Smoothened antagonism for the treatment of hedgehog...

A - Human Necessities – 61 – K

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Details

A61K 31/167 (2006.01) A61K 31/366 (2006.01) A61K 31/4184 (2006.01) A61K 31/4402 (2006.01) A61K 31/4433 (2006.01) A61K 31/4545 (2006.01) A61K 31/502 (2006.01) A61K 45/06 (2006.01) A61P 35/00 (2006.01)

Patent

CA 2738868

The invention provides methods for modulating, e.g., antagonizing, the activity of the Hedgehog signaling pathway, and for treating Hedgehog related disorders such as cancers (e.g., medulloblastoma). In particular, the invention provides methods for inhibiting aberrant growth states resulting from phenotypes such as Ptch Io ss-of- function, Hedgehog gain-of- function, smoothened gain-of- function or GE gain-of-function by administering to a mammal combinations of Smoothened inhibitors (e.g., a compound of Formula I, Formula II, or Formula III, or any of the compounds listed herein or incorporated by reference) and cholesterol biosynthesis pathway inhibitors (e.g., statins), GIi inhibitors, and/or Phosphatidylinositol 3-kinase (P13K) inhibitors.

La présente invention concerne des procédés qui permettent de moduler, par exemple, d'exercer un effet antagoniste sur l'activité de la voie de signalisation Hedgehog, et de traiter des troubles liées à la voie de signalisation Hedgehog tels que des cancers (par exemple, le médulloblastome). En particulier, l'invention concerne des procédés permettant d'inhiber des états de croissance aberrante résultant de phénotypes tels que la perte de fonction Ptch, le gain de fonction Hedgehog, le gain de fonction Smoothened ou le gain de fonction GIi par administration à un mammifère de combinaisons d'inhibiteurs Smoothened (par exemple, un composé de formule I, de formule II, ou de formule III, ou un quelconque des composés se trouvant dans la liste de référence incluse dans la description) et des inhibiteurs de la voie de signalisation de la biosynthèse du cholestérol (par exemple, des statines), des inhibiteurs GIi, et/ou des inhibiteurs de la Phosphatidylinositol 3-kinase (P13K).

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