A number of profibrotic mediators including platelet-derived growth factor (PDGF), fibroblast growth factor (FGF) and transforming growth factor- are believed to play important roles in the pathogenesis of IPF. interferes with processes active in fibrosis, fibroblast proliferation, migration and differentiation http://ow.ly/Iae9z Introduction Nintedanib (international non-proprietary name), formerly known by its development code BIBF 1120, is a small molecule that was originally designed as an ATP-competitive inhibitor of fibroblast growth factor receptor (FGFR)-1 and vascular endothelial growth factor receptor (VEGFR)-2. Both these receptors are pro-angiogenic receptor tyrosine kinases and nintedanib was designed as Peramivir trihydrate an anti-angiogenic drug for cancer indications. The clinical development of Peramivir trihydrate nintedanib for cancer indications, including nonsmall cell lung cancer, colorectal cancer and ovarian cancer, is ongoing. As nintedanib is also an inhibitor of platelet-derived growth factor receptor (PDGFR)- and , it was selected for development as a potential treatment for idiopathic pulmonary fibrosis (IPF). The fact that the pathobiology of IPF shows several striking similarities and links to cancer biology (reviewed in [1]) also supports the rationale for the exploration of nintedanib in IPF. In the two replicate phase III INPULSIS? studies [2], nintedanib was shown to slow disease progression in patients with IPF by reducing the annual rate of decline in forced vital capacity (FVC) [3]. This review summarises the current understanding of the mode of action of nintedanib in fibrotic lung diseases like IPF. The roles Rabbit polyclonal to ACC1.ACC1 a subunit of acetyl-CoA carboxylase (ACC), a multifunctional enzyme system.Catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the rate-limiting step in fatty acid synthesis.Phosphorylation by AMPK or PKA inhibits the enzymatic activity of ACC.ACC-alpha is the predominant isoform in liver, adipocyte and mammary gland.ACC-beta is the major isoform in skeletal muscle and heart.Phosphorylation regulates its activity. of the main target receptor tyrosine kinases of nintedanib in IPF are explained. experiments with primary lung fibroblasts from patients with IPF and from control donors, and studies in animal models of lung fibrosis, are summarised. Taken together, these studies demonstrate the potent anti-fibrotic and anti-inflammatory activities of nintedanib. These features may explain the slowing of disease progression demonstrated in patients with IPF treated with nintedanib. Idiopathic pulmonary fibrosis IPF is a devastating and disabling progressive lung disease associated with a median survival of only 2C3?years after diagnosis [4]. IPF is the most common form of the idiopathic interstitial pneumonias [5], with an incidence ranging between 0.22 and 17.4 per 100?000 population depending on the case definition, the region and the methodology used [6]. IPF usually presents in the sixth or seventh decade of life and occurs more frequently in men than in women [4, 7]. In international guidelines for the management of IPF, published in 2011 [4], the treatment options that were Peramivir trihydrate strongly recommended were limited to oxygen supplementation and lung transplantation. Despite high medical need, these guidelines did not recommend any specific pharmacological therapy for the chronic treatment of IPF [4]. Pirfenidone was introduced to the market for the treatment of IPF in Japan in 2008 and, based on the results of two phase III clinical trials (CAPACITY-1 and 2) [8], was later Peramivir trihydrate launched in several countries and regions including Europe, Canada, South Korea, China, India, Mexico and Argentina. An additional phase III study (ASCEND) was requested to support its regulatory registration in the USA and the positive results of this trial have recently been published [9]. With the publication of the phase III clinical results on the efficacy and safety of nintedanib in IPF (INPULSIS?-1 and INPULSIS?-2) [3] and the recent approval of both pirfenidone and nintedanib for the treatment of IPF by the US Food and Drug Administration, physicians will soon have a choice of treatments for IPF after more than a decade of disappointment and failed clinical trials. The pathology of IPF is characterised by repetitive microscopic alveolar epithelial cell injury and dysregulated repair, fibrosis and excessive deposition of extracellular matrix (ECM), resulting in loss of.