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Discovery of Novel Quinoline-Based Estrogen Receptor Ligands Using Peptide Interaction Profiling

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journal contribution
posted on 24.03.2005, 00:00 by William J. Hoekstra, Hari S. Patel, Xi Liang, Jean-Baptiste E. Blanc, Dennis O. Heyer, Timothy M. Willson, Marie A. Iannone, Sue H. Kadwell, Lisa A. Miller, Kenneth H. Pearce, Catherine A. Simmons, Jean Shearin
Traditional approaches to discovery of selective estrogen receptor modulators (SERMs) have relied on ER binding and cell-based estrogen response element-driven assays to identify compounds that are osteoprotective but nonproliferative in breast and uterine tissues. To discover new classes of potential SERMs, we have employed a cell-free microsphere-based binding assay to rapidly characterize ERα interactions with conformation-sensing cofactor or phage display peptides. Peptide profiles of constrained triarenes were compared to known proliferative and nonproliferative ER ligands to discover potent quinoline-based ligands with minimal Ishikawa cell stimulation.