Inhibitors of gsk-3 and crystal structures of gsk-3.beta....

C - Chemistry – Metallurgy – 12 – N

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C12N 9/12 (2006.01) A61K 31/5025 (2006.01) A61P 3/10 (2006.01) A61P 25/28 (2006.01) C07D 487/04 (2006.01) C12P 21/02 (2006.01) G01N 23/20 (2006.01) G06F 17/00 (2006.01) G06F 19/00 (2006.01)

Patent

CA 2444882

The present invention relates to inhibitors of GSK-3 and methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors and methods of utilizing those compositions in the treatment and prevention of various disorders, such as diabetes and Alzheimer's disease. In addition, the invention relates to molecules or molecular complexes which comprise binding pockets of GSK-3.beta. or its homologues. The invention relates to a computer comprising a data storage medium encoded with the structure coordinates of such binding pockets. The invention also relates to methods of using the structure coordinates to solve the structure of homologous proteins or protein complexes. The invention relates to methods of using the structure coordinates to screen for and design compounds that bind to GSK-3.beta. protein or homologues thereof. The invention also relates to crystallizable compositions and crystals comprising GSK-3.beta. protein or GSK-3.beta. protein complexes.

La présente invention concerne des inhibiteurs de GSK-3 et des méthodes de production de ces inhibiteurs; des compositions pharmaceutiques renfermant les inhibiteurs et des méthodes d'utilisation de ces compositions dans le traitement et la prévention de diverses maladies, telles que le diabète et la maladie d'Alzheimer; des molécules ou des complexes moléculaires qui comprennent des poches de liaison de GSK-3.beta. ou de ses homologues; un ordinateur comprenant un moyen de stockage de données dans lequel sont codées les coordonnées structurelles de ces poches de liaison; des méthodes d'utilisation des coordonnées structurelles pour dissoudre la structure des protéines homologues ou des complexes protéiques; des méthodes d'utilisation des coordonnées structurelles pour cribler et mettre au point des composés qui se lient à la protéine GSK-3.beta. ou à ses homologues; et des compositions cristallisables et des cristaux comprenant la protéine GSK-3.beta. ou des complexes protéiques GSK-3.beta..

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