title: A Virtual Screening Study for Lactate Dehydrogenase 5 Inhibitors by Using a Pharmacophore-based Approach.
abstract: Inhibitors of human lactate dehydrogenase 5 (hLDH5) are promising therapeutic agents against cancer. This enzyme is generally found to be overexpressed in most invasive cancer cells and is linked to their vitality especially under hypoxic conditions. In this study, with the aim of identifying new hLDH5 inhibitors, a receptor-based pharmacophore modeling approach has been tested and, in order to verify the reliability of the reported approach, the Gold and Platinum database from Asinex were filtered. The top-ranked compounds were experimentally tested for their hLDH5 inhibition activity and enzymatic assays revealed that, among the ten selected compounds, two proved to inhibit the enzyme activity with Ki values in the micromolar range (Ki =33.1-76.7 μM).
authors.affiliation: Department of Pharmacy, University of Pisa, Via Bonanno, 6 -, 56126, Pisa, Italy.
authors.forename: Tiziano
authors.initials: T
authors.lastname: Tuccinardi
authors.affiliation: Department of Pharmacy, University of Pisa, Via Bonanno, 6 -, 56126, Pisa, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Poli
authors.affiliation: Department of Pharmacy, University of Pisa, Via Bonanno, 6 -, 56126, Pisa, Italy.
authors.forename: Isacco
authors.initials: I
authors.lastname: Corchia
authors.affiliation: Department of Pharmacy, University of Pisa, Via Bonanno, 6 -, 56126, Pisa, Italy.
authors.forename: Carlotta
authors.initials: C
authors.lastname: Granchi
authors.affiliation: Department of Pharmacy, University of Pisa, Via Bonanno, 6 -, 56126, Pisa, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Lapillo
authors.affiliation: Department of Pharmacy, University of Pisa, Via Bonanno, 6 -, 56126, Pisa, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Macchia
authors.affiliation: Department of Pharmacy, University of Pisa, Via Bonanno, 6 -, 56126, Pisa, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Minutolo
authors.affiliation: Department of Pharmacy, University of Pisa, Via Bonanno, 6 -, 56126, Pisa, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Ortore
authors.affiliation: Department of Pharmacy, University of Pisa, Via Bonanno, 6 -, 56126, Pisa, Italy. adriano.martinelli@unipi.it.
authors.forename: Adriano
authors.initials: A
authors.lastname: Martinelli
mesh_terms: D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors*; D000080864:Lactate Dehydrogenase 5; D062105:Molecular Docking Simulation / Q000379:methods; D009369:Neoplasms / Q000188:drug therapy; D011485:Protein Binding / Q000502:physiology; D015203:Reproducibility of Results; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5
keywords: LDH5 inhibitors; docking; medicinal chemistry; receptor based pharmacophore; virtual screening