Kinzel Olaf, Fattori Daniela, Muraglia Ester, Gallinari Paola, Nardi Maria Chiara, Paolini Chantal, Roscilli Giuseppe, Toniatti Carlo, Gonzalez Paz Odalys, Laufer Ralph, Lahm Armin, Tramontano Anna, Cortese Riccardo, De Francesco Raffaele, Ciliberto Gennaro, Koch Uwe
IRBM (Merck Research Laboratories Rome), Via Pontina km 30,600, 00040 Pomezia, Rome, Italy.
J Med Chem. 2006 Sep 7;49(18):5404-7. doi: 10.1021/jm060516e.
A strategy to obtain a fully orthogonal estrogen-receptor-based gene switch responsive to molecules with acceptable pharmacological properties is presented. From a series of tetrahydrofluorenones active on the wild-type estrogen receptor (ER) an inactive analogue is chosen as a new lead compound. Coevolution of receptor mutants and ligands leads to an ER-based gene switch suitable for studies in animal models.
本文提出了一种策略，用于获得一种完全正交的基于雌激素受体的基因开关，该开关对具有可接受药理特性的分子有响应。从一系列对野生型雌激素受体（ER）有活性的四氢芴酮中选择一种无活性类似物作为新的先导化合物。受体突变体和配体的共同进化产生了一种基于ER的基因开关，适用于动物模型研究。
