10.1021/acsmedchemlett.8b00361.s001 Autumn R. Flynn Autumn R. Flynn Suzanne G. Mays Suzanne G. Mays Eric A. Ortlund Eric A. Ortlund Nathan T. Jui Nathan T. Jui Development of Hybrid Phospholipid Mimics as Effective Agonists for Liver Receptor Homologue‑1 American Chemical Society 2018 receptor Liver Receptor Homologue micromolar efficacy Effective Agonists ligand classes Hybrid Phospholipid Mimics drug target LRH hexahydropentalene compounds ligand binding pocket 2018-09-04 00:00:00 Journal contribution https://acs.figshare.com/articles/journal_contribution/Development_of_Hybrid_Phospholipid_Mimics_as_Effective_Agonists_for_Liver_Receptor_Homologue_1/7063742 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.