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

Details

Serval ID
serval:BIB_9DF2682ECDFF
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
1,2,3-Triazoles as inhibitors of indoleamine 2,3-dioxygenase 2 (IDO2).
Journal
Bioorganic & medicinal chemistry letters
Author(s)
Röhrig U.F., Majjigapu S.R., Caldelari D., Dilek N., Reichenbach P., Ascencao K., Irving M., Coukos G., Vogel P., Zoete V., Michielin O.
ISSN
1464-3405 (Electronic)
ISSN-L
0960-894X
Publication state
Published
Issued date
01/09/2016
Peer-reviewed
Oui
Volume
26
Number
17
Pages
4330-4333
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
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.

Keywords
Cancer immunotherapy, Cellular assays, Indoleamine 2,3-dioxygenase, Molecular modeling, Tryptophan metabolism
Pubmed
Web of science
Create date
05/08/2016 16:36
Last modification date
20/08/2019 15:04
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