Nintedanib: from discovery to the clinic

J Med Chem. 2015 Feb 12;58(3):1053-63. doi: 10.1021/jm501562a. Epub 2015 Jan 14.


Nintedanib (BIBF1120) is a potent, oral, small-molecule tyrosine kinase inhibitor, also known as a triple angiokinase inhibitor, inhibiting three major signaling pathways involved in angiogenesis. Nintedanib targets proangiogenic and pro-fibrotic pathways mediated by the VEGFR family, the fibroblast growth factor receptor (FGFR) family, the platelet-derived growth factor receptor (PDGFR) family, as well as Src and Flt-3 kinases. The compound was identified during a lead optimization program for small-molecule inhibitors of angiogenesis and has since undergone extensive clinical investigation for the treatment of various solid tumors, and in patients with the debilitating lung disease idiopathic pulmonary fibrosis (IPF). Recent clinical evidence from phase III studies has shown that nintedanib has significant efficacy in the treatment of NSCLC, ovarian cancer, and IPF. This review article provides a comprehensive summary of the preclinical and clinical research and development of nintedanib from the initial drug discovery process to the latest available clinical trial data.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Discovery*
  • Female
  • Humans
  • Idiopathic Pulmonary Fibrosis / drug therapy*
  • Indoles / chemical synthesis
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Indoles / therapeutic use*
  • Neovascularization, Pathologic / drug therapy*
  • Ovarian Neoplasms / drug therapy*
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinase Inhibitors / therapeutic use


  • Indoles
  • Protein Kinase Inhibitors
  • nintedanib