[CAS NO. 1234356-69-4]  Derazantinib(ARQ-087)

ARQ-087 has anti-proliferative activity in cell lines driven by FGFR dysregulation, including amplifications, fusions, and mutations. Cell cycle studies in cell lines with high levels of FGFR2 protein show a positive relationship between ARQ 087 induced G1 cell cycle arrest and subsequent induction of apoptosis. ARQ 087 inhibits the auto-phosphorylation of FGFR1 and FGFR2 in a dose-dependent manner. In Cos-1 cells overexpressing full-length FGFR1, FGFR2, FGFR3 and FGFR4, ARQ 087 inhibits their phosphorylation with EC50 values of < 0.123 μM, 0.185 μM, 0.463 μM, >10 μM respectively. ARQ 087 inhibits FGFR kinase by an ATP competitive mechanism, and is capable of inhibiting both the inactive and fully active forms of the FGFR kinase. Hence, ARQ 087 delays FGFR activation by inhibiting its autophosphorylation, as well as inhibition of the phosphorylated active kinase.