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.
Copyright (c) 2010 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Binding Sites
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Computer Simulation
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Diphosphonates / chemical synthesis
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Diphosphonates / chemistry*
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Diphosphonates / pharmacology
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / pharmacology
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Etidronic Acid / analogs & derivatives
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Etidronic Acid / chemistry
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Etidronic Acid / pharmacology
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Geranylgeranyl-Diphosphate Geranylgeranyltransferase / antagonists & inhibitors*
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Geranylgeranyl-Diphosphate Geranylgeranyltransferase / metabolism
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Hemiterpenes / chemistry
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Hemiterpenes / pharmacology
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Humans
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Organophosphorus Compounds / chemistry
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Organophosphorus Compounds / pharmacology
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Polyisoprenyl Phosphates / chemistry
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Polyisoprenyl Phosphates / pharmacology
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Protein Binding
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Risedronic Acid
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Structure-Activity Relationship
Substances
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Diphosphonates
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Enzyme Inhibitors
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Hemiterpenes
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Organophosphorus Compounds
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Polyisoprenyl Phosphates
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isopentenyl pyrophosphate
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geranyl pyrophosphate
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Geranylgeranyl-Diphosphate Geranylgeranyltransferase
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Risedronic Acid
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Etidronic Acid