A new class of estrogen receptor beta-selective activators

摘要

Estrogen action is mediated by binding to two specific estrogen receptors (ERs), ERα and ERβ. The discovery of ERβ in 1996 changed our understanding of estrogen action and sparked intense research efforts to discover its role in normal physiology and its potential as a drug target. Several ERβ-selective and clinically active ligands have since been developed. The first compounds described were those that have a high selective binding affinity for ERβ, such as ERB-041. A second class of agents that have been identified bind to ERβ and ERα with similar affinity but selectively activate ER@, such as liquiritigenin, a flavanone. A recent study has identified 3,3′-diindolylmethane (DIM) as a member of a new class of ERβ activator that does not bind to the ligand binding site, but rather selectively activates ERβ possibly through cellular kinase pathways that target the receptor's ligand-independent activation domain. Although more studies are needed, these findings suggest that compounds that modulate of ERβ activation without directly binding to the receptor might prove to be of significant clinical importance in the future.