Intedanib, a triple kinase inhibitor of VEGFR, FGFR and PDGFR for the treatment of cancer and idiopathic pulmonary fibrosis.
Tyrosine kinase receptors have important signaling functions in various physiological and pathological pathways. The recognition of their involvement in tumor angiogenesis, which is the main event of tumor progression, opened a new era in the discovery of anticancer drugs. Developers soon grasped that by targeting several tyrosine kinase receptors at once, so-called multitarget tyrosine kinase inhibitors, a drug could dramatically affect the progression of cancer and decrease resistance. Several antiangiogenic, multitarget tyrosine kinase inhibitors, such as sorafenib and sunitinib, are already marketed, while many more are undergoing clinical trials for a range of cancer types. Boehringer Ingelheim Corp is developing intedanib (BIBF-1120), a triple kinase inhibitor blocking VEGFR, PDGFR and FGFR for the treatment of several malignancies and idiopathic pulmonary fibrosis. The preliminary data for intedanib appears at least as good as that for other antiangiogenic tyrosine kinase inhibitors or other antiangiogenic approaches that are not targeting the tyrosine kinases. The sustained inhibition of VEGFR phosphorylation (> 24 h), the fast in vivo clearance and clinical efficacy against a broad range of malignancies appear to be the major advantages of intedanib. Furthermore, the existing data suggest an excellent safety profile. At the time of publication, intedanib had reached phase III trials for the treatment of NSCLC and ovarian cancer.
Antoniu
Sabina A
SA
University of Medicine and Pharmacy, Gr.T.Popa Iasi, Faculty of Medicine, Department Medicine II-Pulmonary Disease, Pulmonary Disease University Hospital, 30 Dr I Cihac Street, Iasi 700115, Romania. sabina.antonela.antoniu@pneum.umfiasi.ro
Kolb
Martin R J
MR
D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D016503:Drug Delivery Systems; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000188:drug therapy / Q000503:physiopathology; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D017468:Receptors, Fibroblast Growth Factor / Q000037:antagonists & inhibitors; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors
D020533:Angiogenesis Inhibitors; D007211:Indoles; D047428:Protein Kinase Inhibitors; D017468:Receptors, Fibroblast Growth Factor; D017479:Receptors, Platelet-Derived Growth Factor; D040262:Receptors, Vascular Endothelial Growth Factor; C530716:nintedanib