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Trends Pharmacol Sci. 2000 Oct;21(10):381-8.

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

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  • 1Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS/INSERM/ULP, BP 163, 67404 Illkirch Cedex, C.U. de Strasbourg, France.


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.

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