Mutated ras oncogenes are frequently found in many human cancers,most notably cancers of the pancreas(90%),colon(50%)and lung(30%).The oncogenic products Ras p21 are synthesized as cytosolic proteins,which undergo post-translational modifications before they assume proliferative function.The first and obligatory step is farnesylation of Ras proteins,which is catalyzed by farnesyltransferase(FT).This talk relates to the designs,syntheses,and SAR studies of tetrahydrobenzodiazepine class of farnesyltransferase inhibitors originated from a peptide mimetic inhibitor.These benzodiazepine inhibitors demonstrated inhibiting tumor growth in mice bearing human tumor xenografts.Optimization of in vivo antitumor activity results in identification of a preclinical candidate,which went into human clinical trials for cancer treatment.