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Updated: Jul 9, 2026

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay
Published on: December 19, 2018
On the intractability of estrogen-related receptor alpha as a target for activation by small molecules
Stephen M Hyatt1, Elizabeth L Lockamy, Rebecca A Stein
1Molecular Discovery Research Branch, GlaxoSmithKline, Research Triangle Park, NC 27709, USA.
Abstract:
The estrogen-related receptor alpha (ERRalpha) is a potential target for activation in the treatment of metabolic disease. To date, no small-molecule agonists of ERRalpha have been identified despite several high-throughput screening campaigns. We describe the synthesis and profiling of a small array of compounds designed on the basis of a previously reported agonist-bound crystal structure of the closely related receptor ERRgamma. The results suggest that ERRalpha may be intractable as a direct target for pharmacologic activation.
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