title: A Novel Multi-step Virtual Screening for the Identification of Human and Mouse mPGES-1 Inhibitors.
abstract: We present here the development of a novel virtual screening protocol combining Structure-based and Ligand-based drug design approaches for the identification of mouse mPGES-1 inhibitors. We used the existing 3D structural data of the murine enzyme to hypothesize the inhibitors binding mode, which was the starting point for docking simulations, shape screening, and pharmacophore hypothesis screening. The protocol allowed the identification of 16 mouse mPGES-1 inhibitors with low micromolar activity, which, notably, also inhibit the human enzyme in the same concentration range. The inhibitors predicted binding mode is expected to be the base for the rational drug design of new potent dual species inhibitors of human and murine mPGES-1.
authors.affiliation: Angelini Research Center, Angelini S.p.A. P.le della Stazione, snc, I-00071 S. Palomba - Pomezia (RM) -, Italy . G.Corso@angelini.it.
authors.forename: G
authors.initials: G
authors.lastname: Corso
authors.affiliation: Angelini Research Center, Angelini S.p.A. P.le della Stazione, snc, I-00071 S. Palomba - Pomezia (RM) -, Italy.
authors.forename: M A
authors.initials: MA
authors.lastname: Alisi
authors.affiliation: Angelini Research Center, Angelini S.p.A. P.le della Stazione, snc, I-00071 S. Palomba - Pomezia (RM) -, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Cazzolla
authors.affiliation: Angelini Research Center, Angelini S.p.A. P.le della Stazione, snc, I-00071 S. Palomba - Pomezia (RM) -, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Coletta
authors.affiliation: Angelini Research Center, Angelini S.p.A. P.le della Stazione, snc, I-00071 S. Palomba - Pomezia (RM) -, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Furlotti
authors.affiliation: Angelini Research Center, Angelini S.p.A. P.le della Stazione, snc, I-00071 S. Palomba - Pomezia (RM) -, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Garofalo
authors.affiliation: Angelini Research Center, Angelini S.p.A. P.le della Stazione, snc, I-00071 S. Palomba - Pomezia (RM) -, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Mangano
authors.affiliation: Angelini Research Center, Angelini S.p.A. P.le della Stazione, snc, I-00071 S. Palomba - Pomezia (RM) -, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Mancini
authors.affiliation: Angelini Research Center, Angelini S.p.A. P.le della Stazione, snc, I-00071 S. Palomba - Pomezia (RM) -, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Vitiello
authors.affiliation: Angelini Research Center, Angelini S.p.A. P.le della Stazione, snc, I-00071 S. Palomba - Pomezia (RM) -, Italy.
authors.forename: Rosella
authors.initials: R
authors.lastname: Ombrato
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D051379:Mice; D008958:Models, Molecular; D062105:Molecular Docking Simulation / Q000379:methods; D000071876:Prostaglandin-E Synthases / Q000037:antagonists & inhibitors*; D011485:Protein Binding / Q000502:physiology; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D008024:Ligands; D000071876:Prostaglandin-E Synthases
keywords: homology modelling; human/mouse species specificity; mPGES-1; virtual screening; workflow development