Methods and compositions for restoring conformational...

A - Human Necessities – 61 – K

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A61K 31/5415 (2006.01) A61K 31/473 (2006.01) A61K 31/496 (2006.01) A61K 31/517 (2006.01) A61P 35/00 (2006.01) G01N 33/50 (2006.01)

Patent

CA 2350597

The invention provides pharmaceutical non-peptidic organic compounds capable of interacting with a functionally defective form of a mutant or a wild-type tumor suppressor protein of the p53 family (such as p53, p63 or p73). The interaction allows stabilization or folding of the protein in a functional conformation, thereby restoring all or part of its wild-type normal activity. More particularly said compounds interact with the DNA binding domain of p53 family proteins, are acridine, quinoline, quinazoline or phenothiazine derivatives, and are used in cancer therapy. Also provided are methods for screening such pharmacological compounds.

Cette invention se rapporte au domaine du traitement du cancer et, en particulier, à des composés pharmaceutiques capables d'interagir avec des formes mutantes et non mutantes de protéines régulatoires liées au cancer, de telle sorte que la protéine mutante retrouve la capacité d'interagir correctement avec d'autres molécules, afin de rétablir ou de stabiliser la totalité ou une partie de son activité de type sauvage. Ces protéines régulatoires peuvent être par exemple des membres de la famille des protéines p53, par exemple p53, p63 et p73. Les composés faisant l'objet de cette invention sont utiles pour le traitement du cancer. Des procédés de criblage de tels composés pharmacologiques sont également présentés.

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