Challenges in the Discovery of Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitors.

Röhrig UF; Majjigapu SR; Vogel P; Zoete V; Michielin O

doi:10.1021/acs.jmedchem.5b00326

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Journal article

Challenges in the Discovery of Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitors.

Röhrig UF Molecular Modeling Group, SIB Swiss Institute of Bioinformatics , CH-1015 Lausanne, Switzerland.
Majjigapu SR Molecular Modeling Group, SIB Swiss Institute of Bioinformatics , CH-1015 Lausanne, Switzerland.
Vogel P Laboratory of Glycochemistry and Asymmetric Synthesis, Ecole Polytechnique Fédérale de Lausanne (EPFL) , CH-1015 Lausanne, Switzerland.
Zoete V Molecular Modeling Group, SIB Swiss Institute of Bioinformatics , CH-1015 Lausanne, Switzerland.
Michielin O Molecular Modeling Group, SIB Swiss Institute of Bioinformatics , CH-1015 Lausanne, Switzerland.

2015-05-14

Published in:

Journal of medicinal chemistry. - 2015

Indoleamine-Pyrrole 2,3,-Dioxygenase

Structure-Activity Relationship

English 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.

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