%0 Journal Article %A Flynn, Autumn R. %A Mays, Suzanne G. %A A. Ortlund, Eric %A Jui, Nathan T. %D 2018 %T Development of Hybrid Phospholipid Mimics as Effective Agonists for Liver Receptor Homologue‑1 %U https://acs.figshare.com/articles/journal_contribution/Development_of_Hybrid_Phospholipid_Mimics_as_Effective_Agonists_for_Liver_Receptor_Homologue_1/7063742 %R 10.1021/acsmedchemlett.8b00361.s001 %2 https://acs.figshare.com/ndownloader/files/12988082 %K receptor Liver Receptor Homologue %K micromolar efficacy %K Effective Agonists %K ligand classes %K Hybrid Phospholipid Mimics %K drug target %K LRH %K hexahydropentalene compounds %K ligand binding pocket %X 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. %I ACS Publications