RT Journal Article
SR Electronic
T1 Mode of action of nintedanib in the treatment of idiopathic pulmonary fibrosis
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 1434
OP 1445
DO 10.1183/09031936.00174914
VO 45
IS 5
A1 Lutz Wollin
A1 Eva Wex
A1 Alexander Pautsch
A1 Gisela Schnapp
A1 Katrin E. Hostettler
A1 Susanne Stowasser
A1 Martin Kolb
YR 2015
UL http://erj.ersjournals.com/content/45/5/1434.abstract
AB Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal disease characterised by fibrosis of the lung parenchyma and loss of lung function. Although the pathogenic pathways involved in IPF have not been fully elucidated, IPF is believed to be caused by repetitive alveolar epithelial cell injury and dysregulated repair, in which there is uncontrolled proliferation of lung fibroblasts and differentiation of fibroblasts into myofibroblasts, which excessively deposit extracellular matrix (ECM) proteins in the interstitial space. A number of profibrotic mediators including platelet-derived growth factor (PDGF), fibroblast growth factor (FGF) and transforming growth factor-β are believed to play important roles in the pathogenesis of IPF. Nintedanib is a potent small molecule inhibitor of the receptor tyrosine kinases PDGF receptor, FGF receptor and vascular endothelial growth factor receptor. Data from in vitro studies have shown that nintedanib interferes with processes active in fibrosis such as fibroblast proliferation, migration and differentiation, and the secretion of ECM. In addition, nintedanib has shown consistent anti-fibrotic and anti-inflammatory activity in animal models of lung fibrosis. These data provide a strong rationale for the clinical efficacy of nintedanib in patients with IPF, which has recently been demonstrated in phase III clinical trials. Nintedanib interferes with processes active in fibrosis, e.g. fibroblast proliferation, migration and differentiation http://ow.ly/Iae9z