Biomolecules & Therapeutics  https://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
Bin Xiao1,†, Dan-dan Li2,†, Ying Wang2, Eun La Kim2, Na Zhao1, Shang-Wu Jin3, Dong-Hao Bai3, Li-Dong Sun3,* and Jee H. Jung2,*
1Laboratory of Clinical Pharmacy, Ordos Central Hospital, Ordos School of Clinical Medicine, Inner Mongolia Medical University, Ordos 017000, China
2College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea
3The Fourth People’s Hospital of Ordos, Ordos 017000, China
*E-mail: 935194526@qq.com (Sun LD), jhjung@pusan.ac.kr (Jung JH)
Tel: +86-477-8185276 (Sun LD), +851-510-2803 (Jung JH)
Fax: +86-477-8185276 (Sun LD), +851-513-6754 (Jung JH)
The first two authors contributed equally to this work.
Received: January 11, 2021; Revised: March 26, 2021; Accepted: March 31, 2021; Published online: April 22, 2021.
© The Korean Society of Applied Pharmacology. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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 -β. These data indicated that parecoxib might be utilized as a partial PPAR-γ agonist for drug repositioning study.
Keywords: Parecoxib, In silico screening, PPAR-γ agonist, Adipogenesis


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