scholarly journals Development of a Graphical User Interface Application to Identify Marginal and Potent Ligands for Estrogen Receptor Alpha

2019 ◽  
Vol 19 (2) ◽  
pp. 531 ◽  
Author(s):  
Nunung Yuniarti ◽  
Sudi Mungkasi ◽  
Sri Hartati Yuliani ◽  
Enade Perdana Istyastono
Keyword(s):  
Estrogen Receptor ◽  
User Interface ◽  
Graphical User Interface ◽  
Estrogen Receptor Alpha ◽  
Predictive Ability ◽  
In Vitro Test ◽  
Ligand Interaction ◽  
Qsar Analysis ◽  
Receptor Alpha

Employing ensemble Protein-Ligand Interaction Fingerprints (ensPLIF) as descriptors in post retrospective Structure-Based Virtual Screening (SBVS) campaigns Quantitative Structure-Activity Relationship (QSAR) analysis has been proven to significantly increase the predictive ability in the identification of potent ligands for estrogen receptor alpha (ERα). In the research presented in this article, similar approaches have been performed to construct and retrospectively validate an SBVS protocol to identify marginal ligands for ERα. Based on both validated SBVS protocols, a graphical-user-interface (GUI) application to identify if a compound is a non-, moderate or potent ligand for ERα was developed. The GUI application was subsequently used to virtually screen genistin, genistein, daidzin, and daidzein, followed by in vitro test employing a cytotoxic assay using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) method.

scholarly journals Computer-Aided Drug Repurposing: A Cyclooxygenase-2 Inhibitor Celecoxib as a Ligand for Estrogen Receptor Alpha

2015 ◽  
Vol 15 (3) ◽  
pp. 274-280 ◽  
Author(s):  
Enade Perdana Istyastono ◽  
Florentinus Dika Octa Riswanto ◽  
Sri Hartati Yuliani
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
In Silico ◽  
Estrogen Receptor Alpha ◽  
Cyclooxygenase 2 ◽  
Cytotoxic Activities ◽  
In Vitro Test ◽  
Receptor Alpha ◽  
Vitro Test

A cyclooxygenase-2 (COX-2) inhibitor celecoxib has been previously reported to have cytotoxic activities towards gastric, prostate, ovarian, colon and breast cancer cell lines. This article reports that the cytotoxic activities of celecoxib could be resulted from its activity as a potent ligand for estrogen receptor alpha (ERα). Aided by molecular docking simulations, an in silico test to examine whether celecoxib is a ligand for estrogen receptor alpha (ERα) was performed followed by in vitro test employing cytotoxic assay using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) method. The compound was extracted from Celebrex®. Measured by using UV spectrophotometric method at 255.5 nm, it was identified that the content of celecoxib was 102.15 mg/271.48 mg capsule content. The in silico test indicated that celecoxib is a potent ligand for ERα. This finding was confirmed experimentally by an in vitro test that celecoxib has a comparable activity as an ERα ligand to tamoxifen, a drug of choice for breast cancer treatment.

MP68-13 ESTROGEN RECEPTOR ALPHA PREVENTS BLADDER CANCER VIA INPP4B INHIBITED AKT PATHWAY IN VITRO AND IN VIVO

2015 ◽  
Vol 193 (4S) ◽  
Author(s):  
Chiuan-Ren Yeh ◽  
Iawen Hsu ◽  
Hiroshi Miyamoto ◽  
Xue-Ru Wu ◽  
Chawnshang Chang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Estrogen Receptor ◽  
Estrogen Receptor Alpha ◽  
Akt Pathway ◽  
Receptor Alpha

Membrane and Nuclear Estrogen Receptor Alpha Actions: From Tissue Specificity to Medical Implications

2017 ◽  
Vol 97 (3) ◽  
pp. 1045-1087 ◽  
Author(s):  
Jean-Francois Arnal ◽  
Françoise Lenfant ◽  
Raphaël Metivier ◽  
Gilles Flouriot ◽  
Daniel Henrion ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptor Alpha ◽  
Reproductive Tract ◽  
Vascular System ◽  
Physiological Role ◽  
Receptor Alpha ◽  
Nuclear Signaling ◽  
Nuclear Estrogen Receptor

Estrogen receptor alpha (ERα) has been recognized now for several decades as playing a key role in reproduction and exerting functions in numerous nonreproductive tissues. In this review, we attempt to summarize the in vitro studies that are the basis of our current understanding of the mechanisms of action of ERα as a nuclear receptor and the key roles played by its two activation functions (AFs) in its transcriptional activities. We then depict the consequences of the selective inactivation of these AFs in mouse models, focusing on the prominent roles played by ERα in the reproductive tract and in the vascular system. Evidence has accumulated over the two last decades that ERα is also associated with the plasma membrane and activates non-nuclear signaling from this site. These rapid/nongenomic/membrane-initiated steroid signals (MISS) have been characterized in a variety of cell lines, and in particular in endothelial cells. The development of selective pharmacological tools that specifically activate MISS and the generation of mice expressing an ERα protein impeded for membrane localization have begun to unravel the physiological role of MISS in vivo. Finally, we discuss novel perspectives for the design of tissue-selective ER modulators based on the integration of the physiological and pathophysiological roles of MISS actions of estrogens.

scholarly journals BINARY QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP ANALYSIS IN RETROSPECTIVE STRUCTURE-BASED VIRTUAL SCREENING CAMPAIGNS TARGETING ESTROGEN RECEPTOR ALPHA

2017 ◽  
Vol 10 (12) ◽  
pp. 206 ◽  
Author(s):  
Enade Perdana Istyastono ◽  
Nunung Yuniarti ◽  
Maywan Hariono ◽  
Sri Hartati Yuliani ◽  
Florentinus Dika Octa Riswanto
Keyword(s):  
Estrogen Receptor ◽  
Molecular Docking ◽  
Estrogen Receptor Alpha ◽  
Quantitative Structure Activity Relationship ◽  
Quantitative Structure ◽  
Qsar Analysis ◽  
Receptor Alpha ◽  
Structure Activity ◽  
Binary Qsar ◽  
F Measure

  Objective: The objective of this study is to construct predictive unbiased structure-based virtual screening (SBVS) protocols to identify potent ligands for estrogen receptor alpha by combining molecular docking, protein-ligand interaction fingerprinting (PLIF), and binary quantitative structure-activity relationship (QSAR) analysis using recursive partition and regression tree method.Methods: Employing the enhanced version of a directory of useful decoys, SBVS protocols using molecular docking simulations, and PLIF were constructed and retrospectively validated. To avoid bias, SMILES format of the compounds was used. The predictive abilities of the SBVS protocols were then compared based on the enrichment factor (EF) and the F-measure values.Results: The SBVS protocols resulted in this research were SBVS_1 (employing docking scores of the best pose on every compound to rank the results and selecting compounds within 1% false positives as positive), SBVS_2 (employing decision tree resulted from the binary QSAR analysis using docking scores and PLIF bitstrings of the best pose of every compound as descriptors), and SBVS_3 (employing decision tree resulted from the binary QSAR analysis using ensemble PLIF of the selected poses from optimized docking score as the cutoff). The EF values of SBVS_1, SBVS_2, and SBVS_3 are 28.315, 576.084, and 713.472, respectively, while their F-measure values are 0.310, 0.573, and 0.769, respectively.Conclusion: Highly predictive unbiased SBVS protocols to identify potent estrogen receptor alpha ligands were constructed. Further application in prospective screening is therefore highly suggested.

scholarly journals Expression of aromatase and estrogen receptor alpha in chondrosarcoma, but no beneficial effect of inhibiting estrogen signaling both in vitro and in vivo

2011 ◽  
Vol 1 (1) ◽  
pp. 5 ◽  
Author(s):  
Danielle Meijer ◽  
Hans Gelderblom ◽  
Marcel Karperien ◽  
Anne-Marie Cleton-Jansen ◽  
Pancras CW Hogendoorn ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Beneficial Effect ◽  
Estrogen Receptor Alpha ◽  
Estrogen Signaling ◽  
Receptor Alpha

scholarly journals Cross-talk between Stat5b and estrogen receptor-alpha and -beta in mammary epithelial cells

2001 ◽  
Vol 27 (1) ◽  
pp. 93-106 ◽  
Author(s):  
L Bjornstrom ◽  
E Kilic ◽  
M Norman ◽  
MG Parker ◽  
M Sjoberg
Keyword(s):  
Estrogen Receptor ◽  
Cross Talk ◽  
Estrogen Receptor Alpha ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Epithelial Cell Line ◽  
Receptor Alpha ◽  
Cell Extracts ◽  
C Terminus

Both 17beta-estradiol and prolactin play important roles in the mammary gland, raising the possibility of functional cross-talk between the two signaling pathways. Here, we demonstrate that estrogen receptor-alpha (ERalpha) and -beta (ERbeta) are both able to potentiate transcription from a Stat5-responsive promoter when activated by prolactin. Potentiation was observed not only in the presence of 17beta-estradiol, but also in the presence of anti-estrogens such as tamoxifen and ICI 182,780. The magnitude of the response was dependent on cell-type: in the HC11 mouse mammary epithelial cell line ERbeta potentiates transcription efficiently whereas ERalpha showed low activity. Conversely, in COS-7 cells, both estrogen receptors were active. We show that activation domains in the N-terminus (AF-1) and the C-terminus (AF-2) of the ERs are dispensable for potentiation. The effects are dependent on the presence of an intact DNA-binding/hinge domain, which we show is capable of interacting with Stat5b in vitro and in HC11 cell extracts. We conclude that ERalpha and ERbeta act as coactivators for Stat5b through a mechanism which is independent of AF-1 and AF-2.

scholarly journals Estrogen Receptor Alpha Expression in Podocytes Mediates Protection against Apoptosis In-Vitro and In-Vivo

PLoS ONE ◽  
2011 ◽  
Vol 6 (11) ◽  
pp. e27457 ◽  
Author(s):  
Sebastian Kummer ◽  
Stefanie Jeruschke ◽  
Lara Vanessa Wegerich ◽  
Andrea Peters ◽  
Petra Lehmann ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptor Alpha ◽  
Receptor Alpha
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