2. Academic Validation
  3. A Novel Potent Oral Series of VEGFR2 Inhibitors Abrogate Tumor Growth by Inhibiting Angiogenesis

A Novel Potent Oral Series of VEGFR2 Inhibitors Abrogate Tumor Growth by Inhibiting Angiogenesis

  • J Med Chem. 2016 Jan 14;59(1):132-46. doi: 10.1021/acs.jmedchem.5b01582.
Guido Bold 1,  Christian Schnell 1,  Pascal Furet 1,  Paul McSheehy 1,  Josef Brüggen 1,  Jürgen Mestan 1,  Paul W Manley 1,  Peter Drückes 1,  Marion Burglin 1,  Ursula Dürler 1,  Jacqueline Loretan 1,  Robert Reuter 1,  Markus Wartmann 1,  Andreas Theuer 1,  Beatrice Bauer-Probst 1,  Georg Martiny-Baron 1,  Peter Allegrini 1,  Arnaud Goepfert 1,  Jeanette Wood 1,  Amanda Littlewood-Evans 1
Affiliations

Affiliation

  • 1 Oncology Research, Novartis Institutes for BioMedical Research , 4002 Basel, Switzerland.
PMID: 26629594 DOI: 10.1021/acs.jmedchem.5b01582
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/KDR/Flk-1) tyrosine kinase inhibitors. In biochemical and cellular assays, the compounds exhibit single-digit nanomolar potency toward VEGFR2/KDR/Flk-1. 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.

Figures
Products