Table 1.

The FGFR2 p.E565A and p.L617M mutations confer resistance to infigratinib and other FGFR inhibitors.

IC50 (nmol/L) values
InfigratinibAZD4547ErdafitinibTAS120PonatinibDovitinib
NIH3T3FK WT1 (18.24)1 (36.22)1 (5.16)1 (6.89)1 (54.83)1 (489.78)
FK p.E565A27 (490.91)42 (1,510.08)20 (105.68)5 (32.14)0.36 (19.72)4 (1,936.42)
FK p.L617M126 (2,296.15)59 (2,152.78)28 (144.88)0.177 (1.22)14 (762.08)3 (1,674.94)
293TFK WT1 (4.04)1 (7.80)1 (0.52)1 (1.35)1 (9.57)1 (161.81)
FK p.E565A44 (176.39)84 (656.15)65 (33.65)11 (14.32)0.48 (4.55)8 (1,253.14)
FK p.L617M12 (48.98)10 (76.74)31 (15.96)3 (4.59)0.40 (3.87)6 (990.83)
MMNK-1FK WT1 (44.98)1 (4.08)1 (0.66)1 (0.20)1 (22.59)1 (77,983.01)
FK p.E565A578 (26,001.60)257 (1,049.54)15 (10)Ambiguous (>5,000)17 (387.26)0.03 (2,344.23)
FK p.L617M213 (9,594.01)3 (10.69)17 (10.94)4 (0.74)2 (44.16)2151 (>5,000)
  • Note: Bold numbers represent fold change of inhibitor concentrations relative to FK WT. Nanomolar IC50 values are listed in parentheses for each inhibitor and condition. Values represent mean ± SEM of three independent experiments with six replicates per condition.