Schering Aktiengesellschaft

Bayer Schering Pharma Ag

Siegmund Wolf

Maik Obendorf

Vladimir Patchev

Gernot Langer

Jens Schroeder

Youriy Mitev

Rene Meyer

In the method of determining hormonal effects of substances, a test substance is contacted with Ewing sarcoma protein (EWS) or a derivative of it and with an androgen receptor (NR) or a derivative of it; and the effect of the test substance on binding of EWS with the androgen receptor or its derivative or on ligand-induced activity of the androgen receptor is determined, preferably in a cellular system. A method for determining interference in the co-modulator mechanism between androgen receptor and EWS, which includes measurement of androgen receptor and EWS concentrations, is described. A method for identification and characterization of substances that influence the activity of a nuclear receptor, especially androgen receptor, using EWS or a derivative of it is disclosed.

Methods for determining hormonal effects of substances using Ewing sarcoma protein and androgen receptor

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 EC(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 Ehigher 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.

In Vitro screening for ligands of the estrogen receptor

The method for testing of substances for hormonal effects, especially for androgenic or anti-androgenic effects, includes exposing cells transfected with two vectors to the substances, wherein one vector contains a DNA, which codes for a nuclear receptor protein, or a fragment thereof, especially a human nuclear receptor protein, or a fragment thereof, and the other vector contains a DNA, which codes for the HSRNAAM co-modulator, or a fragment thereof; and measuring transcription activity, which the nuclear receptor protein, or its fragment, activates or releases in the presence of the HSRNAAM co-modulator, or its fragment, and/or measuring the influence of the substance on the interaction between the nuclear receptor protein, or its fragment, and the HSRNAAM co-modulator, or its fragment, by protein-protein interaction or by protein-protein-DNA interaction. Also a method for determining interference in the co-modulation mechanism between androgen receptor protein and HSRNAAM co-modulator is described.

Method for testing hormonal effects of substances

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Bad Klosterlausnitz, Germany

Siegmund Wolf