Pharmacophore model construction and docking study analysis of novel IDO inhibitors
ZHANG Shiying
ZHANG Anli
LIU Yating
SUN Bin
Abstract：Indoleamine 2,3-dioxygenase(IDO),a key enzyme in tryptophan metabolism,mediates im-mune escape by degrading tryptophan and promoting the accumulation of toxic kynurenine metabolites in the tumor microenvironment.This process induces T-cell apoptosis and immune tolerance.Although IDO inhibitors have demonstrated promising antitumor immunomodulatory potential in preclinical studies,their precise target binding modes remain unclear,hindering the development of highly effective inhibitors.In this study,eight IDO inhibitors with diverse core scaffold structures were selected to construct a common-feature pharmacophore model.The core pharmacophore consists of two hydrogen bond acceptors and two hydrophobic features.Furthermore,molecular dynamics simulations and docking studies were employed to elucidate key interaction patterns between representative IDO inhibitors and the receptor's active site,thereby clarifying their structure-activity relationships.These findings provide important strategic guid-ance for the development of novel and potent IDO inhibitors.
Keywords：indoleamine 23-dioxygenasepharmacophoremolecular dockingstructure-activity relation-ship
Publication Date：2026-04-25
Online Publishing Date：2026-08-28(First online date of this platform, not the publication date of the document)
Pages：7( 300-306 )