TAS0728 is a potent, selective, orally active, irreversible and covalent-binding HER2 inhibitor, with an IC 50 of 13 nM. TAS0728 also shows IC 50 s of 4.9, 8.5, 31, 65, 33, 25 and 86 nM for BMX 、 HER4 、 BLK 、EGFR、 JAK3 、 SLK and LOK respectively. Furthermore, TAS0728 exhibits robust and sustained inhibition of the phosphorylation of HER2 , HER3 , and downstream effectors.