Methods to identify compounds useful for the treatment of...

C - Chemistry – Metallurgy – 12 – Q

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C12Q 1/00 (2006.01) C12N 9/00 (2006.01) G01N 33/53 (2006.01)

Patent

CA 2433795

The present invention relates to the discovery, identification and characterization of nucleotides that encode novel substrate-targeting subunits of ubiquitin ligases. The invention encompasses nucleotides encoding novel substrate-targeting subunits of ubiquitin ligases: FBP1, FBP2, FBP3, FBP4, FBP5, FBP6, FBP7, FBP8, FBP9, FBP10, FBP11,FBP12,FBP13,FBP14,FBP15,FBP16,FBP17,FBP18,FFBP19,FBP20,FBP21,FBP22,FBP23, FBP24, and FBP25, transgenic mice, knock-out mice, host cell expression systems and proteins encoded by the nucleotides of the present invention. The present invention relates to screening assays that use the novel substrate- targeting subunits to identify potential therapeutic agents such as small molecules, compounds or derivatives and analogues of the novel ubiquitin ligases which modulates activity of the novel ubiquitin ligases for the treatment of proliferative and differentiative disorders, such as cancer, major opportunistic infections, immune disorders, certain cardiovascular diseases, and inflammatory disorders. The invention further encompasses therapeutic protocols and pharmaceutical compositions designed to target ubiquitin ligases and their substrates for the treatment of proliferative disorders.

L'invention concerne la découverte, l'identification et la caractérisation de nucléotides qui codent pour de nouvelles sous-unités à ciblage de substrat de ligases d'ubiquitine. L'invention concerne notamment des nucléotides codant pour de nouvelles sous-unités à ciblage de substrat de ligases d'ubiquitine : FBP1, FBP2, FBP3, FBP4, FBP5, FBP6, FBP7, FBP8, FBP9, FBP10, FBP11, FBP12, FBP13, FBP14, FBP15, FBP16, FBP17, FBP18, FBP19, FBP20, FBP21, FBP22, FBP23, FBP24, et FBP25, des souris transgéniques, des souris knock-out, des systèmes d'expression de cellules hôtes et des protéines codées par les nucléotides de la présente invention. L'invention concerne également des essais de criblage qui utilisent les nouvelles sous-unités à ciblage de substrat pour identifier des agents thérapeutiques potentiels, tels que des petites molécules, des composés ou des dérivés et des analogues des nouvelles ligases d'ubiquitine qui modulent l'activité de celles-ci dans le traitement de troubles de prolifération et de différenciation, tels que le cancer, les infections opportunes majeures, les troubles immunitaires, certaines maladies cardiovasculaires et les troubles inflammatoires. L'invention concerne par ailleurs des protocoles thérapeutiques et des compositions pharmaceutiques conçues pour cibler des ligases d'ubiquitine et leurs substrats dans le traitement de troubles de prolifération.

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