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.
TAS0728 covalently binds to the recombinant human HER2 cytoplasmic domain, modified cysteine residue C805.
TAS0728 inhibits EGFR recombinant with IC50 of 65 nM, shows excellent selectivity in a panel of 374 kinases.
TAS0728 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.
TAS0728 induced tumor regression in mouse xenograft models bearing HER2 signal-dependent tumors and exhibited a survival benefit without any evident toxicity.
