Traditional approaches to discovery of selective estrogen receptor modulators (SERMs) haverelied on ER binding and cell-based estrogen response element-driven assays to identifycompounds that are osteoprotective but nonproliferative in breast and uterine tissues. Todiscover new classes of potential SERMs, we have employed a cell-free microsphere-basedbinding assay to rapidly characterize ERα interactions with conformation-sensing cofactor orphage display peptides. Peptide profiles of constrained triarenes were compared to knownproliferative and nonproliferative ER ligands to discover potent quinoline-based ligands withminimal Ishikawa cell stimulation.
