title: Discovery of novel human histamine H4 receptor ligands by large-scale structure-based virtual screening.
abstract: A structure-based virtual screening (SBVS) was conducted on a ligand-supported homology model of the human histamine H4 receptor (hH4R). More than 8.7 million 3D structures derived from different vendor databases were investigated by docking to the hH4R binding site using FlexX. A total of 255 selected compounds were tested by radioligand binding assay and 16 of them possessed significant [(3)H]histamine displacement. Several novel scaffolds were identified that can be used to develop selective H4 ligands in the future. As far as we know, this is the first SBVS reported on H4R, representing one of the largest virtual screens validated by the biological evaluation of the virtual hits.
authors.affiliation: Gedeon Richter Plc, Budapest, Hungary.
authors.forename: Róbert
authors.initials: R
authors.lastname: Kiss
authors.forename: Béla
authors.initials: B
authors.lastname: Kiss
authors.forename: Arpád
authors.initials: A
authors.lastname: Könczöl
authors.forename: Ferenc
authors.initials: F
authors.lastname: Szalai
authors.forename: Ivett
authors.initials: I
authors.lastname: Jelinek
authors.forename: Valéria
authors.initials: V
authors.lastname: László
authors.forename: Béla
authors.initials: B
authors.lastname: Noszál
authors.forename: András
authors.initials: A
authors.lastname: Falus
authors.forename: György M
authors.initials: GM
authors.lastname: Keseru
mesh_terms: D001667:Binding, Competitive; D045744:Cell Line, Tumor; D016208:Databases, Factual; D006633:Histamine Antagonists / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D011869:Radioligand Assay; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism; D011968:Receptors, Histamine / Q000737:chemistry* / Q000378:metabolism; D000074040:Receptors, Histamine H4; D013329:Structure-Activity Relationship
chemical_list: C418607:HRH4 protein, human; D006633:Histamine Antagonists; D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4