Tucatinib is an inhibitor of HER2 (IC50 = 14 nM).1 It inhibits the phosphorylation of HER2 in BT474 breast carcinoma cells (IC50 = 21 nM). Tucatinib inhibits phosphorylation of AKT and induces apoptosis in BT474 cells. In vivo, tucatinib (25-100 mg/kg) inhibits tumor growth in NCI N87 gastric carcinoma and SKOV3 ovarian adenocarcinoma mouse xenograft models. Tucatinib also reduces intratumor phosphorylation of AKT and ERK and inhibits tumor growth in a BT474 mouse xenograft model.
1.Pheneger, T., Bouhana, K., Anderson, D., et al.Abstract #1795: In vitro and in vivo activity of ARRY-380: A potent, small molecule inhibitor of ErbB2AACR Cancer Res.69(9)1795(2009)