Design, synthesis, and evaluation of potent and selective benzoyleneurea-based inhibitors of protein geranylgeranyltransferase-I

Dora Carrico, Michelle A. Blaskovich, Cynthia J. Bucher, Saïd M. Sebti, Andrew D. Hamilton

Research output: Contribution to journalArticle


A series of novel protein geranylgeranyltransferase-I (PGGTase-I) inhibitors based on a benzoyleneurea scaffold has been synthesized. Using a benzoyleneurea scaffold as a mimetic for the central dipeptide (AA), we have developed CAAX peptidomimetic inhibitors that selectively block the activity of PGGTase-I over the closely related enzyme protein farnesyltransferase. In this new class of PGGTase-I inhibitors, compound (6c) with X = L-phenylalanine, displayed the highest inhibition activity against PGGTase-I with an IC 50 value of 170 nM. The inhibitors described in this study represent novel and promising leads for the development of potent and selective inhibitors of mammalian PGGTase-I for potential application as antitumor agents.

Original languageEnglish (US)
Pages (from-to)677-688
Number of pages12
JournalBioorganic and Medicinal Chemistry
Issue number3
StatePublished - Feb 1 2005



  • Antitumor agents
  • Farnesyltransferase
  • Geranylgeranyltransferase-I
  • Peptidomimetics

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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