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1,2,3-Triazoles as inhibitors of indoleamine 2,3-dioxygenase 2 (IDO2).
Journal article

1,2,3-Triazoles as inhibitors of indoleamine 2,3-dioxygenase 2 (IDO2).

  • Röhrig UF Molecular Modeling Group, SIB Swiss Institute for Bioinformatics, CH-1015 Lausanne, Switzerland.
  • Majjigapu SR Molecular Modeling Group, SIB Swiss Institute for Bioinformatics, CH-1015 Lausanne, Switzerland; Laboratory of Glycochemistry and Asymmetric Synthesis, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.
  • Caldelari D Molecular Modeling Group, SIB Swiss Institute for Bioinformatics, CH-1015 Lausanne, Switzerland.
  • Dilek N Molecular Modeling Group, SIB Swiss Institute for Bioinformatics, CH-1015 Lausanne, Switzerland.
  • Reichenbach P Ludwig Center for Cancer Research of the University of Lausanne, CH-1066 Epalinges, Switzerland.
  • Ascencao K Molecular Modeling Group, SIB Swiss Institute for Bioinformatics, CH-1015 Lausanne, Switzerland.
  • Irving M Ludwig Center for Cancer Research of the University of Lausanne, CH-1066 Epalinges, Switzerland.
  • Coukos G Ludwig Center for Cancer Research of the University of Lausanne, CH-1066 Epalinges, Switzerland; Department of Oncology, University of Lausanne and Centre Hospitalier Universitaire Vaudois (CHUV), CH-1011 Lausanne, Switzerland.
  • Vogel P 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-1066 Epalinges, Switzerland.
  • Zoete V Molecular Modeling Group, SIB Swiss Institute for Bioinformatics, CH-1015 Lausanne, Switzerland. Electronic address: Vincent.Zoete@sib.swiss.
  • Michielin O Molecular Modeling Group, SIB Swiss Institute for Bioinformatics, CH-1015 Lausanne, Switzerland; Ludwig Center for Cancer Research of the University of Lausanne, CH-1066 Epalinges, Switzerland; Department of Oncology, University of Lausanne and Centre Hospitalier Universitaire Vaudois (CHUV), CH-1011 Lausanne, Switzerland. Electronic address: Olivier.Michielin@sib.swiss.
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  • 2016-07-30
Published in:
  • Bioorganic & medicinal chemistry letters. - 2016
Cancer immunotherapy
Cellular assays
Indoleamine 2,3-dioxygenase
Molecular modeling
Tryptophan metabolism
Catalytic Domain
Drug Design
Enzyme Activation
Enzyme Inhibitors
Humans
Indoleamine-Pyrrole 2,3,-Dioxygenase
Inhibitory Concentration 50
Molecular Weight
Triazoles
English Indoleamine 2,3-dioxygenase 2 (IDO2) is a potential therapeutic target for the treatment of diseases that involve immune escape such as cancer. In contrast to IDO1, only a very limited number of inhibitors have been described for IDO2 due to inherent difficulties in expressing and purifying a functionally active, soluble form of the enzyme. Starting from our previously discovered highly efficient 4-aryl-1,2,3-triazole IDO1 inhibitor scaffold, we used computational structure-based methods to design inhibitors of IDO2 which we then tested in cellular assays. Our approach yielded low molecular weight inhibitors of IDO2, the most active displaying an IC50 value of 51μM for mIDO2, and twofold selectivity over hIDO1. These compounds could be useful as molecular probes to investigate the biological role of IDO2, and could inspire the design of new IDO2 inhibitors.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/126150
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