tcsc5343 FIIN-2

FIIN-2 is an irreversible inhibitor of FGFR with an IC₅₀ of 3.1, 4.3, 27, and 45 nM for FGFR1, FGFR2, FGFR3 and FGFR4, respectively.

IC50 & Target: IC50: 3.1 nM (FGFR1), 4.3 nM (FGFR2), 27 nM (FGFR3), 45 nM (FGFR4)^[1]

In Vitro: FIIN-2 potently inhibits WT FGFRs (EC₅₀s in the 1- to 93-nM range) and the gatekeeper mutant of FGFR2 (EC₅₀ of 58 nM). FIIN-2 also moderately inhibits EGFR, with an IC₅₀ of 204 nM. FIIN-2 inhibits proliferation of FGFR1-4 Ba/F3 cells with EC₅₀s in the single- to double-digit nanomolar range and are especially potent against FGFR2, with EC₅₀s in the 1-nM range. FIIN-2 shows good potency against gatekeeper mutant V564F^[1].

In Vivo: Treatment of fish in the embryonic state with either FIIN-2 causes defects to the posterior mesoderm similar to the phenotypes reported following genetic knockdown of FGFR or treatment with other reported FGFR inhibitors. FIIN-2 causes mild or severe phenotypes to the tail morphogenesis in all treated embryonic zebrafish^[1].