The synthesis and biological evaluation of a series of potent dual inhibitors of farnesyl and geranyl-Geranyl protein transferases

Bioorg Med Chem Lett. 2002 Aug 5;12(15):2027-30. doi: 10.1016/s0960-894x(02)00308-6.

Abstract

We have prepared a series of potent, dual inhibitors of the prenyl transferases farnesyl protein transferase (FPTase) and geranyl-geranyl protein transferase I (GGPTase). The compounds were shown to possess potent activity against both enzymes in cell culture. Mechanistic analysis has shown that the compounds are CAAX competitive for FPTase inhibition but geranyl-geranyl pyrophosphate (GGPP) competitive for GGPTase inhibiton.

MeSH terms

  • Alkyl and Aryl Transferases / antagonists & inhibitors*
  • Binding Sites
  • Binding, Competitive
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Inhibitory Concentration 50
  • Protein Binding
  • Structure-Activity Relationship
  • Tumor Cells, Cultured
  • rap GTP-Binding Proteins / drug effects
  • rap GTP-Binding Proteins / metabolism

Substances

  • Enzyme Inhibitors
  • Alkyl and Aryl Transferases
  • geranylgeranyltransferase type-I
  • p21(ras) farnesyl-protein transferase
  • rap GTP-Binding Proteins