Method for inhibiting the proliferation of hepatic stellate...

A - Human Necessities – 61 – K

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A61K 31/565 (2006.01) A61K 31/4174 (2006.01) A61K 31/444 (2006.01) A61K 31/57 (2006.01) A61P 1/16 (2006.01) G01N 33/50 (2006.01) G01N 33/74 (2006.01)

Patent

CA 2461357

Provided are methods of inhibiting proliferation and/or trans-differentiation of hepatic stellate cells, which method comprises the step of contacting hepatic stellate cells with a ligand of the low affinity glucocorticoid binding site (LAGS), which may be the rat p28 receptor or the human hpr6.6 receptor. The invention also provides ligands for use in such methods (e.g. pregnenolone 16-alpha carbonitrile) and methods for screening for the same (e.g. based on competition or displacement assays using LAGS ligands such as dexamethasone). Such ligands may be used in the treatment of liver disorders.

L'invention concerne des procédés d'inhibition de la prolifération et/ou transdifférenciation de cellules hépatiques de Kupffer, consistant à mettre en contact les cellules hépatiques de Kupffer avec un ligand du site de liaison aux glucocorticoïdes à faible affinité (LAGS), qui peut être le récepteur p28 murin ou le récepteur hpr6,6 humain. Par ailleurs, l'invention concerne des ligands utilisés dans ces procédés (par exemple, 16-alpha carbonitrile de prégnenolone) ainsi que des procédés de criblage (basés par exemple sur des dosages par compétition ou déplacement faisant intervenir les ligands LAGS, notamment la dexaméthasone). On peut utiliser ces ligands pour traiter les troubles hépatiques.

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