced bronchoconstriction and antagonizes histamine and serotonin-contraction with little biodistribution in the brain. The compound may offer a future therapy for allergen-induced airway hyperresponsiveness in patients with asthma.
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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.