tcsc5504 CH5183284

CH5183284 is an orally available and selective FGFR inhibitor with IC₅₀s of 9.3, 7.6, and 22 nM for FGFR1, FGFR2, FGFR3, and FGFR4, respectively.

IC50 & Target: IC50: 9.3 nM (FGFR1), 7.6 nM (FGFR2), 22 nM (FGFR3), 290 nM (FGFR4)^[1]

In Vitro: CH5183284 is well balanced in cellular antiproliferative activity against SNU-16 and stability in human liver microsome. The selectivity of 8 to inhibit FGFR over KDR is suggested to be caused by the difference in the interaction with M535 in FGFR1 and L889 in KDR^[1]. The IC₅₀ of CH5183284/Debio 1347 is 29 nM for FGF-dependent proliferation and 780 nM for VEGF-dependent proliferation^[2].

In Vivo: CH5183284 treatment shows a dose-dependent tumor regression (tumor growth inhibition (TGI)=106% at 30 mg/kg and 147% at 100 mg/kg) without apparent body weight loss. CH5183284 treatment also shows significant in vivo efficacy in xenograft mice models with FGFR genetic alterations, such as KG1 (leukemia, FGFR1OP-FGFR1 fusion), MFE280 (endometrial cancer, FGFR2 S252W mutation), UM-UC-14 (bladder cancer, FGFR3 S249C mutation), and RT112/84 (bladder cancer, FGFR3-TACC3 fusion)^[1].