Abstract
Tetrahydroquinoline-based small molecule inhibitors of farnesyltransferase (FT) have been identified. Lead compounds were shown to have nanomolar to sub-nanomolar activity in biochemical assays with excellent potency in a Ras-mutated cellular reversion assay. BMS-316810 (9e), a 0.7 nM FT inhibitor, was orally-active in a nude mouse tumor allograft efficacy study.
MeSH terms
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Alkyl and Aryl Transferases / antagonists & inhibitors*
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Animals
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / pharmacology
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Cell Line, Tumor
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Drug Screening Assays, Antitumor
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology
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Farnesyltranstransferase
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Mice
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Mice, Nude
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Quinolines / chemical synthesis*
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Quinolines / pharmacology
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Structure-Activity Relationship
Substances
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Antineoplastic Agents
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Enzyme Inhibitors
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Quinolines
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Alkyl and Aryl Transferases
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Farnesyltranstransferase