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. Tyrphostin AG 879 is a dual HER2 and Trk inhibitor with IC50 values of 1μM and 10μM, respectively[1]. Treatment with 100μM Tyrphostin AG879 in PC12 cells showed inhibition of Trk-A phosphorylation[2]. Exposure to 20μM Tyrphostin AG 879 for 24h led to decreased phosphorylation of ERK-1 and 2 and decreased protein levels of RAF-1 and HER-2 in MCF-7 cells. Tyrphostin AG 879 at concentration<20μM dose-dependently reduced cell growth of MCF-7, MDA-MB-231 and SK-BR-3 cells[3]. Blocking Trk in vivo by ICV infusions of Tyrphostin AG879 (10μl, 0.5mM in DMSO 10% (V/V) in PBS) impaired both short-term and long-term recognition memory[4].
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