title: Identification of benzofuran-4,5-diones as novel and selective non-hydroxamic acid, non-peptidomimetic based inhibitors of human peptide deformylase.
abstract: Selective inhibitors of human peptide deformylase (HsPDF) are predicted to constitute a new class of antitumor agents. We report the identification of benzofuran-4,5-diones as the first known selective HsPDF inhibitors and we describe their selectivity profile in a panel of metalloproteases. We characterize their structure-activity relationships for antitumor activity in a panel of cancer cell lines, and we assess their in vivo efficacy in a mouse xenograft model. Our results demonstrate that selective HsPDF inhibitors based on the benzofuran-4,5-dione scaffold constitute a novel class of antitumor agents that are potent in vitro and in vivo.
authors: Department of Molecular Pharmacology and Chemistry, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors: Christophe
authors: C
authors: Antczak
authors: David
authors: D
authors: Shum
authors: Bhramdeo
authors: B
authors: Bassit
authors: Mark G
authors: MG
authors: Frattini
authors: Yueming
authors: Y
authors: Li
authors: Elisa
authors: E
authors: de Stanchina
authors: David A
authors: DA
authors: Scheinberg
authors: Hakim
authors: H
authors: Djaballah
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity; D001572:Benzofurans / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry; D045726:Metalloproteases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy; D013329:Structure-Activity Relationship; D014183:Transplantation, Heterologous
chemical_list: D000970:Antineoplastic Agents; D001572:Benzofurans; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D045726:Metalloproteases; D000581:Amidohydrolases; C084507:peptide deformylase; C105430:benzofuran