Inhibition of gsk-3.beta.

A - Human Necessities – 61 – K

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A61K 33/14 (2006.01) A01K 67/027 (2006.01) A61K 31/00 (2006.01) A61K 38/19 (2006.01) A61K 45/00 (2006.01) A61P 29/00 (2006.01) A61P 35/00 (2006.01) C07K 16/24 (2006.01) C12N 5/06 (2006.01)

Patent

CA 2395284

The activity of NF-kB is modulated through the effects of GSK-3 on NK-kB activity. Inhibition or down-regulation of GSK-3 results in decreased NF-kB activity. Inappropriate activation of NF-kB has been linked to inflammation and hyperproliferative disorders. Development of modulatory strategies provide a novel therapeutic tool for the treatment or prevention of various diseases. Methods are also provided for enhanced killing of tumor cells through the sensitization action of GSK-3 inhibition, when administered in conjunction with apoptosis inducing ligands of TNFR1. Transgenic animals defective in GSK- 3 function are also provided.

Selon l'invention, l'activité du facteur nucléaire kB (NF-kB) est modulée via les effets de GSK-3 sur l'activité du NF-kB. L'inhibition ou la régulation négative de GSK-3 mène à une décroissance de l'activité du NF-kB. Une activation inappropriée de NF-kB est liée à des troubles inflammatoires et hyperproliférants. Le développement de stratégies modulantes assure un outil thérapeutique destiné au traitement ou à la prévention de maladies variées. L'invention concerne aussi des procédés permettant une augmentation de l'élimination de cellules tumorales par l'action de sensibilisation de l'inhibition de GSK-3, lorsqu'elle est réalisée avec une administration conjointe de ligands de TNFR1 inducteurs d'apoptose. L'invention concerne encore des animaux transgéniques déficients en fonction GSK-3.

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