| Autor: |
Peekhaus, Norbert T., Ferrer, Marc, Chang, Tina, Kornienko, Oleg, Schneeweis, Jonathan E., Smith, Todd S., Hoffman, Ira, Mitnaul, Lyndon J., Chin, Jayne, Fischer, Paul A., Blizzard, Tim A., Birzin, Elizabeth T., Chan, Wanda, Inglese, James, Strulovici, Berta, Rohrer, Susan P., Schaeffer, James M. |
| Zdroj: |
Assay and Drug Development Technologies; December 2003, Vol. 1 Issue: 6 p789-800, 12p |
| Abstrakt: |
Estrogen action is mediated via two estrogen receptor (ER) subtypes, ERαand ERβ. Selective ER modulators with balanced high affinity for ERαand ERβhave been developed as therapeutics for the treatment of a variety of diseases, including hormone-responsive breast cancer and osteoporosis. Recent data based primarily on the evaluation of ER-knockout mice have revealed that ERαand ERβmay regulate separate and distinct biological processes. The identification of ERβspecific ligands could further enhance our understanding of ERβbiology. In addition, compounds targeting ERβmay prove useful as therapeutic agents with activity profiles distinguishable from that of estradiol. To discover novel selective ligands for ERβ, we developed and characterized a cell-based Gal4-ERββ-lactamase reporter gene assay (GERTA) in CHO cells for the ligand-induced activation of the human ERβ. The sensitivity and selectivity of this assay were found to be comparable to those of an ER ligand-binding assay. The assay was optimized for screening in an ultra high throughput 3,456-well nanoplate format and was successfully used to screen a large compound collection for ERβagonists. Compounds identified in a primary screen were tested in an in vitroligand-binding assay to characterize further the selectivity and potency for ERβ. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
