Screening assays for agents that alter inhibitor of...

C - Chemistry – Metallurgy – 12 – Q

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C12Q 1/00 (2006.01) G01N 33/53 (2006.01) G01N 33/68 (2006.01)

Patent

CA 2289972

The present invention relates to an action between an inhibitor of apoptosis (IAP) protein and members of the caspase family of cell death proteases wherein the IAP regulates the activity of the caspases. The invention provides screening assays for identifying agents that alter the specific association of an IAP and a caspase. In addition, the invention provides methods for identifying agents that modulate the activity of a caspase in the presence of an IAP and that regulate the activation of a pro-caspase by an IAP and further provides methods of reducing the severity of a pathologic condition in an individual by administering to the individual an agent that alters the caspase inhibitory activity of an IAP. In addition, the invention provides methods of modulating the ability of a population of cells to survive ex vivo by contacting the cells with an agent that alters the caspase inhibitory activity of an IAP in the cells.

Cette invention a trait à une interaction entre une protéine inhibitrice de l'apoptose (IAP) et des membres de la famille caspase appartenant à la famille des protéases de la mort cellulaire, l'IAP régulant l'activité des caspases. L'invention porte sur des techniques de criblage aux fins de l'identification d'agents modifiant l'association spécifique d'une IAP et d'une caspase. Elle concerne, de surcroît, d'une part, des méthodes d'identification d'agents modulant l'activité d'une caspase en présence d'une IAP et régulant l'activation d'une pro-caspase et, d'autre part, des méthodes visant à atténuer la gravité d'un état pathologique en administrant au patient souffrant de cet état pathologique un agent qui modifie l'activité de l'IAP, en l'occurrence, son activité inhibitrice à l'encontre de la caspase. Cette invention porte, en outre, sur des techniques permettant de moduler les capacités d'une population cellulaire à survivre ex vivo en mettant en contact ces cellules avec un agent modifiant l'activité inhibitrice de l'IAP à l'encontre de la caspase dans lesdites cellules.

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