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Published on: February 20, 2018
Identification of novel agonists and antagonists of the ecdysone receptor by virtual screening
Xueping Hu1, Bin Yin1, Kaat Cappelle2
1Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, China.
Abstract:
Insect growth is regulated by the steroid hormone 20-hydroxyecdysone (20E), which works via the ecdysone receptor (EcR). To identify biologically active and novel ecdysone agonists/antagonists, ligand/structure-based virtual screening combined with pharmacophore modeling and molecular docking was performed to identify novel nonsteroidal lead compounds. Nine molecules were screened and selected for an in vitro cell-based reporter bioassay. The results showed that VS-006 and VS-009 exhibited antagonistic activity in S2 cells, whereas only VS-006 exhibited antagonistic activity in Bm5 cells. Molecular dynamic simulation of VS-006 complexed with the ligand binding domain of EcR validated the binding stability of VS-006 and highlighted the key residues for further lead optimization.
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