ERRβ Inhibitors

The chemical class of ERRβ Inhibitors comprises a diverse group of compounds that indirectly modulate the activity of Estrogen-Related Receptor Beta (ERRβ), a nuclear receptor involved in various biological processes. Unlike direct inhibitors, these compounds primarily exert their influence through the modulation of signaling pathways and cellular mechanisms intersecting with ERRβ's role. ERRβ is known for its involvement in metabolic regulation, cellular differentiation, and energy homeostasis. The inhibitors identified for ERRβ do not bind to the receptor directly but instead impact it through secondary effects on various cellular pathways and processes. For instance, compounds like Fulvestrant and Mifepristone, known for their antagonistic action on estrogen and glucocorticoid receptors respectively, may influence ERRβ activity due to the interconnected nature of nuclear receptor signaling pathways. This cross-talk between different receptor pathways can indirectly modulate ERRβ's function, particularly in contexts where these receptors share common target genes or regulatory mechanisms.

Furthermore, the class includes compounds that target key metabolic and signaling pathways, such as PPARγ antagonist T0070907, mTOR activator MHY1485, and AMPK inhibitor Compound C. These compounds alter the metabolic landscape of the cell, potentially affecting ERRβ's role in energy balance and metabolic processes. Additionally, inhibitors like EX-527 and activators like Vorinostat, which modulate sirtuins and histone deacetylases, respectively, impact chromatin remodeling and gene expression. Such epigenetic modifications can indirectly influence ERRβ activity by altering the transcriptional regulation of genes within its network. Similarly, compounds targeting pathways like NRF2, PI3K, ERK, and Wnt, represented by ML385, LY294002, BVD-523, and IWR-1, respectively, demonstrate the extensive reach of these inhibitors.