[Synthetic ligands for nuclear receptors].

Fat-soluble ligands like steroid hormones serve to activate nuclear receptors. Nuclear receptors are ligand-dependent transcription factors to transcriptionally activate sets of target genes, and such ligand-dependent transcription mediates a number of transcriptional coregulators. Since nuclear receptors form a gene superfamily, their protein structures are divided into several functional domains. The C-terminal ligand binding domain is structurally altered upon ligand binding, and switches interaction of co-transcriptional regulators; from co-repressors to co-activators. Likewise, owing to ligand-dependent structure alteration of the entire receptor proteins, the N-terminal domains of receptors become accessible to co-activators. Synthetic agonists/antagonists are potent to induce structural alteration in ligand-type dependent manner, resulting in pharmacological association with transcriptional co-regulators.