Nature Communications (Sep 2020)
Translational pharmacology of an inhaled small molecule αvβ6 integrin inhibitor for idiopathic pulmonary fibrosis
- Alison E. John,
- Rebecca H. Graves,
- K. Tao Pun,
- Giovanni Vitulli,
- Ellen J. Forty,
- Paul F. Mercer,
- Josie L. Morrell,
- John W. Barrett,
- Rebecca F. Rogers,
- Maryam Hafeji,
- Lloyd I. Bibby,
- Elaine Gower,
- Valerie S. Morrison,
- Yim Man,
- James A. Roper,
- Jeni C. Luckett,
- Lee A. Borthwick,
- Ben S. Barksby,
- Rachel A. Burgoyne,
- Rory Barnes,
- Joelle Le,
- David J. Flint,
- Susan Pyne,
- Anthony Habgood,
- Louise A. Organ,
- Chitra Joseph,
- Rochelle C. Edwards-Pritchard,
- Toby M. Maher,
- Andrew J. Fisher,
- Natasja Stæhr Gudmann,
- Diana J. Leeming,
- Rachel C. Chambers,
- Pauline T. Lukey,
- Richard P. Marshall,
- Simon J. F. Macdonald,
- R. Gisli Jenkins,
- Robert J. Slack
Affiliations
- Alison E. John
- Respiratory Medicine NIHR Biomedical Research Centre, University of Nottingham
- Rebecca H. Graves
- Fibrosis DPU, Respiratory TAU, GlaxoSmithKline
- K. Tao Pun
- Fibrosis DPU, Respiratory TAU, GlaxoSmithKline
- Giovanni Vitulli
- Fibrosis DPU, Respiratory TAU, GlaxoSmithKline
- Ellen J. Forty
- Centre for Inflammation and Tissue Repair, University College London
- Paul F. Mercer
- Centre for Inflammation and Tissue Repair, University College London
- Josie L. Morrell
- Fibrosis DPU, Respiratory TAU, GlaxoSmithKline
- John W. Barrett
- Fibrosis DPU, Respiratory TAU, GlaxoSmithKline
- Rebecca F. Rogers
- Fibrosis DPU, Respiratory TAU, GlaxoSmithKline
- Maryam Hafeji
- Fibrosis DPU, Respiratory TAU, GlaxoSmithKline
- Lloyd I. Bibby
- Fibrosis DPU, Respiratory TAU, GlaxoSmithKline
- Elaine Gower
- Fibrosis DPU, Respiratory TAU, GlaxoSmithKline
- Valerie S. Morrison
- Fibrosis DPU, Respiratory TAU, GlaxoSmithKline
- Yim Man
- Fibrosis DPU, Respiratory TAU, GlaxoSmithKline
- James A. Roper
- Fibrosis DPU, Respiratory TAU, GlaxoSmithKline
- Jeni C. Luckett
- Radiological Sciences, University of Nottingham
- Lee A. Borthwick
- Fibrosis Research Group, Newcastle University Biosciences Institute and Newcastle University Translational and Clinical Research Institute
- Ben S. Barksby
- Fibrosis Research Group, Newcastle University Biosciences Institute and Newcastle University Translational and Clinical Research Institute
- Rachel A. Burgoyne
- Fibrosis Research Group, Newcastle University Biosciences Institute and Newcastle University Translational and Clinical Research Institute
- Rory Barnes
- Fibrosis Research Group, Newcastle University Biosciences Institute and Newcastle University Translational and Clinical Research Institute
- Joelle Le
- Drug Design and Selection - Molecular Design, Respiratory TAU, GlaxoSmithKline
- David J. Flint
- Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde
- Susan Pyne
- Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde
- Anthony Habgood
- Respiratory Medicine NIHR Biomedical Research Centre, University of Nottingham
- Louise A. Organ
- Respiratory Medicine NIHR Biomedical Research Centre, University of Nottingham
- Chitra Joseph
- Respiratory Medicine NIHR Biomedical Research Centre, University of Nottingham
- Rochelle C. Edwards-Pritchard
- Respiratory Medicine NIHR Biomedical Research Centre, University of Nottingham
- Toby M. Maher
- NIHR Respiratory Clinical Research Facility, Royal Brompton Hospital
- Andrew J. Fisher
- Fibrosis Research Group, Newcastle University Biosciences Institute and Newcastle University Translational and Clinical Research Institute
- Natasja Stæhr Gudmann
- Nordic Bioscience A/S, Biomarkers and Research
- Diana J. Leeming
- Nordic Bioscience A/S, Biomarkers and Research
- Rachel C. Chambers
- Centre for Inflammation and Tissue Repair, University College London
- Pauline T. Lukey
- Fibrosis DPU, Respiratory TAU, GlaxoSmithKline
- Richard P. Marshall
- Fibrosis DPU, Respiratory TAU, GlaxoSmithKline
- Simon J. F. Macdonald
- Fibrosis DPU, Respiratory TAU, GlaxoSmithKline
- R. Gisli Jenkins
- Respiratory Medicine NIHR Biomedical Research Centre, University of Nottingham
- Robert J. Slack
- Fibrosis DPU, Respiratory TAU, GlaxoSmithKline
- DOI
- https://doi.org/10.1038/s41467-020-18397-6
- Journal volume & issue
-
Vol. 11,
no. 1
pp. 1 – 14
Abstract
The αvβ6 integrin is key in activating the pro-fibrotic cytokine TGFβ in idiopathic pulmonary fibrosis. Here, the authors show an inhaled small molecule αvβ6 inhibitor GSK3008348 induces prolonged inhibition of TGFβ signaling pathways in human and murine models of lung fibrosis via αvβ6 degradation.
