FIIN-3 is an irreversible inhibitor of FGFR with an IC₅₀ of 13.1, 21, 31.4, and 35.3 nM for FGFR1, FGFR2, FGFR3 and FGFR4, respectively.

FIIN-3 potently inhibits both WT FGFRs (EC₅₀ in the 1- to 41-nM range) and the gatekeeper mutant of FGFR2 (EC₅₀ of 64 nM). FIIN-3 also strongly inhibits EGFR, with an EC₅₀ of 43 nM. FIIN-3 shows good potency against gatekeeper mutant V564F; FIIN-3 also is potent against the gatekeeper-plus-1 mutant E565K; FIIN-3 also displays antiproliferative activity (with an EC₅₀ of 135 nM) against Ba/F3 cells transformed by the EGFR vIII fusion protein, which has a WT EGFR kinase domain. FIIN-3 shows even better activity against EGFR mutant L858R (EC₅₀ of 17 nM) and moderate activity, displaying an EC₅₀ of 231 nM, against the EGFR mutant L858R/T790M mutant. In WT FGFR2 Ba/F3 cells, FIIN-3 completely inhibits the FGFR2 autophosphorylation on Tyr656/657 at concentrations as low as 3 nM. In FGFR2 V564M Ba/F3 cells, FIIN-3 is capable of inhibiting the FGFR2 mutant V564M autophosphorylation with partial inhibition at 100 nM and complete inhibition observed at 300 nM^[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

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• [1]. Tan L et al. Development of covalent inhibitors that can overcome resistance to first-generation FGFR kinase inhibitors. Proc Natl Acad Sci U S A, 2014 Nov 11, 111(45):E4869-77  [Content Brief]