[Anti tumor activity of farnesyl transferase inhibitor].
Posttranslational farnesylation by farnesyltransferase (FTase) is critical for the function of ras oncogene product and FTase has attracted attention as the new target of anticancer agents. B956 and B1352, obtained from the screening of CAAX analog inhibitors of FTase, induced flat reversion and inhibited the anchorage independent growth of ras transformant and ras mutated human tumor cell lines through the inhibition of posttranslational modification of ras p21. Inhibition of tumor growth in vivo was caused by inhibition of ras processing. Methyl ester prodrug of B956 and B1352 showed antitumor activity in ras mutated human tumor xenograft model. FTase inhibitor has the potential to be developed as therapy for ras mutated human tumors.
Yoshimatsu
K
K
Cancer & Infectious Disease Research Unit, Tsukuba Research Laboratories, Eisai Co., Ltd.
Nagasu
T
T
D019883:Alkyl and Aryl Transferases; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D051231:Farnesyltranstransferase; D006801:Humans; D008715:Methionine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009842:Oligopeptides / Q000494:pharmacology*; D015689:Oncogene Protein p21(ras) / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D014166:Transferases / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; C096694:B 956; C104392:B1352; D004791:Enzyme Inhibitors; D009842:Oligopeptides; C088459:B 581; D008715:Methionine; D014166:Transferases; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase; D015689:Oncogene Protein p21(ras)