Erdafitinib

Erdafitinib (JNJ-42756493) is a potent and orally available FGFR family inhibitor; inhibits FGFR1/2/3/4 with IC₅₀s of 1.2, 2.5, 3.0 and 5.7 nM, respectively. IC50 & Target: IC50: 1.2 nM (FGFR1), 2.5 nM (FGFR2), 3.0 nM (FGFR3)and 5.7 nM (FGFR4)^[1] In Vitro: Erdafitinib (JNJ-42756493) inhibits the tyrosine kinase activities of FGFR1-4 in time-resolved fluorescence assays with IC₅₀ values of 1.2, 2.5, 3.0 and 5.7 nM, respectively. The closely related VEGFR2 kinase is less potently inhibited (30-fold less potent compared to FGFR1) by erdafitinib, with an IC₅₀ value of 36.8 nM. Erdafitinib binds FGFR1, 3, 4, and 2 with K_d values of 0.24, 1.1, 1.4 and 2.2 nM, respectively. The K_d value for VEGFR2 is higher at 6.6 nM. Erdafitinib inhibits proliferation of FGFR1, 3, and 4 expressing cells with IC₅₀ values of 22.1, 13.2, and 25nM, respectively^[1]. In Vivo: In xenografts from human tumor cell lines or patient-derived tumor tissue with activating FGFR alterations, Erdafitinib administration results in potent and dose-dependent antitumor activity accompanied by pharmacodynamic modulation of phospho-FGFR and phospho-ERK in tumors^[1].