title: 2D QSAR of PPARgamma agonist binding and transactivation.
abstract: Multilinear QSAR models are developed for the largest and most diverse set of PPARgamma agonists treated hitherto. Binding of these small molecules to the human nuclear receptor PPARgamma is described by models that are built on simple 2D molecular descriptors and nevertheless are of good quality and predictive power (e.g., 144 compounds, 10 descriptors, r2=0.79, r2(cv)=0.76). The models presented are thoroughly validated by crossvalidation, randomization experiments, bootstrapping, and training set/test set partitioning. They may therefore be helpful in the design of new antidiabetic drug candidates. For gene transactivation, the functional activity of the agonists, a corresponding model for a similarly diverse compound set is of somewhat lower statistical quality.
authors.affiliation: Biocenter, University of Basel, Klingelbergstrasse 50-70, CH-4056 Basel, Switzerland. christoph.ruecker@unibas.ch
authors.forename: Christoph
authors.initials: C
authors.lastname: Rücker
authors.forename: Marco
authors.initials: M
authors.lastname: Scarsi
authors.forename: Markus
authors.initials: M
authors.lastname: Meringer
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D015195:Drug Design; D005227:Fatty Acids / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology; D008024:Ligands; D015394:Molecular Structure; D047495:PPAR gamma / Q000819:agonists* / Q000737:chemistry / Q000235:genetics*; D021281:Quantitative Structure-Activity Relationship; D045162:Thiazolidinediones / Q000737:chemistry / Q000494:pharmacology; D015533:Transcriptional Activation / Q000187:drug effects; D014443:Tyrosine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology
chemical_list: D005227:Fatty Acids; D007211:Indoles; D008024:Ligands; D047495:PPAR gamma; D045162:Thiazolidinediones; D014443:Tyrosine