title: Pharmacophore modeling for COX-1 and -2 inhibitors with LigandScout in comparison to Discovery Studio.
abstract: BACKGROUND
  Pharmacophore modeling has become an integrated tool in drug discovery. However, no prospective study compares the performance of the available software.
  
  
  METHODS
  The two widely used pharmacophore modeling and screening software programs Discovery Studio and LigandScout were used to generate, validate, and prospectively apply COX-1 and -2 models. Selected virtual hits were tested in cell-free enzymatic assays. The correct retrieval of active compounds was compared.
  
  
  RESULTS
  In the enzymatic testing, 10.5% of the tested hits for COX-2 and 6.6% of the predicted compounds for COX-1 were active. To directly compare the two models, both based on the same PDB entry, were selected for virtual screening. The two programs yielded vastly different hit lists, but both predicted active compounds.
  
  
  CONCLUSIONS
  To obtain a comprehensive selection of active compounds, more than one program should be used for modeling.
authors.affiliation: Computer-Aided Molecular Design Group & Center for Molecular Biosciences Innsbruck (CMBI), Institute of Pharmacy/Pharmaceutical Chemistry, University of Innsbruck, Innrain 80-82, A-6020 Innsbruck, Austria.
authors.forename: Veronika
authors.initials: V
authors.lastname: Temml
authors.forename: Teresa
authors.initials: T
authors.lastname: Kaserer
authors.forename: Zsofia
authors.initials: Z
authors.lastname: Kutil
authors.forename: Premysl
authors.initials: P
authors.lastname: Landa
authors.forename: Tomas
authors.initials: T
authors.lastname: Vanek
authors.forename: Daniela
authors.initials: D
authors.lastname: Schuster
mesh_terms: D001665:Binding Sites; D051545:Cyclooxygenase 1 / Q000737:chemistry* / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000737:chemistry* / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry* / Q000378:metabolism; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008024:Ligands; D062105:Molecular Docking Simulation; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D016861:Cyclooxygenase Inhibitors; D008024:Ligands; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2