[Inhibitors of Ras farnesylation: tomorrow's anticancer agents?].
Increasing evidence implicates a critical role for aberrant Ras function in promoting the development of human tumours and has provided the impetus for identifying anti-Ras drugs for therapy. In order to be active the protooncogene ras must be associated with the plasma membrane. This feature depends crucially upon its farnesylation (addition of a 15 carbon moiety) by the enzyme farnesyl protein transferase. In the search for new anticancer strategies and agents, potent and selective inhibitors of this enzyme have been designed. The more recent of these compounds have produced impressive results in vivo against human tumours xenografted onto nude mice, without notable toxicity, making them promising candidates for clinical evaluation.
Perrin
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D
Division de cancérologie expérimentale, Centre de recherche Pierre-Fabre, Castres, France.
Halazy
S
S
Hill
B
B
D019883:Alkyl and Aryl Transferases; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011905:Genes, ras / Q000235:genetics / Q000502:physiology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D017368:Protein Prenylation / Q000187:drug effects; D016283:Proto-Oncogene Proteins p21(ras) / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D014166:Transferases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D014166:Transferases; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)