title: Pharmacophore modeling and parallel screening for PPAR ligands.
abstract: We describe the generation and validation of pharmacophore models for PPARs, as well as a large scale validation of the parallel screening approach by screening PPAR ligands against a large database of structure-based models. A large test set of 357 PPAR ligands was screened against 48 PPAR models to determine the best models for agonists of PPAR-alpha, PPAR-delta, and PPAR-gamma. Afterwards, a parallel screen was performed using the 357 PPAR ligands and 47 structure-based models for PPARs, which were integrated into a 1537 models comprising in-house pharmacophore database, to assess the enrichment of PPAR ligands within the PPAR hypotheses. For these purposes, we categorized the 1537 database models into 181 protein targets and developed a score that ranks the retrieved targets for each ligand. Thus, we tried to find out if the concept of parallel screening is able to predict the correct pharmacological target for a set of compounds. The PPAR target was ranked first more often than any other target. This confirms the ability of parallel screening to forecast the pharmacological active target for a set of compounds.
authors.affiliation: Department of Pharmaceutical Chemistry, Institute of Pharmacy and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innrain 52c, 6020 Innsbruck, Austria.
authors.forename: Patrick
authors.initials: P
authors.lastname: Markt
authors.forename: Daniela
authors.initials: D
authors.lastname: Schuster
authors.forename: Johannes
authors.initials: J
authors.lastname: Kirchmair
authors.forename: Christian
authors.initials: C
authors.lastname: Laggner
authors.forename: Thierry
authors.initials: T
authors.lastname: Langer
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D016208:Databases, Factual; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D008024:Ligands; D008958:Models, Molecular; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists* / Q000737:chemistry*
chemical_list: D008024:Ligands; D047492:Peroxisome Proliferator-Activated Receptors