PD173074

PD173074 is a potent FGFR1 inhibitor with an IC₅₀ of 25 nM and also inhibits VEGFR2 with an IC₅₀ of 100-200 nM, showing 1000-fold selectivity for FGFR1 over PDGFR and c-Src. IC50 & Target: IC50: 25 nM (FGFR1), 100-200 nM (VEGFR2) In Vitro: PD 173074 inhibits autophosphorylation of FGFR1 in a dose-dependent manner with an IC₅₀ in the range 1-5 nM. PD 173074 is an ATP-competitive inhibitor of FGFR1 with an inhibitory constant (K_i) of 40 nM^[1]. PD 173074 and SU 5402 produce concentration-dependent reductions in FGF-2 enhancement of granule neuron survival, with IC₅₀ values of 8 nM and 9 μM, respectively. PD 173074 does not inhibit neurotrophic and neuritogenic actions of FGF-2 signalling molecules in cerebellar granule neurons. PD 173074 and SU 5402 concentration-dependently inhibits the neurite growth response, when tested on FGF-2-treated granule neurons growing on polylysine/laminin, with IC₅₀s of 22 nM and 25 μM, respectively^[2]. PD173074 effectively antagonizes the effect of FGF-2 on proliferation and differentiation of OL progenitors in culture. Mitogen-activated protein kinase (MAPK) activation, a downstream event after activation of either FGFR or PDGFR, is also blocked by PD173074 in OL progenitors stimulated with FGF-2 but not PDGF^[3]. In Vivo: PD 173074 (1 mg/kg, i.p.) exhibits dose-dependent inhibition of FGF-induced neovascularization and angiogenesis in mice^[1]. D173074 (25 mg/kg, p.o.) significantly inhibits tumor growth in mice^[4].