Farnesyltransferase inhibitors as anticancer agents: critical crossroads

Curr Opin Drug Discov Devel. 2004 Jul;7(4):478-86.


Farnesyltransferase (FT) inhibitors were originally designed as anticancer agents, and were thought to act by inhibiting the farnesylation of mutant Ras proteins. However, these compounds were subsequently demonstrated to have antitumor effects even in the absence of Ras mutations and it has now become clear that other protein targets are involved. This article discusses the preclinical and clinical development of FT inhibitors. To date, tipifarnib (Zarnestra; Janssen Pharmaceutica NV) and lonafarnib (Sarasar; Schering-Plough Research Institute) are the only two FT inhibitors to have been evaluated in phase III clinical trials. The clinical results of these two compounds are presented below, with emphasis on ways of enhancing the possibility of a successful FT inhibitor anticancer drug. Details of new FT inhibitors disclosed since the beginning of 2003 are also included.

Publication types

  • Review

MeSH terms

  • Alkyl and Aryl Transferases / antagonists & inhibitors*
  • Alkyl and Aryl Transferases / pharmacology
  • Alkyl and Aryl Transferases / therapeutic use*
  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Drug Delivery Systems
  • Drug Screening Assays, Antitumor
  • Farnesyltranstransferase
  • Humans
  • Molecular Structure
  • Oncogene Proteins / biosynthesis
  • Oncogene Proteins / drug effects


  • Antineoplastic Agents
  • Oncogene Proteins
  • Alkyl and Aryl Transferases
  • Farnesyltranstransferase