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

Fibroblast growth factor receptor 1 (FGFR1) and fibroblast growth factor receptor 3 (FGFR3) are members of the receptor tyrosine kinase family that play pivotal roles in cell signaling, growth, and development (UniProt P11362, P22607). These transmembrane proteins are activated by the binding of fibroblast growth factors (FGFs), leading to receptor dimerization and the activation of downstream pathways such as MAPK/ERK and PI3K/AKT (PubMed: 25762551). FGFR1 is notably involved in metabolic regulation and is frequently amplified in breast and lung cancers, while FGFR3 is a key regulator of bone growth and is often mutated or fused in urothelial carcinomas (PubMed: 31557481). Beyond oncology, FGFR3 mutations are the primary cause of skeletal dysplasias, most notably achondroplasia (NIH: MedlinePlus). In the pharmaceutical industry, these kinases are primary targets for small-molecule inhibitors like erdafitinib and pemigatinib, which are designed to block the ATP-binding site of the kinase domain (FDA: Balversa, Pemazyre). Clinical management of patients on these therapies involves monitoring for specific genetic alterations and managing class-wide side effects, particularly hyperphosphatemia, which arises from the inhibition of FGFR1-mediated phosphate handling in the kidneys (PubMed: 29153091). Other significant safety concerns include ocular toxicities such as central serous retinopathy and dermatologic effects like hand-foot syndrome (FDA: Lytgobi Label). The development of selective and irreversible inhibitors continues to be a major focus to overcome resistance mutations in the kinase domain (PubMed: 33076159).

Other names

CD331CD333FLT2CEK1BFGFRACHJTK4HBGLHBGFR

ATP-competitive inhibition of the intracellular tyrosine kinase domain