REV-ERBα and REV-ERBβ (NR1D1/NR1D2)

REV-ERBα and REV-ERBβ are heme-binding nuclear receptor transcription factors encoded by the NR1D1 and NR1D2 genes, respectively, functioning predominantly as ligand-dependent transcriptional repressors by recruiting corepressors such as NCoR and SMRT and driving histone deacetylation. They lack the activation function 2 (AF-2) region critical for transcriptional activation and act as key regulators of the mammalian circadian clock by rhythmically repressing core clock genes such as BMAL1 and CLOCK. These proteins have overlapping, wide expression patterns, most strongly in metabolic and neural tissues, and regulate diverse processes, including glucose and lipid metabolism, mitochondrial biogenesis, and inflammatory signaling. Their modulation is implicated in diseases such as metabolic syndrome, cardiovascular disorders, neurodegeneration, and certain inflammatory pathologies. Agonists targeting the ligand-binding pocket (notably heme and synthetic molecules like SR9009 and STL1267) are being explored for therapeutic use due to their potential to influence circadian and metabolic gene expression

Other names

EAR-1hRevRev-ErbAalphaTHRA1BD73RVREAR-1rHZF2

Agonists: Bind to the ligand-binding domain and enhance recruitment of corepressors (NCoR, SMRT), leading to histone deacetylation and transcriptional repression of target genes, especially those involved in circadian, metabolic, or immune pathways