{"paper_id":"ea5d9660-5b08-4c38-ab6e-b9a0b5286f36","body_text":"Abstract\nEstrogen receptors exist as two subtypes ERα and ERβ, which are characterized by various distributions in\nhuman tissues and diverse transcription regulation. Ligands capable of selective ERβ activation show positive effects in\ntreatment of such diseases as certain cancers, endometriosis, inflammatory diseases, and assist in maintaining\ncardiovascular and nervous system health. Thus far, there are no pharmaceutical drugs available acting on this target. In\norder to provide new treatment for such diseases, a new generation of selective estrogen receptor modulators is required.\nThis remains an unsolved task due to several difficulties. It is known that minor modifications of ER agonists can\ninfluence the selectivity of their binding. The majority of designed ligands acting on ER possess chiral centers thus exist\nas stereoisomers. Unfortunately, not every spatial isomer is individually considered in experimental research. The\nmolecular docking was applied to investigate the structural basis of diverse selectivity and binding affinity of selected\nestrogen receptor β agonists. Docking simulations revealed that terminal aromatic rings positioned in the A- and D-ring\nregions are a factor that determines binding affinity of ERβ agonists. This positioning can be ascribed to the presence of\ntwo terminal hydroxyl groups, a rigid linker, and the introduction of aliphatic substituents. The side substituents of\nunderlined molecular scaffold should adopt inside characterized cavities I and II in order to provide selectivity. The\nbulkiness, attachment to linker and stereochemistry of the substituents affect ERβ selectivity. These molecular features\nshould be considered during search and design of new improved ERβ agonists.\nKeywords: Estrogen receptor beta, selective agonists, structure based drug design, pharmacophore model, docking, molecular recognition.\n61","source_license":"public-domain-us","license_restricted":false}