Fibroblast growth factor receptor 1-3 kinase domains (FGFR1-3) (FGFR1-3)

The Fibroblast Growth Factor Receptor 1-3 (FGFR1-3) kinase domains are the intracellular enzymatic components of a subfamily of receptor tyrosine kinases that play critical roles in cellular signaling [1]. Upon binding of fibroblast growth factors (FGFs) to the extracellular domain, these kinase domains undergo trans-phosphorylation, initiating downstream cascades such as the MAPK/ERK, PI3K/AKT, and PLCγ pathways [2]. These pathways regulate essential biological processes including cell proliferation, differentiation, migration, and survival [3]. In many human malignancies, FGFR1, FGFR2, and FGFR3 are frequently dysregulated through gene amplifications, point mutations, or chromosomal translocations, leading to constitutive kinase activity and oncogenic transformation [4]. Consequently, the FGFR1-3 kinase domains have become significant therapeutic targets, particularly in urothelial carcinoma and cholangiocarcinoma [5]. Small molecule inhibitors, such as erdafitinib and pemigatinib, are designed to bind to the ATP-binding pocket of these kinase domains to block signaling [6]. However, therapeutic use is often limited by off-target effects like hyperphosphatemia, which results from the inhibition of FGF23 signaling in the kidney [7]. These inhibitors require careful monitoring of serum phosphate and ocular health due to the risk of retinal pigment epithelial detachment [8].

Other names

FGFR1FGFR2FGFR3CD331CD332CD333Tyrosine-protein kinase receptor 1Tyrosine-protein kinase receptor 2Tyrosine-protein kinase receptor 3

ATP-competitive inhibition of the intracellular tyrosine kinase domain