CA1A2X-competitive inhibitors of farnesyltransferase as anti-cancer agents.
For Ras oncoproteins to transform mammalian cells, they must be post-translationally farnesylated in a reaction catalysed by the enzyme farnesyl-protein transferase (FPTase). Inhibitors of FPTase have therefore been proposed as anti-cancer agents. In this review Charles Omer and Nancy Kohl discuss the development of FPTase inhibitors that are kinetically competitive with the protein substrate in the farnesylation reaction. These compounds are potent and selective inhibitors of the enzyme that block the tumourigenic phenotypes of ras-transformed cells and human tumour cells in cell culture and in animal models.
Omer
C A
CA
Department of Cancer Research, Merck Research Laboratories, West Point, PA 19486, USA.
Kohl
N E
NE
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D051231:Farnesyltranstransferase; D006801:Humans; D011487:Protein Conformation
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase