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KMID : 0606920210290050519
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Biomolecules & Therapeutics
2021 Volume.29 No. 5 p.519 ~ p.526
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Cyclooxygenase-2 Inhibitor Parecoxib Was Disclosed as a PPAR-γ Agonist by In Silico and In Vitro Assay
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Xiao Bin
Li Dan-Dan
Wang Ying
Kim Eun-La
Zhao Na
Jin Shang-Wu
Bai Dong-Hao
Sun Li-Dong
Jung Jee-H.
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Abstract
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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.
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KEYWORD
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Parecoxib, In silico screening, PPAR-γ agonist, Adipogenesis
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