Effect of bosutinib on the allosteric activator function of HER3 in vitro. Concentration dependent effect of bosutinib on measured kinase activity in the following bosutinib binding modalities: (A) HER3 and EGFR binding (HER3 and EGFR-V924R, orange squares), (B) HER3 binding only (HER3 and EGFR-V924R/T766M, purple circles), (C) no binding (HER3-T768I and EGFR-V924R/T766M, green triangles). The small black star on the EGFR kinase domain represents the V924R mutation preventing self-activation. (D) Normalized kinase activity in response to bosutinib titration. Error bars in all plots represent SD of two independent measurements. ** P < 0.001.