ArticleThorax2016
Exploration of a potent PI3 kinase/mTOR inhibitor as a novel anti-fibrotic agent in IPF.
Article in Thorax, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01725139 (A Randomised, Placebo-controlled, Double-blind, Repeat Dose Escalation Study With GSK2126458 in Patients With Idiopathic Pulmonary Fibrosis), which is not on this map. Cited by 113 papers.
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.
A Randomised, Placebo-controlled, Double-blind, Repeat Dose Escalation Study With GSK2126458 in Patients With Idiopathic Pulmonary Fibrosis (IPF)
Who cites it
113 citing papers in PubMed, 201 citations in OpenAlex.
- Fibronectin's tensional state as a mechanical signature of fibrotic extracellular matrix in idiopathic pulmonary fibrosis models.Matrix biology plus · 2026Article
- Decoding fibroblast activation: Transcriptional networks in hepatic stellate cells and across fibrotic organs (Review).International journal of molecular medicine · 2026Review
- 4E-BP1 acts as a molecular rheostat balancing regenerative healing and fibrotic scarring.Experimental & molecular medicine · 2026Article
- Hallmarks of the ageing lung: 10 years later.The European respiratory journal · 2026Review
- STIM/Orai-Mediated Store-Operated CaCells · 2026Review
- Targeting mTOR with vistusertib attenuates metabolic steatohepatitis and prevents HCC development.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Decoding organ fibrosis: mechanistic insights and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Tools of the trade: leveraging 3DFrontiers in pharmacology · 2026Review
- The importance of mechanical forces in chronic respiratory diseases.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Article
- Metabolic dysregulation in pulmonary fibrosis: insights into amino acid contributions and therapeutic potential.Cell death discovery · 2025Review
- Senotherapy for chronic lung disease.Pharmacological reviews · 2025Review
- Pulmonary fibrosis: from mechanisms to therapies.Journal of translational medicine · 2025Review
- Ratio of miRNA-29 to miRNA-199 expression coordinates mesenchymal stem cell repair of bleomycin-induced pulmonary injury.Molecular therapy. Nucleic acids · 2025Article
- 3,5,6,7,8,3',4'- Heptamethoxyflavonoid inhibits TGF-β1-induced epithelial-mesenchymal transition by regulating oxidative stress and autophagy through MEK/ERK/PI3K/AKT/mTOR signaling pathway.Scientific reports · 2025Article
- Precision-Cut Lung Slices: Emerging Tools for Preclinical and Translational Lung Research: An Official American Thoracic Society Workshop Report.American journal of respiratory cell and molecular biology · 2025Article
- Fibroblast PI3K/AKT signaling and extracellular matrix homeostasis: mechanisms, targets, and delivery challenges.Frontiers in cell and developmental biology · 2025Review
- PI3K/Akt in IPF: untangling fibrosis and charting therapies.Frontiers in immunology · 2025Review
- Targeting Fibrosis: From Molecular Mechanisms to Advanced Therapies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Overexpression of STX11 alleviates pulmonary fibrosis by inhibiting fibroblast activation via the PI3K/AKT/mTOR pathway.Signal transduction and targeted therapy · 2024Article
53 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
Abstract
rationaleIdiopathic pulmonary fibrosis (IPF) is the most rapidly progressive and fatal of all fibrotic conditions with no curative therapies. Common pathomechanisms between IPF and cancer are increasingly recognised, including dysfunctional pan-PI3 kinase (PI3K) signalling as a driver of aberrant proliferative responses. GSK2126458 is a novel, potent, PI3K/mammalian target of rapamycin (mTOR) inhibitor which has recently completed phase I trials in the oncology setting. Our aim was to establish a scientific and dosing framework for PI3K inhibition with this agent in IPF at a clinically developable dose.
methodsWe explored evidence for pathway signalling in IPF lung tissue and examined the potency of GSK2126458 in fibroblast functional assays and precision-cut IPF lung tissue. We further explored the potential of IPF patient-derived bronchoalveolar lavage (BAL) cells to serve as pharmacodynamic biosensors to monitor GSK2126458 target engagement within the lung.
resultsWe provide evidence for PI3K pathway activation in fibrotic foci, the cardinal lesions in IPF. GSK2126458 inhibited PI3K signalling and functional responses in IPF-derived lung fibroblasts, inhibiting Akt phosphorylation in IPF lung tissue and BAL derived cells with comparable potency. Integration of these data with GSK2126458 pharmacokinetic data from clinical trials in cancer enabled modelling of an optimal dosing regimen for patients with IPF.
conclusionsOur data define PI3K as a promising therapeutic target in IPF and provide a scientific and dosing framework for progressing GSK2126458 to clinical testing in this disease setting. A proof-of-mechanism trial of this agent is currently underway. TRIAL REGISTRATION NUMBER: NCT01725139, pre-clinical.
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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.