FGF-R1 - SPR Binding Assay

Our service for comprehensive kinetic characterization of your small molecule kinase inhibitors

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]). 

Figure: Real-time kinetic analysis of kinase inhibitor R-406 binding to FGF-R1 using surface plasmon resonance.

 

[1] Liao AT et al. (2002) Blood. 15;100(2):585-93.
[2] Mohammadi M et al. (1998) EMBO J. 1998 Oct 15;17(20):5896-904.
[3] Trudel S et al. (2005) Blood. 1;105(7):2941-8.

 

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