Cyclooxygenase-2 Inhibitor Parecoxib Was Disclosed as a PPAR-γ Agonist by In Silico and In Vitro Assay
10.4062/biomolther.2021.008
- Author:
Bin XIAO
1
;
Dan-dan LI
;
Ying WANG
;
Eun La KIM
;
Na ZHAO
;
Shang-Wu JIN
;
Dong-Hao BAI
;
Li-Dong SUN
;
Jee H. JUNG
Author Information
1. Laboratory of Clinical Pharmacy, Ordos Central Hospital, Ordos School of Clinical Medicine, Inner Mongolia Medical University, Ordos 017000, China
- Publication Type:Original Article
- From:Biomolecules & Therapeutics
2021;29(5):519-526
- CountryRepublic of Korea
- Language:English
-
Abstract:
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.
