Potency of ErbB receptor inhibitors in molecular and cellular assays

The inhibitory constants [nM] were determined as described under Materials and Methods. All values were derived from technical duplicates and confirmed in multiple (n) independent biological experiments. Values in bold were determined in the same experiment to allow direct comparison. The range of confirmatory values that comprise 197 independent EC50 determinations includes 16 EC50 values reported previously (Li et al., 2008) marked by *.

AfatinibBI 37781LapatinibCanertinibErlotinibGefinitib
ErbB-4 kinase
EGFRWT kinase
EGFRL858R kinase
EGFRL858R/T790M kinase
HER2 kinase
Phospho EGFR (A431), EGFR WT kinase
Phospho EGFR (NCI-H1975), EGFR L858R/T790M
Phospho HER2 (BT474), HER2 gene amplification
Proliferation (NCI-H1975), L858R/T790M (three-dimensional assays)
Proliferation (BT474), HER2 gene amplification, two-dimensional assays.