Table 2.

AMG 925 activity in Ba/F3 cells expressing various FLT3 mutants

FLT3 mutationsIC50 (μmol/L)
Cell proliferation inhibitionP-STAT5 inhibition
AMG 925AC220SorafenibAMG 925AC220Sorafenib
Parental Ba/F3a0.308 ± 0.011>1>1>1>1>1
ITD0.014 ± 0.0010.001 ± 0.00030.006 ± 0.0010.014 ± 0.0010.001 ± 0.00030.005 ± 0.001
ITD/D835Y0.011 ± 0.0010.038 ± 0.0030.362 ± 0.0190.011 ± 0.0010.033 ± 0.0020.135 ± 0.003
ITD/F691I0.142 ± 0.0110.163 ± 0.0090.416 ± 0.0110.171 ± 0.0090.077 ± 0.0070.195 ± 0.007
ITD/Y842N0.009 ± 0.0010.030 ± 0.0080.341 ± 0.0130.007 ± 0.0010.037 ± 0.0030.132 ± 0.004
ITD/N676K0.018 ± 0.0020.028 ± 0.0020.201 ± 0.0130.008 ± 0.0010.030 ± 0.0020.104 ± 0.009
D835Y0.014 ± 0.0010.033 ± 0.0030.480 ± 0.0120.022 ± 0.0020.058 ± 0.0020.148 ± 0.004

NOTE: Cell proliferation was determined by CellTiter-Glo assay, P-STAT5 by MSD assay. IC50 values indicated as mean ± SD.

  • aGrowth of parental Ba/F3 cells is dependent on IL3. Ba/F3 derivatives expressing human FLT3 mutants were made IL3 independent and FLT3 dependent.