PMID- 27469130
OWN - NLM
STAT- MEDLINE
DCOM- 20170829
LR  - 20171122
IS  - 1464-3405 (Electronic)
IS  - 0960-894X (Linking)
VI  - 26
IP  - 17
DP  - 2016 Sep 1
TI  - 1,2,3-Triazoles as inhibitors of indoleamine 2,3-dioxygenase 2 (IDO2).
PG  - 4330-3
LID - S0960-894X(16)30744-2 [pii]
LID - 10.1016/j.bmcl.2016.07.031 [doi]
AB  - 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 51muM 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.
CI  - Copyright (c) 2016 Elsevier Ltd. All rights reserved.
FAU - Rohrig, Ute F
AU  - Rohrig UF
AD  - Molecular Modeling Group, SIB Swiss Institute for Bioinformatics, CH-1015 
      Lausanne, Switzerland.
FAU - Majjigapu, Somi Reddy
AU  - Majjigapu SR
AD  - Molecular Modeling Group, SIB Swiss Institute for Bioinformatics, CH-1015 
      Lausanne, Switzerland; Laboratory of Glycochemistry and Asymmetric Synthesis, 
      Ecole Polytechnique Federale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.
FAU - Caldelari, Daniela
AU  - Caldelari D
AD  - Molecular Modeling Group, SIB Swiss Institute for Bioinformatics, CH-1015 
      Lausanne, Switzerland.
FAU - Dilek, Nahzli
AU  - Dilek N
AD  - Molecular Modeling Group, SIB Swiss Institute for Bioinformatics, CH-1015 
      Lausanne, Switzerland.
FAU - Reichenbach, Patrick
AU  - Reichenbach P
AD  - Ludwig Center for Cancer Research of the University of Lausanne, CH-1066 
      Epalinges, Switzerland.
FAU - Ascencao, Kelly
AU  - Ascencao K
AD  - Molecular Modeling Group, SIB Swiss Institute for Bioinformatics, CH-1015 
      Lausanne, Switzerland.
FAU - Irving, Melita
AU  - Irving M
AD  - Ludwig Center for Cancer Research of the University of Lausanne, CH-1066 
      Epalinges, Switzerland.
FAU - Coukos, George
AU  - Coukos G
AD  - 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.
FAU - Vogel, Pierre
AU  - Vogel P
AD  - Laboratory of Glycochemistry and Asymmetric Synthesis, Ecole Polytechnique 
      Federale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland; Ludwig Center for 
      Cancer Research of the University of Lausanne, CH-1066 Epalinges, Switzerland.
FAU - Zoete, Vincent
AU  - Zoete V
AD  - Molecular Modeling Group, SIB Swiss Institute for Bioinformatics, CH-1015 
      Lausanne, Switzerland. Electronic address: Vincent.Zoete@sib.swiss.
FAU - Michielin, Olivier
AU  - Michielin O
AD  - 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.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160716
PL  - England
TA  - Bioorg Med Chem Lett
JT  - Bioorganic & medicinal chemistry letters
JID - 9107377
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase)
RN  - 0 (Triazoles)
SB  - IM
MH  - Catalytic Domain
MH  - Drug Design
MH  - Enzyme Activation/drug effects
MH  - Enzyme Inhibitors/chemical synthesis/chemistry/pharmacology
MH  - Humans
MH  - Indoleamine-Pyrrole 2,3,-Dioxygenase/*antagonists & inhibitors
MH  - Inhibitory Concentration 50
MH  - Molecular Weight
MH  - Triazoles/*chemical synthesis/chemistry/pharmacology
OTO - NOTNLM
OT  - Cancer immunotherapy
OT  - Cellular assays
OT  - Indoleamine 2,3-dioxygenase
OT  - Molecular modeling
OT  - Tryptophan metabolism
EDAT- 2016/07/30 06:00
MHDA- 2017/08/30 06:00
CRDT- 2016/07/30 06:00
PHST- 2016/06/23 00:00 [received]
PHST- 2016/07/13 00:00 [revised]
PHST- 2016/07/14 00:00 [accepted]
PHST- 2016/07/30 06:00 [entrez]
PHST- 2016/07/30 06:00 [pubmed]
PHST- 2017/08/30 06:00 [medline]
AID - S0960-894X(16)30744-2 [pii]
AID - 10.1016/j.bmcl.2016.07.031 [doi]
PST - ppublish
SO  - Bioorg Med Chem Lett. 2016 Sep 1;26(17):4330-3. doi: 10.1016/j.bmcl.2016.07.031. 
      Epub 2016 Jul 16.