Rational design of 4-aryl-1,2,3-triazoles for indoleamine 2,3-dioxygenase 1 inhibition.

Details

Serval ID
serval:BIB_B5AF259B23AE
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Rational design of 4-aryl-1,2,3-triazoles for indoleamine 2,3-dioxygenase 1 inhibition.
Journal
Journal of Medicinal Chemistry
Author(s)
Röhrig U.F., Majjigapu S.R., Grosdidier A., Bron S., Stroobant V., Pilotte L., Colau D., Vogel P., Van den Eynde B.J., Zoete V., Michielin O.
ISSN
1520-4804 (Electronic)
ISSN-L
0022-2623
Publication state
Published
Issued date
2012
Peer-reviewed
Oui
Volume
55
Number
11
Pages
5270-5290
Language
english
Notes
Publication types: Journal Article
Abstract
Indoleamine 2,3-dioxygenase 1 (IDO1) is an important therapeutic target for the treatment of diseases such as cancer that involve pathological immune escape. Starting from the scaffold of our previously discovered IDO1 inhibitor 4-phenyl-1,2,3-triazole, we used computational structure-based methods to design more potent ligands. This approach yielded highly efficient low molecular weight inhibitors, the most active being of nanomolar potency both in an enzymatic and in a cellular assay, while showing no cellular toxicity and a high selectivity for IDO1 over tryptophan 2,3-dioxygenase (TDO). A quantitative structure-activity relationship based on the electrostatic ligand-protein interactions in the docked binding modes and on the quantum chemically derived charges of the triazole ring demonstrated a good explanatory power for the observed activities.
Pubmed
Web of science
Create date
22/07/2012 21:08
Last modification date
20/08/2019 15:24
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