Inhibition of Ras prenylation: A novel approach to cancer chemotherapy

Saïd M. Sebti, Andrew D. Hamilton

Research output: Contribution to journalReview articlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)103-114
Number of pages12
JournalPharmacology and Therapeutics
Issue number1
StatePublished - 1997


  • CAAX peptidomimetics
  • Cancer chemotherapy
  • Drug design
  • Farnesyltransferase
  • Geranylgeranyltransferase
  • Ras

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


Dive into the research topics of 'Inhibition of Ras prenylation: A novel approach to cancer chemotherapy'. Together they form a unique fingerprint.

Cite this