Orphan nuclear receptor (ONR)

Orphan nuclear receptors are transcription factors belonging to the nuclear receptor superfamily, characterized by the absence of known endogenous ligands. This group includes several molecular subtypes such as NR4A1 (Nur77), NR4A2 (Nurr1), NR4A3 (NOR-1), and others. Structurally, they possess typical nuclear receptor domains, including a DNA-binding domain, a ligand-binding domain, and activation domains. ONRs play crucial roles in regulating gene expression linked to cellular proliferation, differentiation, metabolism, immune response, and cell death. ONRs are implicated in major diseases such as cancer, cardiovascular conditions, neurodegenerative disorders, and metabolic syndromes. Current therapeutic strategies seek to develop selective modulators, but the lack of definitive endogenous ligands and their complex gene regulatory networks pose challenges for drug development[1][4][6][7][8].

Other names

ONROrphan NROrphan nuclear hormone receptorNR4A1Nur77NR4A2Nurr1NR4A3NOR-1DAX-1NR0B1SHPSHP-1NR0B2Rev-ErbαRev-ErbβCOUP-TFICOUP-TFIIPNRGCNF

Drugs/ligands act as agonists or antagonists, modulating receptor's activity as transcription factors. Some act by recruiting coactivators or corepressors, altering gene transcription. Ligand binding (if any) can induce conformational changes in the receptor, affecting target gene regulation.