| BGJ398 is a potent and selective inhibitor of the FGFR family of tyrosine kinase receptors FGFR1, FGFR2, FGFR3, and FGFR4 with IC50s of 0.9, 1.4, 1 and 60 nM, respectively. BGJ398 also inhibits VEGFR2 with an IC50 value of 180 nM. In addition, BGJ398 prevents another panel of kinases including ABL, FYN, KIT, LCK, LYN and YES with IC50 values of 2.3, 1.9, 0.75, 2.5, 0.3 and 1.1 µM, respectively. In vitro, BGJ398 inhibits the proliferation of the FGFR1-, FGFR2-Q, FGFR3- and FGFR3-Q dependent BaF3 cells with IC50 values of 2.9, 2, 2 and 0.7 nM, respectively. BGJ398 suppresses proliferation of the bladder cancer cell lines overexpressing WT FGFR3 (including RT112, RT4, SW780 and JMSU1) with IC50 values ranging from 5 to 32 nM.[1] Moreover, cancer cell lines harboring FGF19 copy number gain at the 11q13 amplicon are sensitive to BGJ398 only when concomitant expression of β-klotho occurs.[2] In the human bladder cancer cell line RT112 xenograft model in athymic Nude-nu mice, BGJ398 (10 and 30 mg/kg) induces significant tumor growth inhibition and stasis. Furthermore, in an agar chamber model in vivo, BGJ398 (10, 30, and 50 mg/kg) significantly inhibits bFGF-stimulated angiogenesis in a dose-dependent manner.[1] |
