TAS0728 (TAS-0728, TAS 0728) is a potent, selective, covalent, orally available inhibitor of HER2 kinase with IC50 of 36 nM in in vitro kinase assays; covalently binds to the recombinant human HER2 cytoplasmic domain, modified cysteine residue C805; inhibits EGFR recombinant with IC50 of 65 nM, shows excellent selectivity in a panel of 374 kinases; strongly inhibits the phosphorylation of HER2 in SK-BR-3 cells at 30-1000 nM, with weakly inhibition on phosphorylation of EGFR; potently inhibited the in vitro proliferation of five HER2-amplified cell lines with GI50 of <10 nM, exhibited robust and sustained inhibition of the phosphorylation of HER2, HER3; induced tumor regression in mouse xenograft models bearing HER2 signal-dependent tumors and exhibited a survival benefit without any evident toxicity.Solid TumorsPhase 2 Clinical
