ArticleNature communications2018
Inhalation of the prodrug PI3K inhibitor CL27c improves lung function in asthma and fibrosis.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 118 citations in OpenAlex.
- Roles of PI3K pan-inhibitors and PI3K-δ inhibitors in allergic lung inflammation: a systematic review and meta-analysis.Scientific reports · 2020Pooled it
- Zwitterion-Based Polymeric Carriers for Efficient Drug Delivery across Biological Barriers.Polymer science & technology (Washington, D.C.) · 2026Review
- Breaking the bottleneck of asthma treatment: the future of omni-targeted therapy.Journal of advanced research · 2026Review
- A renaissance in targeting the PI3K/AKT/mTOR pathway.Nature reviews. Drug discovery · 2026Review
- Fibrinogen-like protein 2 regulates inflammatory and metabolic reprogramming of airway smooth muscle cells through PI3K/Akt activation.Frontiers in medicine · 2026Article
- Evaluating the Anti-inflammatory Potential of JN-KI3: The Therapeutic Role of PI3Kγ-Selective Inhibitors in Asthma Treatment.Inflammation · 2025Article
- Budesonide-incorporated inhalable lipid nanoparticles for antiTSLP nanobody mRNA delivery to treat steroid-resistant asthma.Nature communications · 2025Article
- PI3K Inhibitors as Potential Therapeutic Agents for the Treatment of COPD with Associated Atherosclerosis.Drugs · 2025Review
- Integration of network pharmacology and experimental validation to explore the pharmacological mechanism of andrographolide against asthma.Bioresources and bioprocessing · 2025Article
- Genetic variation reveals the therapeutic potential of BRSK2 in idiopathic pulmonary fibrosis.BMC medicine · 2025Article
- PI3K/Akt in IPF: untangling fibrosis and charting therapies.Frontiers in immunology · 2025Review
- The Mechanisms and Therapeutic Implications of PI3K Signaling in Airway Inflammation and Remodeling in Asthma.Biologics : targets & therapy · 2025Review
- Inhalation of itraconazole mitigates bleomycin-induced lung fibrosis via regulating SPP1 and C3 signaling pathway pivotal in the interaction between phagocytic macrophages and diseased fibroblasts.Journal of translational medicine · 2024Article
- Opposite effects of systemic and local conditional CD11c+ myeloid cell depletion during bleomycin-induced inflammation and fibrosis in mice.Immunity, inflammation and disease · 2024Article
- Pharmacological Treatment of Interstitial Lung Diseases: A Novel Landscape for Inhaled Agents.Pharmaceutics · 2024Review
- Article
- Molecular basis for Gβγ-mediated activation of phosphoinositide 3-kinase γ.Nature structural & molecular biology · 2024Article
- Inhibition of phosphoinositide 3-kinase activity attenuates neutrophilic airway inflammation and inhibits pyrin domain-containing 3 inflammasome activation in an ovalbumin-lipopolysaccharide-induced asthma murine model.Molecular biology reports · 2024Article
- Novel inhalation therapy in pulmonary fibrosis: principles, applications and prospects.Journal of nanobiotechnology · 2024Review
- Article
Corrections and comments
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Authors and funding
23 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PI3K activation plays a central role in the development of pulmonary inflammation and tissue remodeling. PI3K inhibitors may thus offer an improved therapeutic opportunity to treat non-resolving lung inflammation but their action is limited by unwanted on-target systemic toxicity. Here we present CL27c, a prodrug pan-PI3K inhibitor designed for local therapy, and investigate whether inhaled CL27c is effective in asthma and pulmonary fibrosis. Mice inhaling CL27c show reduced insulin-evoked Akt phosphorylation in lungs, but no change in other tissues and no increase in blood glycaemia, in line with a local action. In murine models of acute or glucocorticoid-resistant neutrophilic asthma, inhaled CL27c reduces inflammation and improves lung function. Finally, inhaled CL27c administered in a therapeutic setting protects from bleomycin-induced lung fibrosis, ultimately leading to significantly improved survival. Therefore, local delivery of a pan-PI3K inhibitor prodrug reduces systemic on-target side effects but effectively treats asthma and irreversible pulmonary fibrosis.
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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.