Liver X receptor biology and pharmacology: new pathways, challenges and opportunities

Trends Pharmacol Sci. 2012 Jul;33(7):394-404. doi: 10.1016/ Epub 2012 Apr 27.


Nuclear receptors (NRs) are master regulators of transcriptional programs that integrate the homeostatic control of almost all biological processes. Their direct mode of ligand regulation and genome interaction is at the core of modern pharmacology. The two liver X receptors LXRα and LXRβ are among the emerging newer drug targets within the NR family. LXRs are best known as nuclear oxysterol receptors and physiological regulators of lipid and cholesterol metabolism that also act in an anti-inflammatory way. Because LXRs control diverse pathways in development, reproduction, metabolism, immunity and inflammation, they have potential as therapeutic targets for diseases as diverse as lipid disorders, atherosclerosis, chronic inflammation, autoimmunity, cancer and neurodegenerative diseases. Recent insights into LXR signaling suggest future targeting strategies aiming at increasing LXR subtype and pathway selectivity. This review discusses the current status of our understanding of LXR biology and pharmacology, with an emphasis on the molecular aspects of LXR signaling that constitute the potential of LXRs as drug targets.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cholesterol / analogs & derivatives
  • Cholesterol / chemistry
  • Cholesterol / pharmacology
  • Drug Design
  • Homeostasis / physiology
  • Humans
  • Liver X Receptors
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Molecular Targeted Therapy
  • Orphan Nuclear Receptors / agonists*
  • Orphan Nuclear Receptors / chemistry
  • Orphan Nuclear Receptors / physiology*
  • RNA, Messenger / biosynthesis
  • Transcription Factors / metabolism


  • Liver X Receptors
  • NR1H3 protein, human
  • Nr1h3 protein, mouse
  • Orphan Nuclear Receptors
  • RNA, Messenger
  • Transcription Factors
  • Cholesterol