Methods and compounds for modulating nuclear receptor...

C - Chemistry – Metallurgy – 12 – Q

Patent

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Details

C12Q 1/00 (2006.01) A61K 38/04 (2006.01) C07B 61/00 (2006.01) C07D 209/82 (2006.01) C07D 209/88 (2006.01) C07D 225/08 (2006.01) C07D 403/06 (2006.01) C07D 403/14 (2006.01) C07K 1/04 (2006.01) C07K 5/00 (2006.01) C07K 7/08 (2006.01) C07K 7/56 (2006.01) G01N 33/53 (2006.01) G01N 33/543 (2006.01) G01N 33/566 (2006.01) G01N 33/567 (2006.01) G01N 33/68 (2006.01)

Patent

CA 2415103

The present invention relates to methods and agonist/antagonist compounds for modulating nuclear receptor coactivator binding. The invention includes a method for identifying residues comprising a coactivator binding site for a nuclear receptor of interest. Also included is a method of identifying agonists and/or antagonists that bind to a coactivator binding site of a nuclear receptor of interest. Agonists and antagonists of coactivator binding to nuclear receptors also are provided. The invention is exemplified by identification and manipulation of the coactivator binding site of the thyroid receptor (TR), and compounds that bind to this sites. The methods can be applied to other nuclear receptors including RAR, RXR, PPAR, VDR, ER, GR, PR, MR, and AR.

Cette invention se rapporte à des procédés et à des composés agonistes/antagonistes servant à moduler la fixation de coactivateurs à des récepteurs nucléaires. Cette invention concerne un procédé servant à identifier des résidus comprenant un site de liaison de coactivateurs pour un récepteur nucléaire examiné. Cette invention concerne également un procédé servant à identifier des agonistes et/ou des antagonistes qui se fixent à un site de fixation de coactivateurs d'un récepteur nucléaire examiné. Des agonistes et des antagonistes de fixation de coactivateurs à des récepteurs nucléaires sont également présentés. Cette invention fournit des exemples d'identification et de manipulation du site de fixation de coactivateurs aux récepteurs thyroïdiens (TR), et des composés qui se fixent à ces sites. Ces procédés peuvent s'appliquer à d'autres récepteurs nucléaires, tels que RAR, RXR, PPAR, VDR, ER, GR, PR, MR et AR.

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