Orphan Nuclear Receptor (孤核受体)

Nuclear receptors consist of 48 transcription factors in humans. Of these, 10 are considered orphan nuclear receptors (ONRs) because the natural ligand has not yet been identified, while 26 are former orphans but are now labeled as adopted NRs after the discovery of their respective natural ligands. Although adopted NRs bind endogenous ligands, it remains unclear whether the NR function is ligand-regulated. The remaining 12 NRs employ endocrine hormones as endogenous ligands and are classified as endocrine NRs. Ligand binding to NRs typically induce a conformational change that enable binding of NRs to target DNA motifs across the genome called nuclear receptor response elements (NRREs) and recruitment of co-regulator proteins that modulate transcription of target genes. Because ONRs could potentially be ligand-regulated or druggable, they are attractive therapeutic targets using small molecule compounds. Orphan nuclear receptors provide a unique resource for uncovering novel regulatory systems that impact human health and also provide drug targets for a variety of human diseases. Ligands of nuclear receptors have been used in several important therapeutic areas, such as breast cancers, skin disorders and diabetes^[1][2].