The Flip Side: Identifying Small Molecule Regulators of Nuclear Receptors Review Article

Members of the nuclear hormone receptor superfamily function as ligand-activated transcription factors to regulate genetic networks controlling cell growth and differentiation, inflammatory responses, and metabolism. The ability to modulate nuclear receptor-dependent gene expression with small molecules has made the superfamily a favored target for drug discovery. Not surprisingly, small molecules that regulate receptor activity are currently used to treat a number of human disorders. Over the last 10 years, the availability of a common platform of functional assays suitable for any nuclear receptor has facilitated the identification of endogenous and synthetic ligands that have been used as tools to uncover previously unanticipated endocrine signaling pathways. Recent progress in understanding the molecular basis for ligand-dependent gene regulation suggests that a new era of “designer” ligands with tissue- and/or gene-selective activity will quickly be upon us.