title: Nintedanib: from discovery to the clinic.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry; §Department of Drug Metabolism and Pharmacokinetics; ‡Department of Non-Clinical Drug Safety; ∥Department of Translational Medicine and Clinical Pharmacology; ⊥Department of Respiratory Diseases Research; and #Corporate Division Medicine, TA Oncology, Boehringer Ingelheim Pharma GmbH & Co. KG , 88397 Biberach an der Riss, Germany.
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Roth
authors.forename: Rudolf
authors.initials: R
authors.lastname: Binder
authors.forename: Florian
authors.initials: F
authors.lastname: Colbatzky
authors.forename: Claudia
authors.initials: C
authors.lastname: Dallinger
authors.forename: Rozsa
authors.initials: R
authors.lastname: Schlenker-Herceg
authors.forename: Frank
authors.initials: F
authors.lastname: Hilberg
authors.forename: Stefan-Lutz
authors.initials: SL
authors.lastname: Wollin
authors.forename: Rolf
authors.initials: R
authors.lastname: Kaiser
mesh_terms: D000818:Animals; D055808:Drug Discovery; D005260:Female; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000188:drug therapy*; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D007211:Indoles; D047428:Protein Kinase Inhibitors; C530716:nintedanib