Cyclooxygenase-2 Inhibitor Parecoxib Was Disclosed as a PPAR-γ Agonist by In Silico and In Vitro Assay
| Autor: | Dan-Dan Li, Dong-Hao Bai, Jee H. Jung, Bin Xiao, Ying Wang, Na Zhao, Shang-Wu Jin, Li-Dong Sun, Eun La Kim |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Pharmacology
Agonist Adipogenesis biology Chemistry medicine.drug_class Ligand (biochemistry) Biochemistry Transactivation In silico screening Docking (molecular) Parecoxib Drug Discovery PPAR-γ agonist medicine biology.protein Molecular Medicine lipids (amino acids peptides and proteins) Original Article Cyclooxygenase Rosiglitazone medicine.drug |
| Zdroj: | Biomolecules & Therapeutics |
| ISSN: | 2005-4483 1976-9148 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|