caa a22 4500 445878452 CHVBK 20180317145534.0 cr unu---uuuuu 170323e20110201xx s 000 0 eng 10.1007/s11030-010-9224-y doi (NATIONALLICENCE)springer-10.1007/s11030-010-9224-y Computer-aided design and synthesis of tetra-aryl-substituted alkenes and their bioevaluation as a selective modulator of estrogen-related receptor γ [Elektronische Daten] [Minseob Koh, Seung Park] This study reports on a translational exercise in computer-aided rational drug design, chemical synthesis, and bioevaluation using a cell-based reporter gene assay, pursued exclusively for the development of specific estrogen-related receptor γ (ERR γ) inverse agonists with selectivity over estrogen receptor α (ER α). We designed and synthesized a 9-membered small-molecule collection, which has, as the key molecular framework, tetra-aryl-substituted alkene derived from 4-hydroxytamoxifen (4-OHT), a known ERR γ inverse agonist and antagonist of ER α. Although we could not achieve a more potent inverse agonist than GSK5182 from our compound collection, we demonstrated a reasonable correlation between the in silico docking simulation and biological data of transcriptional regulation on nuclear receptors. Therefore, we suggest that structural information regarding proteins-of-interest provides a novel insight into the rational design of new therapeutic agents and that the utilization of docking simulation as a preliminary filtering tool might be a useful option for medicinal chemists or chemical biologists. Springer Science+Business Media B.V., 2010 Computational docking nationallicence Estrogen-related receptor γ ( ERR γ ) nationallicence Estrogen receptor α ( ER α ) nationallicence Inverse agonist nationallicence Antagonist nationallicence Tamoxifen analogs nationallicence Koh Minseob Department of Chemistry, Seoul National University, 151-747, Seoul, Korea aut Park Seung Department of Chemistry, Seoul National University, 151-747, Seoul, Korea aut Molecular Diversity Springer Netherlands 15/1(2011-02-01), 69-81 1381-1991 15:1<69 2011 15 11030 https://doi.org/10.1007/s11030-010-9224-y text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11030-010-9224-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Koh Minseob Department of Chemistry, Seoul National University, 151-747, Seoul, Korea aut NATIONALLICENCE 700 1- Park Seung Department of Chemistry, Seoul National University, 151-747, Seoul, Korea aut NATIONALLICENCE 773 0- Molecular Diversity Springer Netherlands 15/1(2011-02-01), 69-81 1381-1991 15:1<69 2011 15 11030 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer