The Medicinal Chemistry of Liver X Receptor (LXR) Modulators

LXRs
have been of interest as targets for the treatment of atherosclerosis
for over a decade. In recent years, LXR modulators have also garnered
interest for potential use in the treatment of inflammation, Alzheimer’s
disease (AD), dermatological conditions, hepatic steatosis, and oncology.
To date, no LXR modulator has successfully progressed beyond phase
I clinical trials. In this Perspective, we summarize published medicinal
chemistry efforts in the context of the available crystallographic
data, druglikeness, and isoform selectivity. In addition, we discuss
the challenges that need to be overcome before an LXR modulator can
reach clinical use.