Estrogen-related receptor alpha (ERRα) (ERRα)

Estrogen-related receptor alpha (ERRα), also known as Estrogen-related receptor 1, is a member of the orphan nuclear receptor superfamily that acts as a ligand-independent transcription factor [1, 2]. It plays a pivotal role in the regulation of cellular energy metabolism, specifically by controlling the expression of genes involved in mitochondrial biogenesis, oxidative phosphorylation, and fatty acid oxidation [1, 4]. ERRα is frequently overexpressed in high-energy-demanding cancers, such as breast, prostate, and colorectal cancers, where it facilitates metabolic reprogramming to support rapid tumor growth and is often associated with poor clinical prognosis [5]. While it shares significant structural homology with the classical estrogen receptors (ERα and ERβ), ERRα does not bind natural estrogens; instead, its activity is primarily regulated by co-activators like PGC-1α [1, 4]. Therapeutic strategies targeting ERRα include the development of inverse agonists, such as XCT790, which aim to disrupt its interaction with co-activators and inhibit its transcriptional activity in oncology and metabolic disease contexts [3, 5]. Sources: [1] UniProt P11474; [2] NCBI Gene 2101; [3] PMID 15533861; [4] PMID 18664618; [5] PMID 21903714.

Other names

ERR1ERRalphaESRRANR3B1Estrogen-related receptor 1Estrogen receptor-like 1

Inverse agonism to inhibit constitutive transcriptional activity or agonism to enhance metabolic gene expression.