title: A virtual screening study of the 18 kDa translocator protein using pharmacophore models combined with 3D-QSAR studies.
abstract: In the present study, we considered various pharmacophore hypotheses for TSPO ligands and an optimal one was selected on the basis of 3D-QSAR studies. This hypothesis was used in a ligand-based virtual screening study on the Maybridge database with the aim of identifying new TSPO ligands. Binding assays revealed that all selected compounds displayed TSPO affinity at 10 microM, and among them two compounds exhibited sub-micromolar K(i) values. These results validated our applied methodologies, and the two compounds with sub-micromolar affinity could be used as interesting leads for the development of new active TSPO ligands.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Pisa via Bonanno 6, 56126 Pisa (Italy). tuccinardi@farm.unipi.it
authors.forename: Tiziano
authors.initials: T
authors.lastname: Tuccinardi
authors.forename: Sabrina
authors.initials: S
authors.lastname: Taliani
authors.forename: Marusca
authors.initials: M
authors.lastname: Bellandi
authors.forename: Federico
authors.initials: F
authors.lastname: Da Settimo
authors.forename: Eleonora
authors.initials: E
authors.lastname: Da Pozzo
authors.forename: Claudia
authors.initials: C
authors.lastname: Martini
authors.forename: Adriano
authors.initials: A
authors.lastname: Martinelli
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D055808:Drug Discovery; D006801:Humans; D008024:Ligands; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D018079:Receptors, GABA / Q000737:chemistry* / Q000378:metabolism; D012984:Software
chemical_list: D008024:Ligands; D018079:Receptors, GABA; C499229:TSPO protein, human