Document Report Card
Basic Information
ID: ALA5252510
Journal: J Med Chem
Title: A Novel Potent Oral Series of VEGFR2 Inhibitors Abrogate Tumor Growth by Inhibiting Angiogenesis.
Authors: Bold G, Schnell C, Furet P, McSheehy P, Brüggen J, Mestan J, Manley PW, Drückes P, Burglin M, Dürler U, Loretan J, Reuter R, Wartmann M, Theuer A, Bauer-Probst B, Martiny-Baron G, Allegrini P, Goepfert A, Wood J, Littlewood-Evans A.
Abstract: This paper describes the identification of 6-(pyrimidin-4-yloxy)-naphthalene-1-carboxamides as a new class of potent and selective human vascular endothelial growth factor receptor 2 (VEGFR2) tyrosine kinase inhibitors. In biochemical and cellular assays, the compounds exhibit single-digit nanomolar potency toward VEGFR2. Compounds of this series show good exposure in rodents when dosed orally. They potently inhibit VEGF-driven angiogenesis in a chamber model and rodent tumor models at daily doses of less than 3 mg/kg by targeting the tumor vasculature as demonstrated by ELISA for TIE-2 in lysates or by immunohistochemical analysis. This novel series of compounds shows a potential for the treatment of solid tumors and other diseases where angiogenesis plays an important role.
CiteXplore: 26629594