Abstract
Indoleamine 2,3-dioxygenase (IDO) is an important new therapeutic target for the treatment of cancer. With the aim of discovering novel IDO inhibitors, a virtual screen was undertaken and led to the discovery of the keto-indole derivative 1a endowed with an inhibitory potency in the micromolar range. Detailed kinetics were performed and revealed an uncompetitive inhibition profile. Preliminary SARs were drawn in this series and corroborated the putative binding orientation as suggested by docking.
Copyright © 2011 Elsevier Masson SAS. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents / chemistry*
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Cell Line, Tumor
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Databases, Chemical
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Drug Discovery
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Enzyme Assays
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Enzyme Inhibitors / chemistry*
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Escherichia coli / genetics
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Gene Expression
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High-Throughput Screening Assays
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Humans
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Indoleamine-Pyrrole 2,3,-Dioxygenase / antagonists & inhibitors*
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Indoleamine-Pyrrole 2,3,-Dioxygenase / chemistry
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Indoleamine-Pyrrole 2,3,-Dioxygenase / genetics
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Indoles / chemistry*
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Mice
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Molecular Docking Simulation*
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Neoplasm Proteins / antagonists & inhibitors*
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Neoplasm Proteins / chemistry
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Neoplasm Proteins / genetics
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Structure-Activity Relationship
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Tryptophan / chemistry
Substances
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Antineoplastic Agents
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Enzyme Inhibitors
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Indoleamine-Pyrrole 2,3,-Dioxygenase
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Indoles
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Neoplasm Proteins
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Recombinant Proteins
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Tryptophan