Profiling of the Tox21 10K compound library for agonists and antagonists of the estrogen receptor alpha signaling pathway.

Article Details

Citation

Huang R, Sakamuru S, Martin MT, Reif DM, Judson RS, Houck KA, Casey W, Hsieh JH, Shockley KR, Ceger P, Fostel J, Witt KL, Tong W, Rotroff DM, Zhao T, Shinn P, Simeonov A, Dix DJ, Austin CP, Kavlock RJ, Tice RR, Xia M

Profiling of the Tox21 10K compound library for agonists and antagonists of the estrogen receptor alpha signaling pathway.

Sci Rep. 2014 Jul 11;4:5664. doi: 10.1038/srep05664.

PubMed ID
25012808 [ View in PubMed
]
Abstract

The U.S. Tox21 program has screened a library of approximately 10,000 (10K) environmental chemicals and drugs in three independent runs for estrogen receptor alpha (ERalpha) agonist and antagonist activity using two types of ER reporter gene cell lines, one with an endogenous full length ERalpha (ER-luc; BG1 cell line) and the other with a transfected partial receptor consisting of the ligand binding domain (ER-bla; ERalpha beta-lactamase cell line), in a quantitative high-throughput screening (qHTS) format. The ability of the two assays to correctly identify ERalpha agonists and antagonists was evaluated using a set of 39 reference compounds with known ERalpha activity. Although both assays demonstrated adequate (i.e. >80%) predictivity, the ER-luc assay was more sensitive and the ER-bla assay more specific. The qHTS assay results were compared with results from previously published ERalpha binding assay data and showed >80% consistency. Actives identified from both the ER-bla and ER-luc assays were analyzed for structure-activity relationships (SARs) revealing known and potentially novel ERalpha active structure classes. The results demonstrate the feasibility of qHTS to identify environmental chemicals with the potential to interact with the ERalpha signaling pathway and the two different assay formats improve the confidence in correctly identifying these chemicals.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
MethyltestosteroneEstrogen receptor alphaProteinHumans
Unknown
Not AvailableDetails