title: Novel bisphosphonate inhibitors of the human farnesyl pyrophosphate synthase.
abstract: A structure-based approach was pursued in designing novel bisphosphonate inhibitors of the human farnesyl pyrophosphate synthase (hFPPS). Preliminary SAR and structural evidence for the simultaneous binding of these inhibitors into the isopentenyl pyrophosphate (IPP) and the geranyl pyrophosphate (GPP) substrate sub-pockets of the enzyme are presented.
authors.affiliation: Department of Chemistry, McGill University, Montreal, Quebec, Canada.
authors.forename: Joris W
authors.initials: JW
authors.lastname: De Schutter
authors.forename: Serge
authors.initials: S
authors.lastname: Zaretsky
authors.forename: Sarah
authors.initials: S
authors.lastname: Welbourn
authors.forename: Arnim
authors.initials: A
authors.lastname: Pause
authors.forename: Youla S
authors.initials: YS
authors.lastname: Tsantrizos
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D004164:Diphosphonates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D012968:Etidronic Acid / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D051232:Geranylgeranyl-Diphosphate Geranylgeranyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D045782:Hemiterpenes / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000494:pharmacology; D011106:Polyisoprenyl Phosphates / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D000068296:Risedronic Acid; D013329:Structure-Activity Relationship
chemical_list: D004164:Diphosphonates; D004791:Enzyme Inhibitors; D045782:Hemiterpenes; D009943:Organophosphorus Compounds; D011106:Polyisoprenyl Phosphates; C004809:isopentenyl pyrophosphate; C015234:geranyl pyrophosphate; D051232:Geranylgeranyl-Diphosphate Geranylgeranyltransferase; D000068296:Risedronic Acid; D012968:Etidronic Acid