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

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G01N 33/50 (2006.01)

Patent

CA 2604922

The present invention relates to the discovery, identification and characterization of nucleotide sequences that encode novel substrate-targeting subunits of ubiquitin ligases. The invention encompasses nucleotides encoding novel substrate-targeting subunits of ubiquitin ligases: FBPl, FBP2, FBP3, FBP4, FBP5, FBP6, FBP7, FBP8, FBP9, FBPlO, FBPI l, FBP12, FBP13, FBP14, FBP15, FBP16, FBP17, FBP18, FBP19, FBP20, FBP21, FBP22, FBP23, FBP24, and FBP25, transgenic mice, knock-out mice, host-cell expression systems and proteins encoded by the nucleotides of the novel substrate-targeting subunits. The present invention relates to screening assays that use novel and known substrate- targeting subunits of ubiquitin ligases to identify potential therapeutic agents such as small molecules, compounds or derivatives and analogues of the novel and known ubiquitin ligases which modulate activity of the novel and known 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 and differentiative disorders.

L'invention concerne la découverte, l'identification et la caractérisation de séquences nucléotidiques codant pour de nouvelles sous-unités d'ubiquitine ligases ciblant un substrat. L'invention concerne des nucléotides codant pour de nouvelles sous-unités d'ubiquitine ligases ciblant un substrat: FBPl, 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 ainsi que des protéines codées par les nucléotides des nouvelles sous-unités ciblant un substrat. Par ailleurs, l'invention concerne des techniques de criblage utilisant les sous-unités ciblant un substrat nouvelles et connues pour identifier des agents thérapeutiques potentiels tels que de petites molécules, des composés ou dérivés et des analogues des ubiquitine ligases nouvelles et connues qui modulent l'activité de ces dernières, en vue de traiter des troubles de prolifération et de différenciation tels que le cancer, les infections opportunistes majeures, les troubles immunitaires, certaines maladies cardio-vasculaires et les maladies inflammatoires. Par ailleurs, l'invention concerne des protocoles thérapeutiques et des compositions pharmaceutiques conçus pour cibler les ubiquitine ligases et leurs substrats, en vue du traitement de troubles de prolifération et de différenciation.

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