DW14383 is a potent, selective and irreversible inhibitor of FGFR1-4 with IC50 of <0.3 nM, 1.1 nM, <0.3 nM and 0.5 nM for FGFR1/2/3/4 respectively.
DW14383 displays >1100-fold selectivity for FGFR1 over recombinant KDR.
DW14383 is more potent than TAS-120 and comparable to AZD4547.
DW14383 (20 nM) completely inhibited FGFR4 phosphorylation and ERK phosphorylation in the Hep3B cells.
DW14383 inhibited the proliferation of FGFR-addicted cells by arresting cells at G1/S phase rather than apoptosis, selectively inhibited the BaF3/TEL-FGFR1 cell proliferation (IC50 < 0.2 nM).
DW14383 (25 mg/kg) effectively inhibited tumor growth in NCI-H1581 and Hep3B subcutaneous xenograft models, significantly suppressed FGFR signaling and inhibited tumor cell proliferation and angiogenesis in FGFR-dependent transplanted tumor tissues.
