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Potent, Selective Inhibitors of Fibroblast Growth Factor Receptor Define Fibroblast Growth Factor Dependence in Preclinical Cancer Models

Lookup NU author(s): Michael Batey, Professor Julie Irving, Professor Herbie Newell

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Abstract

We describe here the identification and characterization of 2 novel inhibitors of the fibroblast growth factor receptor (FGFR) family of receptor tyrosine kinases. The compounds exhibit selective inhibition of FGFR over the closely related VEGFR2 receptor in cell lines and in vivo. The pharmacologic profile of these inhibitors was defined using a panel of human tumor cell lines characterized for specific mutations, amplifications, or translocations known to activate one of the four FGFR receptor isoforms. This pharmacology defines a profile for inhibitors that are likely to be of use in clinical settings in disease types where FGFR is shown to play an important role. Mol Cancer Ther; 10(9); 1542-52. (C)2011 AACR.


Publication metadata

Author(s): Squires M, Ward G, Saxty G, Berdini V, Cleasby A, King P, Angibaud P, Perera T, Fazal L, Ross D, Jones CG, Madin A, Benning RK, Vickerstaffe E, O'Brien A, Frederickson M, Reader M, Hamlett C, Batey MA, Rich S, Carr M, Miller D, Feltell R, Thiru A, Bethell S, Devine LA, Graham BL, Pike A, Cosme J, Lewis EJ, Freyne E, Lyons J, Irving J, Murray C, Newell DR, Thompson NT

Publication type: Article

Publication status: Published

Journal: Molecular Cancer Therapeutics

Year: 2011

Volume: 10

Issue: 9

Pages: 1542-1552

Print publication date: 01/09/2011

Online publication date: 15/07/2011

Acceptance date: 21/06/2011

ISSN (print): 1535-7163

ISSN (electronic): 1538-8514

Publisher: American Association for Cancer Research

URL: http://dx.doi.org/10.1158/1535-7163.MCT-11-0426

DOI: 10.1158/1535-7163.MCT-11-0426


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