Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Cyclooxygenase-2 Inhibitor Parecoxib Was Disclosed as a PPAR-γ Agonist by In Silico and In Vitro Assay

  • Xiao, Bin (Laboratory of Clinical Pharmacy, Ordos Central Hospital, Ordos School of Clinical Medicine, Inner Mongolia Medical University) ;
  • Li, Dan-dan (College of Pharmacy, Pusan National University) ;
  • Wang, Ying (College of Pharmacy, Pusan National University) ;
  • Kim, Eun La (College of Pharmacy, Pusan National University) ;
  • Zhao, Na (Laboratory of Clinical Pharmacy, Ordos Central Hospital, Ordos School of Clinical Medicine, Inner Mongolia Medical University) ;
  • Jin, Shang-Wu (The Fourth People's Hospital of Ordos) ;
  • Bai, Dong-Hao (The Fourth People's Hospital of Ordos) ;
  • Sun, Li-Dong (The Fourth People's Hospital of Ordos) ;
  • Jung, Jee H. (College of Pharmacy, Pusan National University)
  • Received : 2021.01.11
  • Accepted : 2021.03.31
  • Published : 2021.09.01
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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.

Keywords

Acknowledgement

This research was supported by a 2-year grant from Pusan National University. We thank Hye Lim Byun and Sunwoo Yu for their sincere assistance in molecular docking calculations.

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