title: 2-Arylindole-3-acetamides: FPP-competitive inhibitors of farnesyl protein transferase.
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.
authors: Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. bwesley_trotter@merck.com
authors: B W
authors: BW
authors: Trotter
authors: A G
authors: AG
authors: Quigley
authors: W C
authors: WC
authors: Lumma
authors: J T
authors: JT
authors: Sisko
authors: E S
authors: ES
authors: Walsh
authors: C S
authors: CS
authors: Hamann
authors: R G
authors: RG
authors: Robinson
authors: H
authors: H
authors: Bhimnathwala
authors: D G
authors: DG
authors: Kolodin
authors: W
authors: W
authors: Zheng
authors: C A
authors: CA
authors: Buser
authors: H E
authors: HE
authors: Huber
authors: R B
authors: RB
authors: Lobell
authors: N E
authors: NE
authors: Kohl
authors: T M
authors: TM
authors: Williams
authors: S L
authors: SL
authors: Graham
authors: C J
authors: CJ
authors: Dinsmore
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D050956:HSP40 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007210:Indoleacetic Acids / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology*; D017368:Protein Prenylation / Q000187:drug effects* / Q000502:physiology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C107481:DNAJA1 protein, human; D004791:Enzyme Inhibitors; D050956:HSP40 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D007210:Indoleacetic Acids; C015950:indoleacetamide; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I; C064911:p21(ras) farnesyl-protein transferase; D018631:ras Proteins