ArticleThe European respiratory journal2022
Inhaled seralutinib exhibits potent efficacy in models of pulmonary arterial hypertension.
Article in The European respiratory journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- Searching for Old and New Small-Molecule Protein Kinase Inhibitors as Effective Treatments in Pulmonary Hypertension-A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Seralutinib for the Treatment of Pulmonary Arterial Hypertension in Adults: TORREY Open-Label Extension Study.Advances in therapy · 2025Trial
- Navigating the Complexity of PH-ILD: From Molecular Mechanisms to Integrated Clinical Evaluation.International journal of molecular sciences · 2026Review
- Circulating biomarker results from a phase 2 study of seralutinib in pulmonary arterial hypertension.American journal of respiratory and critical care medicine · 2026Article
- The Evolving Landscape of Pulmonary Hypertension Treatment: From Vasodilation to Disease Modification.Clinical and translational science · 2026Review
- A Paradigm Shift of HCurrent issues in molecular biology · 2026Review
- Post-translational modification crosstalk in pulmonary arterial hypertension: mechanisms and therapeutic implications.Molecular biology reports · 2026Review
- Paradigm shift: from pulmonary vasodilation to cardiopulmonary dual-track therapy-a comprehensive review of pathophysiology and advances in pulmonary hypertension-associated right heart failure.Respiratory research · 2026Review
- Advances in Novel Therapeutic Strategies for Pulmonary Arterial Hypertension.Canadian respiratory journal · 2026Review
- Rewriting the vascular script: epigenetic modifiers as scribes of metabolic reprogramming in pulmonary hypertension.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Signaling pathways and targeted therapy for pulmonary hypertension.Signal transduction and targeted therapy · 2025Review
- Therapeutic targets for pulmonary arterial hypertension: insights into the emerging landscape.Expert opinion on therapeutic targets · 2025Review
- New therapies in pulmonary arterial hypertension: Recent insights.International journal of cardiology. Congenital heart disease · 2025Article
- Roles of PDGF/PDGFR signaling in various organs.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025Review
- Mechanistic insights into the role of EGLN3 in pulmonary vascular remodeling and endothelial dysfunction.Respiratory research · 2025Review
- Mechanisms and treatment of pulmonary arterial hypertension.Nature reviews. Cardiology · 2025Review
- Dysfunction in mitochondrial electron transport chain drives the pathogenesis of pulmonary arterial hypertension: insights from a multi-omics investigation.Respiratory research · 2025Article
- Precision Medicine for Pulmonary Vascular Disease: The Future Is Now (2023 Grover Conference Series).Pulmonary circulation · 2025Article
- Diagnosis and Management of Pulmonary Hypertension: New Insights.Diagnostics (Basel, Switzerland) · 2024Review
- Risk stratification refinements with inclusion of haemodynamic variables at follow-up in patients with pulmonary arterial hypertension.The European respiratory journal · 2024Article
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundSignalling through platelet-derived growth factor receptor (PDGFR), colony-stimulating factor 1 receptor (CSF1R) and mast/stem cell growth factor receptor kit (c-KIT) plays a critical role in pulmonary arterial hypertension (PAH). We examined the preclinical efficacy of inhaled seralutinib, a unique small-molecule PDGFR/CSF1R/c-KIT kinase inhibitor in clinical development for PAH, in comparison to a proof-of-concept kinase inhibitor, imatinib.
methodsSeralutinib and imatinib potency and selectivity were compared. Inhaled seralutinib pharmacokinetics/pharmacodynamics were studied in healthy rats. Efficacy was evaluated in two rat models of PAH: SU5416/Hypoxia (SU5416/H) and monocrotaline pneumonectomy (MCTPN). Effects on inflammatory/cytokine signalling were examined. PDGFR, CSF1R and c-KIT immunohistochemistry in rat and human PAH lung samples and microRNA (miRNA) analysis in the SU5416/H model were performed.
resultsSeralutinib potently inhibited PDGFRα/β, CSF1R and c-KIT. Inhaled seralutinib demonstrated dose-dependent inhibition of lung PDGFR and c-KIT signalling and increased bone morphogenetic protein receptor type 2 (BMPR2). Seralutinib improved cardiopulmonary haemodynamic parameters and reduced small pulmonary artery muscularisation and right ventricle hypertrophy in both models. In the SU5416/H model, seralutinib improved cardiopulmonary haemodynamic parameters, restored lung BMPR2 protein levels and decreased N-terminal pro-brain natriuretic peptide (NT-proBNP), more than imatinib. Quantitative immunohistochemistry in human lung PAH samples demonstrated increased PDGFR, CSF1R and c-KIT. miRNA analysis revealed candidates that could mediate seralutinib effects on BMPR2.
conclusionsInhaled seralutinib was an effective treatment of severe PAH in two animal models, with improved cardiopulmonary haemodynamic parameters, a reduction in NT-proBNP, reverse remodelling of pulmonary vascular pathology and improvement in inflammatory biomarkers. Seralutinib showed greater efficacy compared to imatinib in a preclinical study.
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