Nuclear receptor ligand-binding domains: three-dimensional structures, molecular interactions and pharmacological implications

Trends Pharmacol Sci. 2000 Oct;21(10):381-8. doi: 10.1016/s0165-6147(00)01548-0.


Nuclear receptors are members of a large family of ligand-inducible transcription factors that regulate gene programs underlying a plethora of (patho)physiological phenomena. The recent determination of the crystal structures of nuclear receptor ligand-binding domains has provided an extremely detailed insight into the intra- and intermolecular mechanisms that constitute the initial events of receptor activation and signal transduction. Here, a comprehensive mechanistic view of agonist and antagonist action will be presented. Furthermore, the novel class of partial agonists-antagonists will be described and the multiple challenges and novel perspectives for nuclear-receptor-based drug design will be discussed.

Publication types

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

MeSH terms

  • Androgen Antagonists / pharmacology
  • Animals
  • Binding Sites
  • Estrogen Antagonists / pharmacology
  • Glucocorticoids / pharmacology
  • Humans
  • Ligands
  • Receptors, Cytoplasmic and Nuclear / agonists
  • Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors
  • Receptors, Cytoplasmic and Nuclear / chemistry*


  • Androgen Antagonists
  • Estrogen Antagonists
  • Glucocorticoids
  • Ligands
  • Receptors, Cytoplasmic and Nuclear