2. Academic Validation
  3. A structure-guided approach to an orthogonal estrogen-receptor-based gene switch activated by ligands suitable for in vivo studies

A structure-guided approach to an orthogonal estrogen-receptor-based gene switch activated by ligands suitable for in vivo studies

  • J Med Chem. 2006 Sep 7;49(18):5404-7. doi: 10.1021/jm060516e.
Olaf Kinzel 1,  Daniela Fattori,  Ester Muraglia,  Paola Gallinari,  Maria Chiara Nardi,  Chantal Paolini,  Giuseppe Roscilli,  Carlo Toniatti,  Odalys Gonzalez Paz,  Ralph Laufer,  Armin Lahm,  Anna Tramontano,  Riccardo Cortese,  Raffaele De Francesco,  Gennaro Ciliberto,  Uwe Koch
Affiliations

Affiliation

  • 1 IRBM (Merck Research Laboratories Rome), Via Pontina km 30,600, 00040 Pomezia, Rome, Italy. olaf_kinzel@merck.com
PMID: 16942012 DOI: 10.1021/jm060516e
Abstract

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.

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