TAS0728

TAS0728 is an oral, small molecule covalent-binding inhibitor that selectively targets human epidermal growth factor receptor 2 (HER2/ERBB2) kinase. It irreversibly binds to HER2 at cysteine residue C805 and inhibits its kinase activity with high specificity over wild-type EGFR. Preclinical studies demonstrated robust inhibition of phosphorylation of both mutated and wild-type HER2 as well as downstream effectors such as HER3, leading to apoptosis in HER2-amplified cancer cells and tumor regression in xenograft models. Clinical development focused on advanced solid tumors with HER2 or HER3 overexpression, amplification or mutation—including breast cancer, non-small cell lung cancer (NSCLC), colorectal cancer, biliary tract cancers, endometrial carcinoma, esophageal cancer and transitional cell carcinoma—particularly in patients who had progressed despite standard therapies. However, clinical trials were terminated due to unacceptable toxicity including severe diarrhea and a fatal cardiac arrest possibly related to the drug[1][4][6][10].

Other names

TAS0728TAS-0728TAS 0728TPC 107TPC107TPC-107