Methods and compounds for modulating nuclear receptor activity

G - Physics – 01 – N

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G01N 33/48 (2006.01) G01N 33/68 (2006.01)

Patent

CA 2324060

The present invention relates to methods and agonist/antagonist compounds for modulating nuclear receptor activity, and nuclear receptor ligand binding. The invention includes a method for identifying residues comprising a ligand binding domain for a nuclear receptor of interest. Also included in a method of identifying agonists and/or antagonists that bind to the ligand binding domain of the nuclear receptors, and the estrogen receptor in particular. The invention is exemplified by identification and manipulation of the ligand binding domain of the estrogen receptor and compounds that bind to this site. The methods can be applied to other nuclear receptors including TR, GR and PR.

La présente invention concerne des méthodes et des composés d'agonistes/antagonistes de modulation de l'activité de récepteurs nucléaires, et de liaison aux ligands de récepteurs nucléaires. L'invention concerne une méthode d'identification de résidus comprenant un domaine de liaison aux ligands d'un récepteur nucléaire présentant un certain intérêt. L'invention concerne également une méthode d'identification d'agonistes et/ou d'antagonistes se liant au domaine de liaison aux ligands des récepteurs nucléaires, et du récepteur d'oestrogènes en particulier. L'identification et la manipulation du domaine de liaison aux ligands du récepteur d'oestrogènes et de composés se liant à ce site illustrent la présente invention. Les méthodes selon la présente invention peuvent s'appliquer à d'autres récepteurs nucléaires, y compris TR, GR, et PR.

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