ASP5878

ASP5878 is an inhibitor of wild-type FGFR1, -2, -3, and -4 (IC₅₀s = 0.47, 0.6, 0.74, and 3.5 nM, respectively) and mutant FGFR3^K650E, FGFR3^K560M, and FGFR4^N535K (IC₅₀s = 1.6, 4.2, and 78 nM, respectively).¹ It is selective for these FGFRs over a panel of 128 additional kinases at 200 nM but does inhibit VEGFR2 and CSF-1 receptor tyrosine kinase (FMS; IC₅₀s = 25 and 150 nM, respectively). It selectively inhibits the proliferation of urothelial cancer cell lines with FGFR gene alterations (IC₅₀s = <100 nM) over those without FGFR gene alterations (IC₅₀s = ≥300 nM). ASP5878 also inhibits the proliferation of adriamycin-resistant UM-UC-14 bladder cancer cells and gemcitabine-resistant RT-112 bladder cancer cells (IC₅₀s = 11 and 10 nM, respectively). In vivo, ASP5878 (3 mg/kg) induces tumor regression in a UM-UC-14 mouse xenograft model. It also increases femur and tibia length and femur growth plate cartilage thickness in Fgfr3^G380R male mice in a model of achondroplasia when administered at a dose of 300 µg/kg.²

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1. Kikuchi, A., Suzuki, T., Nakazawa, T., et al. ASP5878, a selective FGFR inhibitor, to treat FGFR3-dependent urothelial cancer with or without chemoresistance. Cancer Sci. 108(2), 236-242 (2017).

2. Ozaki, T., Kawamoto, T., Iimori, Y., et al. Evaluation of FGFR inhibitor ASP5878 as a drug candidate for achondroplasia. Sci. Rep. 10(1), 20915 (2020).