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

Détails

ID Serval
serval:BIB_B5AF259B23AE
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Rational design of 4-aryl-1,2,3-triazoles for indoleamine 2,3-dioxygenase 1 inhibition.
Périodique
Journal of Medicinal Chemistry
Auteur⸱e⸱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
Statut éditorial
Publié
Date de publication
2012
Peer-reviewed
Oui
Volume
55
Numéro
11
Pages
5270-5290
Langue
anglais
Notes
Publication types: Journal Article
Résumé
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
Création de la notice
22/07/2012 21:08
Dernière modification de la notice
20/08/2019 15:24
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