NR4A1

Nuclear Receptor Subfamily 4 Group A Member 1 (NR4A1), alias Nur77, TR3, or NGFI-B, is an orphan nuclear receptor without identified endogenous ligands. As a transcription factor, it binds to Nur77 response elements (NBRE) or direct repeat 5 (DR5) motifs in target gene promoters, regulating cell proliferation, apoptosis, and inflammation. It integrates signals from MAPK/ERK, PI3K/Akt, and NF-κB pathways.
NR4A1 links to diverse diseases: context-dependent tumor suppressor/oncogene in leukemia and breast cancer; modulates inflammation in rheumatoid arthritis; affects metabolic homeostasis in diabetes. Preclinical studies show cytosporone B (agonist) inhibits tumor growth, while antagonists may treat autoimmunity. No FDA-approved NR4A1-targeted drugs exist yet.