Abstract: AIM: To investigate the effects and mechanisms of BPI-2009, an orally active inhibitor of EGFR (Epidermal Growth Factor Receptor) tyrosine ki-nase on cancer therapy, and evaluate BPI-2009 as an an-ti-cancer drug targeting EGFR.METHODS: The tyro-sine kinase inhibition and the EGFR autophosphorylation inhibition of BPI-2009 were detected by Western Blot analysis.Cell growth inhibition was determined by MTT assays.In vitro tumor xenografts studies were tested in nude mice carried with A431 epidermoid tumor xenografts.RESULTS: BPI-2009, a leading com-pounds, was a potent inhibitor of EGFR kinase with an IC 50 of 5 nmol°L^-1 (completed inhibitory concentration at 62.5 nmol°L^-1), and it had no inhibitory activities a-gainst Abl, Abl-related gene (Arg) and c-Src tyrosine ki-nases at 100 nmol°L^-1. BPI-2009 blocked EGFR-medi-ated intracellular tyrosine phosphorylation (IC₅₀ 45nmol°L^-1) in the human epidermoidA431 carcinoma cell line.In cell proliferation assays, tumor cell growth was inhibited by BPI-2009 in the presence of FCS.In studies of nude mice which carried human-derived tumor, BPI-2009 produced significant and dose-dependent anti-tumor effects (human epidermoid A431 carcinoma). When oral-ly administered 100 mg°kg^-1 BPI-2009 once a day, total 24 days in mice, there was no mortality or obviously body weight loss during the treatment. CONCLUSION: BPI-2009 isan selective anti-cancer drug targeting EGFR tyro-sine kinase.

Key words: tyrosine kinase, epidermal growth factor receptor (EFGR), autophosphorylation, cell growth inhi-bition, anti-cancer effect