Dataset Information

Computational Approaches for the Discovery of GPER Targeting Compounds.

ABSTRACT: Estrogens exert a panel of biological activities mainly through the estrogen receptors ? and ?, which belong to the nuclear receptor superfamily. Diverse studies have shown that the G protein-coupled estrogen receptor 1 (GPER, previously known as GPR30) also mediates the multifaceted effects of estrogens in numerous pathophysiological events, including neurodegenerative, immune, metabolic, and cardiovascular disorders and the progression of different types of cancer. In particular, GPER is implicated in hormone-sensitive tumors, albeit diverse issues remain to be deeply investigated. As such, this receptor may represent an appealing target for therapeutics in different diseases. The yet unavailable complete GPER crystallographic structure, and its relatively low sequence similarity with the other members of the G protein-coupled receptor (GPCR) family, hamper the possibility to discover compounds able to modulate GPER activity. Consequently, a reliable molecular model of this receptor is required for the design of suitable ligands. To date, convergent approaches involving structure-based drug design and virtual ligand screening have led to the identification of several GPER selective ligands, thus providing important information regarding its mode of action and function. In this survey, we summarize results obtained through computer-aided techniques devoted to the assessment of GPER ligands toward their usefulness in innovative treatments of different diseases.

SUBMITTER: Grande F

PROVIDER: S-EPMC7417359 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Computational Approaches for the Discovery of GPER Targeting Compounds.

Grande Fedora F Occhiuzzi Maria A MA Lappano Rosamaria R Cirillo Francesca F Guzzi Rita R Garofalo Antonio A Jacquot Yves Y Maggiolini Marcello M Rizzuti Bruno B

Frontiers in endocrinology 20200804

Estrogens exert a panel of biological activities mainly through the estrogen receptors α and β, which belong to the nuclear receptor superfamily. Diverse studies have shown that the G protein-coupled estrogen receptor 1 (GPER, previously known as GPR30) also mediates the multifaceted effects of estrogens in numerous pathophysiological events, including neurodegenerative, immune, metabolic, and cardiovascular disorders and the progression of different types of cancer. In particular, GPER is impli ...[more]

PMID: 32849301

Similar Datasets

Project description:Hendra virus (HeV) belongs to the paramyxoviridae family of viruses which is associated with the respiratory distress, neurological illness, and potential fatality of the affected individuals. So far, no competitive approved therapeutic substance is available for HeV. For that reason, the current research work was conducted to propose some novel compounds, by adopting a Computer Aided Drug Discovery approach, which could be used to combat HeV. The G attachment Glycoprotein (Ggp) of HeV was selected to achieve the primary objective of this study, as this protein makes the entry of HeV possible in the host cells. Briefly, a library of 6000 antiviral compounds was screened for potential drug-like properties, followed by the molecular docking of short-listed compounds with the Protein Data Bank (PDB) structure of Ggp. Docked complexes of top two hits, having maximum binding affinities with the active sites of Ggp, were further considered for molecular dynamic simulations of 200 ns to elucidate the results of molecular docking analysis. MD simulations and Molecular Mechanics Energies combined with the Generalized Born and Surface Area (MMGBSA) or Poisson-Boltzmann and Surface Area (MMPBSA) revealed that both docked complexes are stable in nature. Furthermore, the same methodology was used between lead compounds and HeV Ggp in complex with its functional receptor in human, Ephrin-B2. Surprisingly, no major differences were found in the results, which demonstrates that our identified compounds can also perform their action even when the Ggp is attached to the Ephrin-B2 ligand. Therefore, in light of all of these results, we strongly suggest that compounds (S)-5-(benzylcarbamoyl)-1-(2-(4-methyl-2-phenylpiperazin-1-yl)-2-oxoethyl)-6-oxo-3,6-dihydropyridin-1-ium-3-ide and 5-(cyclohexylcarbamoyl)-1-(2-((2-(3-fluorophenyl)-2-methylpropyl)amino)-2-oxoethyl)-6-oxo-3,6-dihydropyridin-1-ium-3-ide could be considered as potential therapeutic agents against HeV; however, further in vitro and in vivo experiments are required to validate this study.

Dataset Information

Computational Approaches for the Discovery of GPER Targeting Compounds.

Publications

Computational Approaches for the Discovery of GPER Targeting Compounds.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets