Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document
Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

Title: A Computational-Based Approach to Identify Estrogen Receptor α/β Heterodimer Selective Ligands.

Authors: Coriano, Carlos G; Liu, Fabao; Sievers, Chelsie K; Liang, Muxuan; Wang, Yidan; Lim, Yoongho; Yu, Menggang; Xu, Wei

Published In Mol Pharmacol, (2018 03)

Abstract: The biologic effects of estrogens are transduced by two estrogen receptors (ERs), ERα and ERβ, which function in dimer forms. The ERα/α homodimer promotes and the ERβ/β inhibits estrogen-dependent growth of mammary epithelial cells; the functions of ERα/β heterodimers remain elusive. Using compounds that promote ERα/β heterodimerization, we have previously shown that ERα/β heterodimers appeared to inhibit tumor cell growth and migration in vitro. Further dissection of ERα/β heterodimer functions was hampered by the lack of ERα/β heterodimer-specific ligands. Herein, we report a multistep workflow to identify the selective ERα/β heterodimer-inducing compound. Phytoestrogenic compounds were first screened for ER transcriptional activity using reporter assays and ER dimerization preference using a bioluminescence resonance energy transfer assay. The top hits were subjected to in silico modeling to identify the pharmacophore that confers ERα/β heterodimer specificity. The pharmacophore encompassing seven features that are potentially important for the formation of the ERα/β heterodimer was retrieved and subsequently used for virtual screening of large chemical libraries. Four chemical compounds were identified that selectively induce ERα/β heterodimers over their respective homodimers. Such ligands will become unique tools to reveal the functional insights of ERα/β heterodimers.

PubMed ID: 29295894 Exiting the NIEHS site

MeSH Terms: Bioluminescence Resonance Energy Transfer Techniques; Cell Line; Computational Biology/methods*; Drug Evaluation, Preclinical; Estrogen Receptor alpha/chemistry; Estrogen Receptor alpha/metabolism*; Estrogen Receptor beta/chemistry; Estrogen Receptor beta/metabolism*; Female; HEK293 Cells; Humans; Ligands; MCF-7 Cells; Mammary Glands, Human/cytology*; Mammary Glands, Human/metabolism; Models, Molecular; Phytoestrogens/chemistry; Phytoestrogens/pharmacology*; Protein Multimerization

Back
to Top