Inhibition of human tumor xenograft growth by treatment with the farnesyl transferase inhibitor B956.

摘要: Abstract ras oncogenes are present in several types of cancers but most frequently described colon and pancreatic carcinomas. Consequently, is being targeted for drug development as a means to develop therapies these cancer. The protein posttranslationally modified by the addition farnesyl group, followed cleavage COOH-terminal 3 amino acids methylation prenylated cysteine. Because posttranslational obligatory not only remaining modifications take place also control cell growth, inhibitors farnesylation developed potential antitumor agents. In this report, new peptidomimetic inhibitor transferase described. This compound, B956, its methyl ester B1086, inhibit formation colonies soft agar 14 human tumor lines expressing different at concentrations between 0.2 60 µm. Higher B956 (10–80 µm) were required colony 5 without mutations. B956/B1086 100 mg/kg inhibited growth EJ-1 bladder carcinoma, HT1080 fibrosarcoma, lesser extent HCT116 carcinoma xenografts nude mice. Furthermore, inhibition shown be correlated with processing tumor. Thus, have therapy ras-dependent tumors.