Inhibition of Ras prenylation

A signaling target for novel anti-cancer drug design

Edwina C. Lerner, Andrew Hamilton, Saïd M. Sebti

Research output: Contribution to journalArticle

Abstract

The cancer-causing activity of Ras requires the prenylation of a cysteine fourth from its carboxyl terminus. Rational design of peptidomimetics of the carboxyl terminal tetrapeptide prenylation site on Ras resulted in pharmacological agents capable of inhibiting Ras processing, selectively antagonizing oncogenic signaling and suppressing human tumor growth in mouse models without side effects. This mini-review describes the efforts of several groups to design, synthesize and evaluate the biological activities of farnesyltransferase and geranylgeranyltransferase I inhibitors. Among the important issues that will be discussed are the mechanism of action of these inhibitors and the potential mechanisms of resistance to inhibition of K-Ras farnesylation.

Original languageEnglish (US)
Pages (from-to)229-238
Number of pages10
JournalAnti-Cancer Drug Design
Volume12
Issue number4
StatePublished - Jun 1997

Fingerprint

Prenylation
Drug Design
Farnesyltranstransferase
Peptidomimetics
Bioactivity
Pharmaceutical Preparations
Cysteine
Tumors
Neoplasms
Action Potentials
Processing
Pharmacology
Growth
geranylgeranyltransferase type-I

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Organic Chemistry
  • Oncology
  • Drug Discovery
  • Pharmacology

Cite this

Inhibition of Ras prenylation : A signaling target for novel anti-cancer drug design. / Lerner, Edwina C.; Hamilton, Andrew; Sebti, Saïd M.

In: Anti-Cancer Drug Design, Vol. 12, No. 4, 06.1997, p. 229-238.

Research output: Contribution to journalArticle

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