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-α, PPAR-δ, and PPAR-γ. 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.









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We thank Dr. Rémy D. Hoffmann, Accelrys SARL Paris, for screening the Derwent WDI database.
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Markt, P., Schuster, D., Kirchmair, J. et al. Pharmacophore modeling and parallel screening for PPAR ligands. J Comput Aided Mol Des 21, 575–590 (2007). https://doi.org/10.1007/s10822-007-9140-0
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DOI: https://doi.org/10.1007/s10822-007-9140-0