Materials and methods relating to inhibiting the interaction...

A - Human Necessities – 61 – K

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A61K 38/17 (2006.01) C07K 16/18 (2006.01) C12N 5/10 (2006.01) G01N 33/50 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2287344

Mdm2 binds to p53 in cells in which mdm2 is not overexpressed, i.e. in cells in which mdm2 is expressed at normal or low levels, and that in these cells, this interaction targets the p53 for degradation. This finding means that inhibiting mdm2 production and/or inhibiting the binding of mdm2 to p53 allows levels of p53 to increase by reducing the clearance of p53 by mdm2, and can be used to activate p53 function in cells other than those in which mdm2 is overexpressed. This allows the use of an agent having the property of disrupting the binding of p53 and mdm2 or inhibiting the production of mdm2 in a population of cells, in the preparation of a medicament for activating p53, wherein the population of cells do not overexpress mdm2. Such medicaments are useful in the treatment of conditions such as cancer, viral infections or conditions in which p53 or mdm2 is not functional.

Mdm2 se lie à p53 dans des cellules dans lesquelles mdm2 n'est pas surexprimé, c'est-à-dire dans des cellules dans lesquelles mdm2 est exprimé à des niveaux normaux ou faibles et dans ces cellules l'interaction cible p53 pour obtenir une dégradation. Cette découverte signifie que l'inhibition de la production de mdm2 et/ou l'inhibition de la liaison de mdm2 à p53 permet l'augmentation des niveaux de p53 par réduction de la clairance de p53 pour mdm2, et qu'on peut les utiliser pour activer la fonction de p53 dans des cellules autres que celles dans lesquelles mdm2 est surexprimé. Ceci permet d'utiliser un agent capable d'interrompre la liaison de p53 et mdm2 ou d'inhiber la production de mdm2 dans une population de cellules, dans la préparation d'un médicament destiné à activer p53, ladite population de cellules ne surexprimant pas mdm2. On utilise ces médicaments dans le traitement de pathologies telles que le cancer, les infections virales ou les pathologies dans lesquelles p53 ou mdm2 n'est pas fonctionnel.

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