title: Discovery of natural estrogen receptor modulators with structure-based virtual screening.
abstract: Eleven compounds were identified as estrogen receptor modulators from an in-house natural product database (NPD) by structure-based virtual screening for ERα and ERβ. Among them, 3 compounds were confirmed as ER agonists and 8 compounds were confirmed as ER antagonists by yeast two-hybrid (Y2H) assay, with EC50 values ranging from several micromolar to 100 micromolar. In this study, a novel series of cycloartane triterpenoids isolated from Schisandra glaucescens Diels was found to have ER antagonistic effect, the most potent antagonist of which exhibited activity with EC50 value of 2.55 and 4.68 μM for ERα and ERβ, respectively. Moreover, the types of modulation and subtype selectivity were also investigated through molecular docking simulation.
authors.affiliation: Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
authors.forename: Xianwen
authors.initials: X
authors.lastname: Cao
authors.forename: Jing
authors.initials: J
authors.lastname: Jiang
authors.forename: Shoude
authors.initials: S
authors.lastname: Zhang
authors.forename: Lili
authors.initials: L
authors.lastname: Zhu
authors.forename: Juan
authors.initials: J
authors.lastname: Zou
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Diao
authors.forename: Weilie
authors.initials: W
authors.lastname: Xiao
authors.forename: Lei
authors.initials: L
authors.lastname: Shan
authors.forename: Handong
authors.initials: H
authors.lastname: Sun
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhang
authors.forename: Jin
authors.initials: J
authors.lastname: Huang
authors.forename: Honglin
authors.initials: H
authors.lastname: Li
mesh_terms: D016208:Databases, Factual; D004353:Drug Evaluation, Preclinical; D047628:Estrogen Receptor alpha / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D011485:Protein Binding; D032141:Schisandra / Q000737:chemistry; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D014315:Triterpenes; C085352:cycloartane