FGF-R1 - SPR Binding Assay

Theoretical background: Fibroblast growth factor receptor (FGF-R) family consists of four genes encoding closely related transmembrane, tyrosine kinase receptors (termed FGF-R1 to FGF-R4). FGF bind in the presence of heparan sulfate proteoglucans (HSPG) to FGF-R forming a dimeric 2:2:2 FGF-FGFR-HSPG ternary complex on the cell surface. Complex formation induces receptor dimerization and a subsequent transphosphorylation of tyrosine residues in the activation loop of the kinase domain. Receptor activation regulates many key processes such as cell proliferation, survival, migration and differentiation by linking FGF-R to RAS / MAPK, PI3K / AKT and PKC pathways.

FGF-R1 and inhibitors: SU11652 (IC₅₀ = 170 nM [1]), SU11654, and SU11655 are indolinone based molecules specifically designed to inhibit VEGFR, PDGFR, FGFR, and c-KIT family members with different potency. PD173074, a cell-permeable pyridopyrimidine compound, is also an ATP competitive inhibitor selectively targets the tyrosine kinase domain of FGF and VEGF receptors (FGF-R1 IC₅₀ = 25 nM [2]). CHIR-258 / Dovitinib / TKI-258, a novel, multitargeted tyrosine kinase inhibitor (for FGF-R1, FGF-R3, VEGF-R1/2/3, PDGF-R, FLT3, c-KIT, and CSF-1R) is still in clinical trials (FGF-R1: IC₅₀ = 8 nM [3]).