NOVEL FLUORESCENT ESTROGEN RECEPTOR LIGAND BINDING ASSAY

点击翻译按钮获取中文摘要

The recent increased focus on estrogen receptor (ER) as a therapeutic target and the growing interest in the impact of environmental estrogens on human health has created an important need for improved assay methods to identify estrogen receptor ligands, particularly assay methods suited to high throughput screening formats. To address this need, PanVera will investigate development of homogenous in vitro fluorescence polarization assays for two human estrogen receptors, ERalpha and ERbeta. As a first step towards this goal, Phase I studies will develop fluorescent ligands for estrogen receptors by 1) synthesizing estrogen-fluorophore conjugates and characterizing their structure and chemical and photophysical properties, 2) evaluating the binding and fluorescence characteristics of the new conjugates with purified ERalpha and Erbeta, and optimizing fluorescence polarization assay conditions for those conjugates with the best properties, 3) validating the assay for high throughput screening applications by screening a panel of known ER ligands and test compounds from a pharmaceutical chemical collection, and comparing the relative binding affinities with those obtained using standard assay methods. Phase II studies will extend this technology to additional steroid hormone receptors. In Phase III, PanVera will commercialize this technology through its domestic and international distribution network, and pharmaceutical alliances. PROPOSED COMMERCIAL APPLICATION: The Phase I SBIR studies will result in development of a proprietary, homogenous fluorescence polarization assay for high throughput screening of estrogen receptor ligands. PanVera will commercialize these assays immediately through its domestic and international research products distribution network. Phase II studies will result in similar assays for other steroid hormone receptors, including androgen receptors and progesterone receptors. In Phase III, PanVera will continue and expand commercialization of each assay through its comprehensive distribution network and pharmaceutical alliances.