Cyclooxygenase-2 Inhibitor Parecoxib Was Disclosed as a PPAR-γ Agonist by In Silico and In Vitro Assay

Abstract

In a search for effective PPAR-gamma agonists, 110 clinical drugs were screened via molecular docking, and 9 drugs, including parecoxib, were selected for subsequent biological evaluation. Molecular docking of parecoxib to the ligand-binding domain of PPAR-gamma showed high binding affinity and relevant binding conformation compared with the PPAR-gamma ligand/antidiabetic drug rosiglitazone. Per the docking result, parecoxib showed the best PPAR-gamma transactivation in Ac2F rat liver cells. Further docking simulation and a luciferase assay suggested parecoxib would be a selective (and partial) PPAR-gamma agonist. PPAR-gamma activation by parecoxib induced adipocyte differentiation in 3T3-L1 murine preadipocytes. Parecoxib promoted adipogenesis in a dose-dependent manner and enhanced the expression of adipogenesis transcription factors PPAR-gamma, C/EBP alpha, and C/EBP beta. These data indicated that parecoxib might be utilized as a partial PPAR-gamma agonist for drug repositioning study.