title: Orally bioavailable farnesyltransferase inhibitors as anticancer agents in transgenic and xenograft models.
abstract: The in vivo evaluation process described here was instrumental in the identification of SCH 66336 as a clinical candidate. Our lead FTI, SCH 66336, and several other FTIs are being evaluated in early-phase clinical trials to establish proof-of-principle for farnesyl transferase inhibition in human patients. The preclinical studies described here suggest that FTIs may have utility against a wide array of human cancers as a single agent and may, at least in some cases, lead to tumor regression. In addition, the results to date in combination with cytotoxic chemotherapeutic agents in animal models indicate that these combinations may enhance the clinical efficacy of FPT inhibitors. Further preclinical studies should help to guide the clinical development of this class of novel antitumor agents.
authors.affiliation: Schering-Plough Research Institute, Kenilworth, New Jersey 07033-1300, USA.
authors.forename: M
authors.initials: M
authors.lastname: Liu
authors.forename: W R
authors.initials: WR
authors.lastname: Bishop
authors.forename: L L
authors.initials: LL
authors.lastname: Nielsen
authors.forename: M S
authors.initials: MS
authors.lastname: Bryant
authors.forename: P
authors.initials: P
authors.lastname: Kirschmeier
mesh_terms: D016475:3T3 Cells; D000284:Administration, Oral; D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity; D017209:Apoptosis; D001682:Biological Availability; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D004791:Enzyme Inhibitors / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity; D051231:Farnesyltranstransferase; D005347:Fibroblasts / Q000378:metabolism; D011905:Genes, ras; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009369:Neoplasms / Q000378:metabolism; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase