Inhibition of Ras prenylation: a novel approach to cancer chemotherapy

Pharmacol Ther. 1997;74(1):103-14. doi: 10.1016/s0163-7258(97)00014-4.


The demonstration that Ras requires prenylation for its cancer-causing activity led several groups of investigators to an intense search for farnesyltransferase and geranylgeranyltransferase inhibitors as potential anticancer drugs. Rational design of small organic molecules that mimic the carboxyl terminal tetrapeptide prenylation site on Ras resulted in pharmacological agents capable of inhibiting Ras processing and selectively antagonizing oncogenic signaling, and suppressing human tumor growth in mouse models without side effects. These agents presently are undergoing advanced preclinical studies. This review describes the efforts of several groups to design, synthesize and evaluate the biological activities of several classes of prenyltransferase inhibitors. Several important issues, such as mechanism of action of prenyltransferase inhibitors and potential mechanisms of resistance to inhibition of K-Ras farnesylation, are also discussed.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Alkyl and Aryl Transferases / antagonists & inhibitors*
  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / standards
  • Drug Design
  • Farnesyltranstransferase
  • Humans
  • Neoplasms / drug therapy
  • Protein Prenylation / drug effects
  • ras Proteins / genetics*


  • Antineoplastic Agents
  • Alkyl and Aryl Transferases
  • geranylgeranyltransferase type-I
  • Farnesyltranstransferase
  • ras Proteins