Basic fibroblast growth factor (FGF), also known as bFGF and FGF2, is a member of the fibroblast growth factor family. There are two inhibitors which affect the actions of FGF2: PD 173074 and SU 5402. PD 173074 is an inhibitor of FGFR1. It can potently and selectively antagonize the neurotrophic and neurotropic actions of FGF-2. Nanomolar concentrations of PD 173074 preventes FGF2, but not insulin-like growth factor-1, support of cerebellar granule neuron survival under conditions of serum/K(+) deprivation. As an inhibitor of FGF2, SU 5402 is effective only at a 1,000-fold greater concentration. PD 173074 and SU 5402 show 1,000-fold differential IC(50) values for inhibition of FGF2-stimulated neurite outgrowth in PC12 cells and in granule neurons, and FGF2-induced mitogen-activated protein kinase (p44/42) phosphorylation. The two inhibitors fail to disturb downstream signalling stimuli of FGF2. PD 173074 represents a valuable tool for dissecting the role of FGF2 in normal and pathological nervous system function without compromising the actions of other neurotrophic factors.
Fibroblast growth factor receptors are receptors that bind to members of the fibroblast growth factor family of proteins. The fibroblast growth factor (FGF)/fibroblast growth factor receptor (FGFR) signaling network plays an important role in cell growth, survival, differentiation, and angiogenesis. Deregulation of FGFR signaling can lead to cancer development. SSR128129E (SSR) is an FGFR inhibitor that binds to the extracellular part of the receptor. SSR does not compete with FGF for binding to FGFR but inhibits FGF-induced signaling linked to FGFR internalization in an allosteric manner. SSR is a small molecule allosteric inhibitor of FGF/FGFR signaling, acting via binding to the extracellular part of the FGFR.