Human epidermal growth factor receptor (EGFR; HER1,erbB1), human epidermal growth factor r eceptor 2 (HER2; erbB2), HER3 (erbB3) and HER4 (erbB4) are members of the ErbB family of transmembrane receptor tyrosine kinases. Among them, HER2 is a validated and high-value target. Approximately 30% of breast cancers have an amplification of the HER2/neu gene or overexpression of its protein product, HER2. Also, overexpression of HER2 occurs in gastric, colorectal, NSCLC and ovarian cancers. Irbinitinib is a selective and potent HER2 inhibitor with IC50 value of 8nM, ~500-fold selective for HER2 than EGFR, thus avoiding EGFR-related side effects[1]. Irbinitinib had very good PK/ADME properties both in vitro and in vivo and showed excellent activity in numerous mouse tumor models, including breast (BT-474, MDA-MB-453), ovarian (SKOV-3) and gastric (N87) carcinoma models. Daily oral treatment with Irbinitinib for 90 days achieved tumor growth inhibition by 50% at 50mg/kg and 96% at 100mg/kg in BT-474 model. Daily oral treatment with Irbinitinib, BID, for 90 days achieved tumor growth inhibition by 39% at 50 mg/kg and by 96% at 100 mg/kg in an SKOV-3 model[2].
搜索
