Assessing Estrogenic Activity of Classical Estrogen Receptor-Binding Compounds

The classical estrogen receptor α (ERα) has been a clinical therapeutic target for decades. ERα-targeted drugs have shown great clinical success, in particular as antagonists for the treatment of ERα-positive breast cancers. However, ERα-targeted agonists have also been clinically useful (e.g., for the treatment of osteoporosis). The breast cancer field is regularly identifying novel ERα-binding compounds with the goal of identifying new potential ERα-targeted therapeutics. To determine whether such newly identified ERα-binding compounds have clinical potential, it is important to characterize the estrogenic activity (i.e., both receptor-mediated agonism and/or antagonism) of these compounds. This chapter focuses on methods that allow determination of whether an ERα-binding compound acts as an agonist or antagonist of the receptor and whether the compound induces degradation of the receptor.