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

Nuclear receptors are members of a large family of ligand-inducible transcr iption 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 detai led insight into the intra- and intermolecular mechanisms that constitute t he initial events of receptor activation and signal transduction. Here, a c omprehensive mechanistic view of agonist and antagonist action will be pres ented. Furthermore, the novel class of partial agonists-antagonists will be described and the multiple challenges and novel perspectives for nuclear-r eceptor-based drug design will be discussed.