FGFR

FGF (22 members) FGFs require heparan sulfate to activate their receptors FGFR Four members expressed as a number of splice variants Proliferation of many cell types. Embryo patterning and organogenesis, bone development, angiogenesis... 

More TKIs directed against other tyrosine kinases, like c-Met, IGF1R, Flt-3, FGFRs, Tie-2, Axl or Ron are at earlier stages of development with the most advanced candidates having entered phase II studies in different types of cancers. 

Schlessinger, J. et al., Crystal structure of a ternary FGF-FGFR-heparin complex reveals a dual role for heparin in FGFR binding and dimerization, Mol. Cell., 6, 743-750, 2000. 

The complexity of FGF action is compounded by the existence of at least four receptors for FGF (FGFR1-4). Three FGFRs are expressed in the CNS where they exist as... 

COX (i) cyclooxygenase (ii) cytochrome oxidase FGFR fibroblast growth factor receptor... 

BMS582664 is a dual inhibitor of VEGFR family and FGFR family kinases under development by Bristol-Myers Squibb (New York, NY, www.bms.com) as an orally-active compound for the potential treatment of cancer. Preclin-ical data on BMS582664 were presented at the 96th AACR meeting, April... 

Epidermal growth factor receptor (EGFR) Fibroblast growth factor receptor (FGFR) Vascular endothelial growth factor receptor (VEGFR)... 

Fig. 4 Interaction of basic FGF on heparan sulfate PG (1) and free GAG (2) induces FGFR dimerization, leading to tyrosine kinase (TK) activation and signal transduction.

Cebria, F., Kobayshi, C., Umesono, Y., Nakazawa, M., Mineta, K., Ikeo, K., Gojobori, T., Itoh, M., Tairi, M., Alvarado, A.S. and Agata, K. (2002) FGFR-related gene nou-darake restricts brain tissues to the head region of planarians. Nature 41 9, 620-624. 

Fig. 8. Paracrine and autocrine interactions of FGFR in prostatic cells.

With the exception of FGFR4, mRNA for all other three receptors have been reported to be present in the normal human prostate (13). In contrast to the prostatic stromal cells, which mainly secrete FGF7 and to a lesser extent FGF2 and FGF1, the epithelium cells do not produce any FGF. Flowever, both stromal and epithelial cells express FGFR isoforms (Fig. 8) and therefore it can be proposed that the... 

A. Kinase Growth Factor VEGFR-2 and FGFR-1 Inhibitors... 

Pyridin-2-yl-amino)-thiazol-5-yl-aminomethyl derivatives, (VII), prepared by Borzilleri (7) inhibited the tyrosine kinase activity of growth factor receptors of VEGFR-2 and FGFR-1 and were useful as antiangiogenic agents. 

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