Abstract
The selective inhibition of COX-2 isozymes should lead to a new generation of NSAIDs with significantly reduced side effects; e.g. celecoxib (Celebrex) and rofecoxib (Vioxx). To obtain inhibitors with higher selectivity it has become essential to gain additional insight into the details of the interactions between COX isozymes-and NSAIDs. Although X-ray structures of COX-2 complexed with a small number of ligands are available, experimental data are missing for two well-known selective COX-2 inhibitors (rofecoxib and nimesulide) and docking results reported are controversial. We use a combination of a traditional docking procedure with a new computational tool (Contact Statistics analysis) that identifies the best orientation among a number of solutions to shed some light on this topic.
MeSH terms
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Algorithms*
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Anti-Inflammatory Agents, Non-Steroidal / chemistry*
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Anti-Inflammatory Agents, Non-Steroidal / metabolism
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Binding Sites
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Crystallography, X-Ray
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Cyclooxygenase 2
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors / chemistry
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Cyclooxygenase Inhibitors / metabolism
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Flurbiprofen / chemistry
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Flurbiprofen / metabolism
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Humans
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Isoenzymes / chemistry
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Isoenzymes / metabolism
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Lactones / chemistry
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Lactones / metabolism
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Membrane Proteins
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Models, Molecular*
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Models, Statistical*
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Molecular Conformation
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Molecular Structure
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Prostaglandin-Endoperoxide Synthases / chemistry*
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Prostaglandin-Endoperoxide Synthases / metabolism
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Protein Binding
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Pyrazoles / chemistry
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Pyrazoles / metabolism
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Sulfonamides / chemistry
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Sulfonamides / metabolism
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Sulfones / chemistry
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Sulfones / metabolism
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors
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Isoenzymes
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Lactones
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Membrane Proteins
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Pyrazoles
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SC 558
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Sulfonamides
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Sulfones
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rofecoxib
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Flurbiprofen
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Cyclooxygenase 2
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PTGS2 protein, human
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Prostaglandin-Endoperoxide Synthases
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nimesulide