title: Discovery and preliminary SARs of keto-indoles as novel indoleamine 2,3-dioxygenase (IDO) inhibitors.
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.
authors.affiliation: Drug Design and Discovery Center, University of Namur, 61 Rue de Bruxelles, 5000 Namur, Belgium.
authors.forename: Eduard
authors.initials: E
authors.lastname: Dolušić
authors.forename: Pierre
authors.initials: P
authors.lastname: Larrieu
authors.forename: Sébastien
authors.initials: S
authors.lastname: Blanc
authors.forename: Frédéric
authors.initials: F
authors.lastname: Sapunaric
authors.forename: Jenny
authors.initials: J
authors.lastname: Pouyez
authors.forename: Laurence
authors.initials: L
authors.lastname: Moineaux
authors.forename: Delphine
authors.initials: D
authors.lastname: Colette
authors.forename: Vincent
authors.initials: V
authors.lastname: Stroobant
authors.forename: Luc
authors.initials: L
authors.lastname: Pilotte
authors.forename: Didier
authors.initials: D
authors.lastname: Colau
authors.forename: Thierry
authors.initials: T
authors.lastname: Ferain
authors.forename: Graeme
authors.initials: G
authors.lastname: Fraser
authors.forename: Moreno
authors.initials: M
authors.lastname: Galleni
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Frère
authors.forename: Bernard
authors.initials: B
authors.lastname: Masereel
authors.forename: Benoît
authors.initials: B
authors.lastname: Van den Eynde
authors.forename: Johan
authors.initials: J
authors.lastname: Wouters
authors.forename: Raphaël
authors.initials: R
authors.lastname: Frédérick
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry*; D045744:Cell Line, Tumor; D062126:Databases, Chemical; D055808:Drug Discovery; D057075:Enzyme Assays; D004791:Enzyme Inhibitors / Q000737:chemistry*; D004926:Escherichia coli / Q000235:genetics; D015870:Gene Expression; D057166:High-Throughput Screening Assays; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D007211:Indoles / Q000737:chemistry*; D051379:Mice; D062105:Molecular Docking Simulation; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D013329:Structure-Activity Relationship; D014364:Tryptophan / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007211:Indoles; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D014364:Tryptophan