Small molecule inhibition of a pdz-domain interaction

Details Small molecule inhibition of a pdz-domain interaction Small molecule inhibition of a pdz-domain interaction

C - Chemistry, Metallurgy

07

D

C07D 209/10 (2006.01)

Patent

CA 2572469

Novel compounds that have been found effective in inhibiting PDZ domain interactions, and particularly interactions of PDZ domains in MAGIs with the oncogenic (tumor suppressor) protein PTEN and interactions between the PDZ domain in the Dishevelled (Dvl) protein and other proteins such as the Frizzled (Fz) protein, have the general formula (I) or (III) The invention also includes combinatorial libraries, arrays and methods for screening and studying proteins using such compounds. Compounds of the invention have produced apoptosis in certain cell lines that overexpress the Dishevelled protein (Dvl), inhibiting Wnt signaling.

Des composés novateurs, qui ont été trouvés efficaces pour inhiber des interactions dans le domaine des protéines PDZ et en particulier des interactions dans les domaines de protéines PDZ dans des MAGI grâce à la protéine oncogène (de suppression de tumeur) PTEN et des interactions entre le domaine des protéines PDZ dans la protéine en désordre (Dvl) et d'autres protéines telles que la protéine calcinée (Fz), présentent la formule générale (I) ou (III). L'invention inclut également des bibliothèques, des réseaux et des procédés en combinaison pour passer au crible et étudier des protéines utilisant de tels composés. Les composés de l'invention ont produit une apoptose dans certaines lignes de cellule qui sur-expriment la protéine en désordre (Dvl) en inhibant la transmission de signaux Wnt.

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