Fibroblast growth factor receptors (FGFRs) are involved in cell proliferation, migration, differentiation, and survival. Erdafitinib is an orally bioavailable, small molecule inhibitor of FGFRs with IC50 values of 1.2, 2.5, 3.0, and 5.7 nM for FGFR1, 2, 3, and 4, respectively. It also shows potent inhibitory activity against VEGFR2 kinase with an IC50 value of 36.8 nM. Erdafitinib binds to FGFR1, 2, 3, and 4 with Kd values of 0.24, 2.2, 1.1, and 1.4 nM, respectively. It inhibited the proliferation of cells expressing FGFR1, 3, and 4 with IC50 values of 22.1, 13.2, and 25 nM, respectively. It showed inhibitory activity against BaF3 cells expressing VEGFR2 with an IC50 value of 1.16 μM. Erdafitinib at 100 nM inhibited pFGFR1, pFGFR3, and pFGFR4 in NCI-H1581, KMS-11, and MDA-MB-453 cells, respectively, and pFGFR2 L in SNU-16 cells at a concentration of 30 nM. In mice bearing xenograft tumors derived from SNU-16 gastric cancer cells harboring FGFR2 amplifications, the administration of erdafitinib (10 and 30 mg/kg) for 1 h significantly inhibited FGFR signaling and this effect maintained until 7- and 16-h post-treatment. The treatment of SNU-16 tumor-bearing mice with erdafitinib (10 and 30 mg/kg) for 21 days resulted in tumor growth inhibition of 37.8% and 59.4%, respectively, compared to the vehicle-treated animals[3].
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