Compositions and methods for identifying substrate...

G - Physics – 01 – N

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G01N 33/573 (2006.01) C12N 9/64 (2006.01)

Patent

CA 2692604

The invention provides assays and methods for determining the substrate specificity of gamma secretase inhibitors and for identifying substrate-selective (and substrate isoform-selective) inhibitors of gamma secretase. The invention provides assays and methods for determining whether a compound inhibits gamma secretase in a site specific or substrate specific manner. The invention provides isolated polypeptide sequences comprising modified gamma secretase substrates, and polynucleotide sequences encoding the polypeptide sequences. The invention also provides compounds that inhibit gamma secretase, pharmaceutical compositions comprising such compounds, and methods of treating Alzheimer's disease using such compounds.

L'invention concerne des essais et des procédés permettant de déterminer la spécificité de substrat des inhibiteurs de la gamma secrétase et permettant d'identifier les inhibiteurs sélectifs de substrats (et sélectifs d'isoformes substrats) de la gamma secrétase. L'invention concerne des essais et des procédés permettant de déterminer si un composé inhibe la gamma secrétase de manière spécifique au site ou spécifique au substrat. L'invention concerne des séquences de polypeptides isolées comprenant des substrats de gamma secrétase modifiés, et des séquences de polynucléotides codant les séquences de polypeptides. L'invention concerne également des composés qui inhibent la gamma secrétase, des compositions pharmaceutiques comprenant ces composés et des procédés permettant de traiter la maladie d'Alzheimer en utilisant ces composés.

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