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Updated: Feb 3, 2026

Quantifying Agonist Activity at G Protein-coupled Receptors
Published on: December 26, 2011
Development of Hybrid Phospholipid Mimics as Effective Agonists for Liver Receptor Homologue-1
Autumn R Flynn1, Suzanne G Mays1, Eric A Ortlund1
1Department of Chemistry, Department of Biochemistry, and Winship Cancer Institute, Emory University, Atlanta, Georgia 30322, United States.
Abstract:
The orphan nuclear receptor Liver Receptor Homologue-1 (LRH-1) is an emerging drug target for metabolic disorders. The most effective known LRH-1 modulators are phospholipids or synthetic hexahydropentalene compounds. While both classes have micromolar efficacy, they target different portions of the ligand binding pocket and activate LRH-1 through different mechanisms. Guided by crystallographic data, we combined aspects of both ligand classes into a single scaffold, resulting in the most potent and efficacious LRH-1 agonists to date.
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