title: Challenges in the Discovery of Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitors.
abstract: Since the discovery of indoleamine 2,3-dioxygenase 1 (IDO1) as an attractive target for anticancer therapy in 2003, the search for inhibitors has been intensely pursued both in academia and in pharmaceutical companies. Many novel IDO1 inhibitor scaffolds have been described, and a few potent compounds have entered clinical trials. However, a significant number of the reported compounds contain problematic functional groups, suggesting that enzyme inhibition could be the result of undesirable side reactions instead of selective binding to IDO1. Here, we describe issues in the employed experimental protocols, review and classify reported IDO1 inhibitors, and suggest different approaches for confirming viable inhibitor scaffolds.
authors.affiliation: Molecular Modeling Group, SIB Swiss Institute of Bioinformatics , CH-1015 Lausanne, Switzerland.
authors.forename: Ute F
authors.initials: UF
authors.lastname: Röhrig
authors.affiliation: Molecular Modeling Group, SIB Swiss Institute of Bioinformatics , CH-1015 Lausanne, Switzerland.|Laboratory of Glycochemistry and Asymmetric Synthesis, Ecole Polytechnique Fédérale de Lausanne (EPFL) , CH-1015 Lausanne, Switzerland.
authors.forename: Somi Reddy
authors.initials: SR
authors.lastname: Majjigapu
authors.affiliation: Laboratory of Glycochemistry and Asymmetric Synthesis, Ecole Polytechnique Fédérale de Lausanne (EPFL) , CH-1015 Lausanne, Switzerland.|Ludwig Center for Cancer Research of the University of Lausanne , CH-1015 Lausanne, Switzerland.
authors.forename: Pierre
authors.initials: P
authors.lastname: Vogel
authors.affiliation: Molecular Modeling Group, SIB Swiss Institute of Bioinformatics , CH-1015 Lausanne, Switzerland.
authors.forename: Vincent
authors.initials: V
authors.lastname: Zoete
authors.affiliation: Molecular Modeling Group, SIB Swiss Institute of Bioinformatics , CH-1015 Lausanne, Switzerland.|Ludwig Center for Cancer Research of the University of Lausanne , CH-1015 Lausanne, Switzerland.|Department of Oncology, University of Lausanne and Centre Hospitalier Universitaire Vaudois (CHUV) , CH-1011 Lausanne, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Michielin
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D055808:Drug Discovery; D057075:Enzyme Assays; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors*; D007700:Kinetics; D013329:Structure-Activity Relationship; D014364:Tryptophan / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D014364:Tryptophan