Methods for screening compounds that modulate lipid metabolism

C - Chemistry – Metallurgy – 12 – Q

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C12Q 1/68 (2006.01) C12N 9/02 (2006.01)

Patent

CA 2427024

Drug screening assays useful in the discovery of pharmaceutically active compounds for use in the treatment of diseases involving abnormal lipid metabolism including diabetic neuropathy are taught. In particular, the control region of delta-5-desaturase gene is taught as a target for the drug screening methods, which serve to identify nucleotides, proteins, compounds and/or other pharmacological agents, which modulate the activity of desaturase enzymes or regulate the level of expression of the desaturase genes. Cell- based and cell lysate assays are taught for detecting components that interact with the desaturase enzymes and modify fatty acid profiles. In addition, cell- based and cell lysate assays are used to identify functional and regulatory elements controlling expression of the desaturase genes as well as to screen for components that modulate the transcriptional activity of the desaturase genes. Also taught is the gene for rat delta-5-desaturase.

Cette invention se rapporte à des dosages de criblage de médicaments utiles dans la découverte de composés pharmaceutiquement actifs servant au traitement de maladies impliquant un métabolisme anormal des lipides, tel que la neuropathie diabétique. En particulier, la région témoin du gène de delta-5-désaturase est divulguée comme cible pour ces procédés de criblage de médicaments, qui servent à identifier des nucléotides, des protéines, des composés et/ou d'autres agents pharmacologiques modulant l'activité des enzymes désaturases ou régulant le niveau d'expression des gènes de désaturase. Des dosages de lysats de cellules et à base de cellules sont divulgués pour détecter des composants qui interagissent avec les enzymes désaturases et modifient les profils des acides gras. En outre, des dosages de lysats de cellules et à base de cellules sont utilisés pour identifier les éléments fonctionnels et régulateurs commandant l'expression des gènes de désaturase et pour cribler des composants qui modulent l'activité transcriptionnelle des gènes de désaturase. Est également divulgué le gène de la delta-5-désaturase du rat.

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