The HER-2/neu proto-oncogene is a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases (RTK) which includes EGFR, HER-2/neu, HER-3 and HER-4. Overexpression of HER-2/neu occurs in 25-30% of human breast and ovarian cancer. AG-825 is a selective ATP-competitive inhibitor of the tyrosine kinase activity of HER-2/neu. In cell-free assays, AG-825 inhibits Her-2/neu, EGFR, and PDGFR autophosphorylation with IC50 values of 0.35, 19, and 40 µM, respectively. However, in select whole cells, the high concentration of ATP prevents inhibition of kinase activity by AG-825. Concentrations of 50 µM AG-825, however, consistently inhibit Her-2/neu signalling and promote killing of human LNCaP, C4, and C4-2 prostate cancer cells.