Fibroblast growth factor receptor 1 and fibroblast growth factor receptor 3 (FGFR1/FGFR3)

Fibroblast growth factor receptor 1 and fibroblast growth factor receptor 3 are highly conserved, transmembrane receptor tyrosine kinases belonging to the FGFR family. They are composed of an extracellular ligand-binding domain (with three immunoglobulin-like subdomains), a single transmembrane helix, and an intracellular tyrosine kinase domain. FGFR1 and FGFR3 bind fibroblast growth factors (FGFs) and initiate intracellular signaling cascades that regulate cell proliferation, differentiation, survival, angiogenesis, wound healing, bone growth, and metabolic processes. Genetic alterations—such as activating mutations, fusions, or gene amplification—in these receptors can drive cancer or developmental diseases and are therapeutically actionable with selective small molecule inhibitors. FGFR1 and FGFR3 are well-validated therapeutic targets in several cancer types (notably urothelial carcinoma) and are being actively investigated as predictive biomarkers and drug targets in numerous other diseases.

Other names

Basic fibroblast growth factor receptor 1fms-related tyrosine kinase-2CD331Pfeiffer syndrome proteinCD333fms-related tyrosine kinase 3Achondroplasia proteinFGFR-3

Competitive inhibition of the ATP-binding site of FGFR1 or FGFR3 kinase domains, thus blocking FGF-mediated receptor phosphorylation and downstream signaling. Inhibition of downstream pathways, including RAS-MAPK, PI3K-AKT, and PLCγ, to suppress proliferation and induce apoptosis in tumor cells with FGFR alterations.