In Vitro screening for ligands of the estrogen receptor

US7166438B2 · kind B2 · utility

Assignee

• SCHERING CORPORATION · US

Inventors

• Vladimir Patchev · Jena, DE
• Youriy Mitev · Jena, DE
• Siegmund Wolf · Bad Klosterlausnitz, DE
• Gernot Langer · Falkensee, DE

Key dates

• Filing date: Nov 20, 2001
• Grant date: Jan 23, 2007
• Expiry date: Nov 20, 2023

Classification

• Technology area (CPC G): Physics
• CPC primary: G01N2500/20
• WIPO field: Measurement
• WIPO sector: Instruments

Abstract

A method for in vitro screening a group of test substances for a ligand using two assay systems, i.e. a cellular or tissue assay system and an enzymatic assay system, is described. First, those test substances are selected which have transcriptional ER-mediated activity measured by an ER-driven reporter gene in the cellular or tissue assay system with an EC50(ER)(half-maximally effective ligand concentration) lower than or equal to 10 nmol/l. Then in an enzymatic assay system the selected test substances having the required transcriptional ER-mediated activity are tested by measuring a physical-chemical interaction (recruitment) of SRC-1 and the ER in the presence of the test substances. The selected ligand activates the ER and induces interaction with the co-present SRC-1 with an E50(ER+SRC) higher than or equal to 100 nmol/l. The ligands found by the inventive screening method are useful for treatment and prevention of neuro-degeneration in the cerebral cortex, especially of age-related cognitive disorders, affective disorders, Alzheimer's diseases and cerebral ischemia/stroke.