tas0728

Description: TAS0728 is a potent, selective, covalent, orally bioavailable HER2 inhibitor with IC50 of 36 nM. TAS0728 bound to HER2 kinase, the inhibitory activity was not affected by a high ATP concentration. TAS0728 exhibited robust and sustained inhibition of the phosphorylation of HER2, HER3, and downstream effectors, thereby inducing apoptosis of HER2-amplified breast cancer cells and in tumor tissues of a xenograft model. TAS0728 induced tumor regression in mouse xenograft models bearing HER2 signal-dependent tumors and exhibited a survival benefit without any evident toxicity in a peritoneal dissemination mouse model bearing HER2-driven cancer cells. References: Irie H, Ito K, Fujioka Y, Oguchi K, Fujioka A, Hashimoto A, Ohsawa H, TanakaK, Funabashi K, Araki H, Kawai Y, Shimamura T, Wadhwa R, Ohkubo S, Matsuo K.TAS0728, A Covalent-binding, HER2-selective Kinase Inhibitor Shows PotentAntitumor Activity in Preclinical Models. Mol Cancer Ther. 2019Apr; 18(4):733-742. doi: 10.1158/1535-7163.MCT-18-1085. Epub 2019 Feb 20. PubMedPMID: 30787176.