Inhibitors for the Vitamin D Receptor-Coregulator Interaction.

摘要: The vitamin D receptor (VDR) belongs to the superfamily of nuclear receptors and is activated by endogenous ligand 1,25-dihydroxyvitamin D3. genomic effects mediated VDR consist activation repression gene transcription, which includes formation multiprotein complexes with coregulator proteins. Coregulators bind many can be categorized according their role as coactivators (gene activation) or corepressors repression). Herein, different approaches develop compounds that modulate interaction between coregulators are summarized. This peptides were identified creating phage display libraries. Subsequent modification these including introduction a tether nonhydrolyzable bonds resulted in first direct VDR-coregulator inhibitors. Later, small molecules inhibit inhibitors using rational drug design high-throughput screening. Early on, allosteric inhibition interactions was achieved antagonists change conformation coregulators. A detailed discussion dual agonist/antagonist given well summary biological cell-based assays vivo studies.