Abstract
A series of 2-arylindole-3-acetamide farnesyl protein transferase inhibitors has been identified. The compounds inhibit the enzyme in a farnesyl pyrophosphate-competitive manner and are selective for farnesyl protein transferase over the related enzyme geranylgeranyltransferase-I. A representative member of this series of inhibitors demonstrates equal effectiveness against HDJ-2 and K-Ras farnesylation in a cell-based assay when geranylgeranylation is suppressed.
MeSH terms
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Alkyl and Aryl Transferases / antagonists & inhibitors*
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Alkyl and Aryl Transferases / metabolism
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Carrier Proteins / metabolism
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / metabolism
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Enzyme Inhibitors / pharmacology
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HSP40 Heat-Shock Proteins
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Heat-Shock Proteins / metabolism
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Humans
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Indoleacetic Acids / chemical synthesis
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Indoleacetic Acids / metabolism*
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Indoleacetic Acids / pharmacology*
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Protein Prenylation / drug effects*
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Protein Prenylation / physiology
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Structure-Activity Relationship
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Tumor Cells, Cultured
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ras Proteins / metabolism*
Substances
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Carrier Proteins
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DNAJA1 protein, human
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Enzyme Inhibitors
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HSP40 Heat-Shock Proteins
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Heat-Shock Proteins
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Indoleacetic Acids
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indoleacetamide
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Alkyl and Aryl Transferases
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geranylgeranyltransferase type-I
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p21(ras) farnesyl-protein transferase
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ras Proteins