ml8b00361_si_001.pdf (1002.85 kB)
Development of Hybrid Phospholipid Mimics as Effective Agonists for Liver Receptor Homologue‑1
journal contribution
posted on 2018-09-04, 00:00 authored by Autumn
R. Flynn, Suzanne G. Mays, Eric A. Ortlund, Nathan T. JuiThe
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.