ArticleInternational journal of molecular sciences2020
A Novel, Pan-PDE Inhibitor Exerts Anti-Fibrotic Effects in Human Lung Fibroblasts via Inhibition of TGF-β Signaling and Activation of cAMP/PKA Signaling.
Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 48 citations in OpenAlex.
- Multitarget Strategy for Treatment of Pulmonary Arterial Hypertension: Combination of Mesenchymal Cells with Novel PDE-4 Inhibitor.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Mechanistic basis for the antifibrotic actions of cAMP-based therapies.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Antifibrotic Strategies Targeting Phosphodiesterase-4 in Idiopathic Pulmonary Fibrosis: Molecular Mechanisms and Clinical Translation.Clinical pharmacology : advances and applications · 2026Review
- Variable steady inflammation and inflammatory responses in precision-cut lung slices from various IPF lung Regions.Respiratory research · 2025Article
- PDE4-Selective Inhibition in Chronic Obstructive Pulmonary Disease and Pulmonary Fibrosis: Different Agents or Different Targets?Life (Basel, Switzerland) · 2025Review
- BCG induced innate immune response heterogeneity and susceptibility to pediatric tuberculosis.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Inhalable Carbonyl Sulfide Donor-Hybridized Selective Phosphodiesterase 10A Inhibitor for Treating Idiopathic Pulmonary Fibrosis by Inhibiting Tumor Growth Factor-β Signaling and Activating the cAMP/Protein Kinase A/cAMP Response Element-Binding Protein (CREB)/p53 Axis.ACS pharmacology & translational science · 2025Article
- Shared immunological pathways in rheumatoid arthritis-related interstitial lung disease.Frontiers in immunology · 2025Review
- Article
- PMFrontiers in public health · 2025Article
- Nobiletin, as a Novel PDE4B Inhibitor, Alleviates Asthma Symptoms by Activating the cAMP-PKA-CREB Signaling Pathway.International journal of molecular sciences · 2024Article
- The Role of Transforming Growth Factor-β (TGF-β) in Asthma and Chronic Obstructive Pulmonary Disease (COPD).Cells · 2024Review
- Potential Rheumatoid Arthritis-Associated Interstitial Lung Disease Treatment and Computational Approach for Future Drug Development.International journal of molecular sciences · 2024Review
- cAMP-PKA/EPAC signaling and cancer: the interplay in tumor microenvironment.Journal of hematology & oncology · 2024Review
- Transcriptomics reveals age-related changes in ion transport-related factors in yak lungs.Frontiers in veterinary science · 2024Article
- CRTC2 activates the epithelial-mesenchymal transition of diabetic kidney disease through the CREB-Smad2/3 pathway.Molecular medicine (Cambridge, Mass.) · 2023Article
- Activation of TRPA1 in Bladder Suburothelial Myofibroblasts Counteracts TGF-β1-Induced Fibrotic Changes.International journal of molecular sciences · 2023Article
- Phosphodiesterase type 10A inhibitor attenuates lung fibrosis by targeting myofibroblast activation.iScience · 2023Article
- A phosphodiesterase-4 inhibitor reduces lung inflammation and fibrosis in a hamster model of SARS-CoV-2 infection.Frontiers in immunology · 2023Article
- Perspectives of PDE inhibitor on treating idiopathic pulmonary fibrosis.Frontiers in pharmacology · 2023Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Phosphodiesterase (PDE) inhibitors are currently a widespread and extensively studied group of anti-inflammatory and anti-fibrotic compounds which may find use in the treatment of numerous lung diseases, including asthma and chronic obstructive pulmonary disease. Several PDE inhibitors are currently in clinical development, and some of them, e.g., roflumilast, are already recommended for clinical use. Due to numerous reports indicating that elevated intracellular cAMP levels may contribute to the alleviation of inflammation and airway fibrosis, new and effective PDE inhibitors are constantly being sought. Recently, a group of 7,8-disubstituted purine-2,6-dione derivatives, representing a novel and prominent pan-PDE inhibitors has been synthesized. Some of them were reported to modulate transient receptor potential ankyrin 1 (TRPA1) ion channels as well. In this study, we investigated the effect of selected derivatives (832-a pan-PDE inhibitor, 869-a TRPA1 modulator, and 145-a pan-PDE inhibitor and a weak TRPA1 modulator) on cellular responses related to airway remodeling using MRC-5 human lung fibroblasts. Compound 145 exerted the most considerable effect in limiting fibroblast to myofibroblasts transition (FMT) as well as proliferation, migration, and contraction. The effect of this compound appeared to depend mainly on its strong PDE inhibitory properties, and not on its effects on TRPA1 modulation. The strong anti-remodeling effects of 145 required activation of the cAMP/protein kinase A (PKA)/cAMP response element-binding protein (CREB) pathway leading to inhibition of transforming growth factor type β
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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.