Fig. 1

Strategies to overcome mutation-based FGFR-TKI resistance. a The binding site of LY2874455 is far away from gatekeeper residue L550 of FGFR4 (PDB: 5XFF). b Ponatinib binds to the FGFR kinase in an inactive and DFG-out conformation (PDB: 4V01). c FIIN-3 covalent binds the C477 of P-loop to overcome FGFR gatekeeper mutation-induced resistance (PDB: 4R6V). d FGF401 covalently binds residue C552 of Hinge to specific overcome the FGFR4 gatekeeper mutation (PDB: 6JPJ). Kinases are shown as cartoons, TKIs are shown in grey sticks, gatekeeper residues are shown in blue sticks, DFG motifs are shown in yellow sticks, and covalently bound cysteine is shown in brown sticks