C - Chemistry – Metallurgy – 12 – Q
Patent
C - Chemistry, Metallurgy
12
Q
C12Q 1/68 (2006.01) A61K 31/00 (2006.01) A61K 45/00 (2006.01) A61K 49/00 (2006.01) C12Q 1/48 (2006.01) G01N 33/53 (2006.01)
Patent
CA 2251575
Compounds which interfere with the function of the cdc6 protein to form or maintain pre-replication complexes in an animal cell without impairing the cell's ability to activate cyclin dependent kinases that promote S phase and/or M phase for use in cancer therapy due to their ability to kill tumour cells by inhibiting DNA replication. Method for screening for such compounds. There is now considerable evidence that chromosome duplication is triggered by the activation in late G1 of particular cyclin dependent kinases, known as S phase promoting Cdks. It was an object of the present invention to further investigate the mechanisms involved in DNA replication and, utilizing the obtained results, as opposed to conventional chemotherapy, does not damage DNA per se but interferes with DNA replication.
La présente invention concerne des composés entravant la fonction de la protéine cdc6. Ces composés agissent en formant ou en entretenant dans la cellule animale des complexes de pré-réplication sans compromettre l'aptitude de la cellule à activer les kinases cyclino-dépendantes. Favorisant la phase S et/ou la phase M, de telles kinases sont en effet très utiles en cancérothérapie en raison de leur aptitude à tuer les cellules tumorales en bloquant la réplication d'ADN. L'invention concerne également des procédés de sélection systématique de tels composés. On considère maintenant généralement que c'est l'activation, en fin de G1, de kinases cyclino-dépendantes particulières, en l'occurrence des Cdk favorisant la phase S, qui déclenche la duplication chromosomique. Par ailleurs, un approfondissement de la recherche des mécanismes intervenant dans la réplication de l'ADN a permis, dans le cadre de l'invention, de proposer sur la base des résultats obtenus un concept de cancérothérapie qui, contrairement à la chimiothérapie conventionnelle, n'endommage pas l'ADN en soi, mais en entrave la réplication.
Diffley John
Nasmyth Kim
Piatti Simonetta
Boehringer Ingelheim International Gmbh
Fetherstonhaugh & Co.
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