Inhibitors of pghs-2transactivator activity

Details Inhibitors of pghs-2transactivator activity Inhibitors of pghs-2transactivator activity

G - Physics

01

N

G01N 33/50 (2006.01) G01N 33/53 (2006.01)

Patent

CA 2609495

Prostaglandin-endoperoxide H synthase (PGHS-2) converts arachidonic acid to prostaglandin H2. PGHS-2 is an inducible gene product undetectable in most normal human tissues, but abundant in cancer cells. The present invention exploits a previously undisclosed transcriptional function of PGHS-2 distinct from its well-established enzymatic role to identify potential therapeutic agents useful in treating cancer. The method comprises a DNA binding assay in which PGHS-2 protein binding to the C/EBP, CRE and NF-.kappa.B regions of the PGHS-2 promoter in the presence and absence of test compounds is evaluated to identify inhibitors of PGHS-2 transactivation activity.

La synthase H d'endopéroxyde de prostaglandine (PGHS-2) convertit l'acide arachidonique en prostaglandine H2. PGHS-2 est un produit génique inductible, non détectable dans la plupart des tissus humains mais qui est abondant dans les cellules cancéreuses. La présente invention utilise une fonction transcriptionnelle non découverte précédemment de PGHS-2 distincte de son rôle enzymatique bien établi pour identifier les agents thérapeutiques potentiels utiles dans le traitement du cancer. Le procédé comprend un dosage de liaison d'ADN dans lequel la protéine PGHS-2 se liant aux régions C/EBP, CRE et NF-?B du promoteur de PGHS-2 en présence ou en absence de composés de test est évaluée pour identifier les inhibiteurs de l'activité de transactivation de PGHS-2.

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