Methods for modulating activity of the fxr nuclear receptor

Details Methods for modulating activity of the fxr nuclear receptor Methods for modulating activity of the fxr nuclear receptor

G - Physics

01

N

G01N 33/566 (2006.01) A61K 31/00 (2006.01) A61K 31/4174 (2006.01) A61K 45/00 (2006.01) A61P 3/06 (2006.01) C12Q 1/02 (2006.01) C12Q 1/68 (2006.01) G01N 33/74 (2006.01)

Patent

CA 2462185

The present invention relates to methods and compositions for modulating genes which are controlled by the FXR nuclear hormone receptor such as Cyp7a, Cyp8b, phospholipid transfer protein, ileal bile acid binding protein, sodium taurocholate cotransporter protein, liver fatty acid binding protein and bile salt export pump. In a preferred embodiment, the method involves modulation of the gene encoding Cyp7a, the enzyme responsible for a major pathway in the elimination of cholesterol. The invention also relates to methods for screening compounds which bind to and activate or inhibit the FXR nuclear hormone receptor and compounds which activate or inhibit the FXR nuclear hormone receptor.

La présente invention concerne des méthodes et des compositions permettant de moduler des gènes qui sont contrôlés par le récepteur nucléaire FXR tel qu'une enzyme Cyp7a, Cyp8b, une protéine de transfert de phospholipides, une protéine de fixation aux acides biliaires iléaux, une protéine cotransporteuse de taurocholate de sodium, une protéine de fixation aux acides gras, une protéine de fixation aux acides gras hépatiques et une pompe de transfert de sels biliaires. Selon un mode de réalisation préféré, ladite méthode consiste à moduler le gène codant l'enzyme Cyp7a, responsable du mécanisme principal dans l'élimination du cholestérol. L'invention concerne également des méthodes de criblage de composés qui se fixent au et activent ou inhibent le récepteur de l'hormone nucléaire FXR et de composés qui activent ou inhibent le récepteur de l'hormone nucléaire FXR.

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