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A novel potent oral series of VEGFR2 inhibitors abrogate tumor growth by inhibiting angiogenesis

Bold, Guido, Schnell, Christian, Mcsheehy, Paul M.J., Brueggen, Josef, Mestan, Juergen, Manley, Paul W., Drueckes, Peter, Burglin, Marion, Duerler, Ursula, Loretan, Jacqueline, Reuter, Robert, Wartmann, Markus, Theuer, Andreas, Bauer-Probst, Beatrice, Martiny-Baron, Georg, Allegrini, Peter Roland, Furet, Pascal, Wood, Jeanette, Littlewood-Evans, Amanda and Goepfert, Arnaud (2015) A novel potent oral series of VEGFR2 inhibitors abrogate tumor growth by inhibiting angiogenesis. Journal of medicinal chemistry, 59 (1). pp. 132-146. ISSN 0022-26231520-4804


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 vasculature as demonstrated by ELISA for TIE-2 in lysates, or by immunohistochemical analysis. This novel series of compounds shows potential for the treatment of solid tumors and other diseases where angiogenesis plays an important role.

Item Type: Article
Date Deposited: 23 Dec 2015 00:45
Last Modified: 04 Jul 2016 23:45


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