TAS 0728 is a covalent HER2 inhibitor (IC50 = 36 nM).1 It is selective for HER2 over panels of 386 and 374 additional kinases, as well as a panel of 68 non-kinase enzymes, when used at a concentration of 1 ?M. TAS 0728 inhibits HER2 autophosphorylation in HER2-overexpressing SK-BR-3 cells but not autophosphorylation of EGFR in EGFR-overexpressing A431 cells. It inhibits the growth of six HER2-amplified breast, lung, and gastric cancer cell lines (GI50s = 1.6-31 nM). TAS 0278 (30 and 60 mg/kg) reduces tumor volume in NCI N87 and BT474 mouse xenograft models.
1.Irie, H., Ito, K., Fujioka, Y., et al.TAS0728, a covalent-binding, HER2-selective kinase inhibitor shows potent antitumor activity in preclinical modelsMol. Cancer Ther.18(4)733-742(2019)