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  • Novel scaffolds for modulation of NOD2 identified by pharmacophore-based virtual screening [Elektronski vir]
    Guzelj, Samo ; Tomašič, Tihomir ; Jakopin, Žiga
    Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) is an innate immune pattern recognition receptor responsible for the recognition of bacterial peptidoglycan fragments. Given its ... central role in the formation of innate and adaptive immune responses, NOD2 represents a valuable target for modulation with agonists and antagonists. A major challenge in the discovery of novel small-molecule NOD2 modulators is the lack of a co-crystallized complex with a ligand, which has limited previous progress to ligand-based design approaches and high-throughput screening campaigns. To that end, a hybrid docking and pharmacophore modeling approach was used to identify key interactions between NOD2 ligands and residues in the putative ligand-binding site. Following docking of previously reported NOD2 ligands to a homology model of human NOD2, a structure-based pharmacophore model was created and used to virtually screen a library of commercially available compounds. Two compounds, 1 and 3, identified as hits by the pharmacophore model, exhibited NOD2 antagonist activity and are the first small-molecule NOD2 modulators identified by virtual screening to date. The newly identified NOD2 antagonist scaffolds represent valuable starting points for further optimization.
    Source: Biomolecules [Elektronski vir]. - ISSN 2218-273X (Vol. 12, iss. 8, art. 1054, 2022, 17 str.)
    Type of material - e-article ; adult, serious
    Publish date - 2022
    Language - english
    COBISS.SI-ID - 117616387

    Link(s):

    https://www.mdpi.com/2218-273X/12/8/1054
    Repository of the University of Ljubljana – RUL
    DOI

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