Method for treating diseases associated with abnormal kinase...

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A61K 31/7068 (2006.01) A61K 31/506 (2006.01) A61K 31/706 (2006.01) A61K 45/06 (2006.01) A61P 35/02 (2006.01)

Patent

CA 2474174

Methods are provided for treating diseases associated with abnormal activity of kinases such as chronic myelogenous leukemia. The method comprises: administering a DNA methylation inhibitor to the patient in therapeutically effective amount; and administering a kinase inhibitor such as imatinib mesylate to the patient in therapeutically effective amount, such that the in vivo activity of the kinase is reduced relative to that prior to the treatment. The method can be used to treat cancer associated with abnormal activity of kinases such as phosphatidylinositol 3'-kinase (P13K), protein kinases including serine/threonine kinases such as Raf kinases, protein kinase kinases such as MEK, and tyrosine kinases such as those in the epidermal growth factor receptor family (EGFR), platelet-derived growth factor receptor family (PDGFR), vascular endothelial growth factor receptor (VEGFR) family, nerve growth factor receptor family (NGFR), fibroblast growth factor receptor family (FGFR) insulin receptor family, ephrin receptor family, Met family, Ror family, c-kit family, Src family, Fes family, JAK family, Fak family, Btk family, Syk/ZAP-70 family, and Abl family.

L'invention concerne des procédés permettant de traiter des maladies associées à une activité anormale de kinases, par exemple la leucémie myéloïde chronique. Le procédé consiste à administrer au patient un inhibiteur de méthylation de l'ADN en dose thérapeutiquement efficace; et à administrer au patient un inhibiteur de kinase tel que l'imatinib mésylate en dose thérapeutiquement efficace, l'activité in vivo de la kinase se trouvant alors réduite par rapport à celle antérieure au traitement. Le procédé peut servir dans le traitement de cancers associés à une activité anormale de kinases tels que phosphatidylinositol 3'-kinase (PI3K), protéines kinases comprenant des sérine/thréonine kinases telles que des kinases Raf, kinases de protéines kinase telles que MEK, et tyrosine kinases telles que celles des familles suivantes: récepteur du facteur de croissance épidermique (EGFR), récepteur de facteur de croissance dérivé des plaquettes (PDGFR), récepteur du facteur de croissance endothélial vasculaire (VEGFR), récepteur du facteur de croissance neuronal (NGFR), récepteur d'insuline de la famille du récepteur du facteur de croissance des fibroblastes (FGFR), récepteur d'éphrine, Met, Ror, c-kit, Src, Fes, JAK, Btk, Syk/ZAP-70, et Abl.

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