The core structure of SERMs simulates the 17β-estradiol template. They have two aromatic rings separated by 1-3 atoms (often a stilbene-type of arrangement). Between the two phenyls of the core, SERMs typically have a 4-substituted phenyl group that, when bound to ER, projects from a position of an estratriene nucleus so that helix 12 moves from the receptor opening and blocks the space where coactivator proteins would normally bind and cause ER agonist activity. There has been a lot of variations in the core portion of SERMs while there has been less flexibility with what is tolerated in the side chain. SERMs can be classified by their core structure.