20.500.12556/RUL-138680 Novel scaffolds for modulation of NOD2 identified by pharmacophore-based virtual screening 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. antagonist homology modeling NOD2 Nucleotide-binding oligomerization pharmacophore modeling virtual screening antagonisti modeliranje homologije NOD2 oligomerizacija ki veže nukleotide modeliranje farmakoforja virtualno rešetanje true false false Angleški jezik Slovenski jezik Neznano 2022-08-09 11:41:03 2022-08-09 11:41:08 2025-08-08 13:21:22 0000-00-00 00:00:00 2022 0 0 17 str. iss. 8, art. 1054 Vol. 12 2022 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 2022-01-01 615.4:54:616-006 2218-273X 10.3390/biom12081054 117616387 https://www.mdpi.com/2218-273X/12/8/1054 1 2a502a38-1937-11ed-8aca-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=159152 https://www.mdpi.com/2218-273X/12/8/1054 1 1c1aa137-17c7-11ed-8aca-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=159076 biomolecules-12-01054.pdf biomolecules-12-01054.pdf 1 F226A94A9A0B4F7A80AFB676134B32DA 7045ba33c56ee15a1c4047ca5f7c6820a7b3082c250baefd8d6e1f1eb8427686 f47c20a7-17c7-11ed-8aca-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=159077 Fakulteta za farmacijo 0 0 0