Comparative Evaluation and Profiling of Chemical Tools for the Nuclear Hormone Receptor Family 2

Nuclear receptors regulate transcription in response to ligand signals and enable the pharmacological control of gene expression. However, many nuclear receptors are still poorly explored and are not accessible to ligand-based target identification studies. In particular, most members of the NR2 family are among the least studied proteins of the class, and apart from the retinoid X receptors (RXR), validated NR2 ligands are very rare. Here, we gathered the NR2 modulators reported in the literature for comparative profiling in uniform test systems. Most candidate compounds displayed insufficient on-target activity or selectivity to be used as chemical tools for NR2 receptors, underscoring the urgent need for further NR2 ligand development. Nevertheless, a small NR2 modulator set could be assembled for application in a chemogenomic fashion.