Abstract
A series of imidazole-containing biphenyls was prepared and evaluated in vitro for inhibition of FTase and cellular Ras processing. Several of these analogues, such as 21, are potent inhibitors of FTase (<1nM), FTase/GGTase selective (>300-fold) and cellularly active (<or=80nM). An X-ray crystal structure of inhibitor 21 bound to rat farnesyltransferase is also presented.
MeSH terms
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3T3 Cells
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Alkyl and Aryl Transferases / antagonists & inhibitors*
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Animals
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Biological Availability
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Biphenyl Compounds / chemical synthesis*
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Biphenyl Compounds / pharmacokinetics
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Biphenyl Compounds / pharmacology*
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Crystallography, X-Ray
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacokinetics
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Enzyme Inhibitors / pharmacology*
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Farnesyltranstransferase
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Genes, ras / drug effects
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Half-Life
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Imidazoles / chemical synthesis*
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Imidazoles / pharmacokinetics
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Imidazoles / pharmacology*
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Indicators and Reagents
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Mice
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Models, Molecular
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Rats
Substances
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Biphenyl Compounds
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Enzyme Inhibitors
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Imidazoles
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Indicators and Reagents
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Alkyl and Aryl Transferases
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geranylgeranyltransferase type-I
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Farnesyltranstransferase