TABLE 1

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 *.

Compounds
AfatinibBI 37781LapatinibCanertinibErlotinibGefinitib
ErbB-4 kinase
    Value1544301579323
    Range0.7–1.7510–54418–300.8–10579–756293–323
    n423422
EGFRWT kinase
    Value0.50.8
    Range0.2–0.70.8–10.3–170.3*–1.70.9–1.70.4–4.7
    n526546
EGFRL858R kinase
    Value0.21
    Range0.2–0.4*1–22–8*0.4–0.8*1.1–2.70.8–1.4
    n223232
EGFRL858R/T790M kinase
    Value957
    Range9–10*36–57>400018–361520–3562534–1267
    n223334
HER2 kinase
    Value1484
    Range7–2584–1126–2522–72238–698416–1830
    n524336
Phospho EGFR (A431), EGFR WT kinase
    Value817
    Range8–13*17–5693–14517–22*3–822–63
    n424554
Phospho EGFR (NCI-H1975), EGFR L858R/T790M
    Value491610
    Range49–1291458–1610>4000*76–88>4000*>4000*
    n522333
Phospho HER2 (BT474), HER2 gene amplification
    Value75570
    Range35*–75570–123774–10288–184*396–9303600–3710*
    n533232
Proliferation (NCI-H1975), L858R/T790M (three-dimensional assays)
    Value92>3000
    Range92–225>3000>4000*57–307>4000*>4000*
    n422433
Proliferation (BT474), HER2 gene amplification, two-dimensional assays.
    Value54>4000
    Range12–56>400012–12837–66599–8991070–1960
    n533333