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http://dx.doi.org/10.4062/biomolther.2021.008

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)
Publication Information
Biomolecules & Therapeutics / v.29, no.5, 2021 , pp. 519-526 More about this Journal
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
Parecoxib; In silico screening; PPAR-${\gamma}$ agonist; Adipogenesis;
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