Discovery of new nanomolar peroxisome proliferator-activated receptor γ activators via elaborate ligand-based modeling

► Eighty-eight diverse PPARγ activators were modeled by a combination of pharmacophore and QSAR analyses. ► The resulting models were validated by ROC curves and against an external list of compounds. ► Optimal models were used as 3D search queries against the NCI list of compounds. ► Three hits illustrated nanomolar bioactivation of PPARγ.