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Development of Hybrid Phospholipid Mimics as Effective Agonists for Liver Receptor Homologue‑1

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journal contribution
posted on 04.09.2018, 00:00 by Autumn R. Flynn, Suzanne G. Mays, Eric A. Ortlund, Nathan T. Jui
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.