Inhibitors of the fibroblast growth factor receptor

Abstract

Signaling through the fibroblast growth factor receptor (FGFR) tyrosine kinase is crucial to a number of key pharmacological processes; however, dysregulation of this signaling is observed with a number of different cancers suggesting that inhibition of FGFR may provide an important therapeutic agent in the treatment of cancers. This chapter provides an overview of the development of FGFR inhibitors beginning with the identification of nonselective FGFR inhibitors, then describing the medicinal chemistry optimization resulting in the delivery of a number of highly selective FGFR inhibitors, some of which are currently being assessed in clinical trials. The development of isoform selective FGFR inhibitors as well as covalent inhibitors and inhibitors of the inactive form of FGFR are also described.