Discovery of Novel Quinoline-Based Estrogen Receptor Ligands Using Peptide Interaction Profiling
| Autor: | Dennis Heyer, Jean Baptiste E Blanc, Jean Shearin, Lisa A. Miller, Sue H. Kadwell, Timothy M. Willson, William J. Hoekstra, Xi Liang, Hari S. Patel, Marie A. Iannone, Kenneth H. Pearce, Catherine A. Simmons |
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| Rok vydání: | 2004 |
| Předmět: |
Selective Estrogen Receptor Modulators
Phage display medicine.drug_class Estrogen receptor Peptide Ligands Binding Competitive Cell Line Endometrium Peptide Library Drug Discovery medicine Estrogen Receptor beta Humans Receptor Peptide library Cell Proliferation chemistry.chemical_classification Cell-Free System Ligand binding assay Estrogen Receptor alpha Alkaline Phosphatase Microspheres Receptors Estrogen chemistry Biochemistry Selective estrogen receptor modulator Estrogen Enzyme Induction Quinolines Molecular Medicine Female hormones hormone substitutes and hormone antagonists |
| Zdroj: | Journal of Medicinal Chemistry. 48:2243-2247 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm040154f |
| Popis: | 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 ERalpha 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. |
| Databáze: | OpenAIRE |
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