Open AccessCyclooxygenase-2 Inhibitor Parecoxib Was Disclosed as a PPAR-γ Agonist by In Silico and In Vitro Assay
Author(s) -
Bin Xiao,
Dandan Li,
Ying Wang,
Eun La Kim,
Na Zhao,
Shang-Wu Jin,
Dong-Hao Bai,
Lidong Sun,
Jee H. Jung
Publication year - 2021
Publication title -
biomolecules and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.977
H-Index - 36
eISSN - 2005-4483
pISSN - 1976-9148
DOI - 10.4062/biomolther.2021.008
Subject(s) - parecoxib , transactivation , agonist , adipogenesis , rosiglitazone , pharmacology , peroxisome proliferator activated receptor , docking (animal) , pioglitazone , in silico , in vitro , chemistry , luciferase , receptor , transcription factor , medicine , biochemistry , endocrinology , transfection , gene , type 2 diabetes , nursing , diabetes mellitus , analgesic
In a search for effective PPAR-γ 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-γ showed high binding affinity and relevant binding conformation compared with the PPAR-γ ligand/antidiabetic drug rosiglitazone. Per the docking result, parecoxib showed the best PPAR-γ transactivation in Ac2F rat liver cells. Further docking simulation and a luciferase assay suggested parecoxib would be a selective (and partial) PPAR-γ agonist. PPAR-γ 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-γ, C/EBPα, and C/EBPβ. These data indicated that parecoxib might be utilized as a partial PPAR-γ agonist for drug repositioning study.