Smoothened antagonism for the treatment of hedgehog pathway-related disorders

US8778927B2 · kind B2 · utility

Assignee

• Novartis AG · CH

Inventors

• Marion Dorsch · Brookline, US
• John E. Monahan · Walpole, US
• Michael Patrick Morrissey · Watertown, US
• Shifeng Pan · Gilroy, US
• Juliet Williams · London, GB

Key dates

• Filing date: Sep 28, 2009
• Grant date: Jul 15, 2014
• Expiry date: Feb 9, 2030

Classification

• Technology area (CPC Y): Emerging Cross-Sectional Technologies
• CPC primary: Y02A50/30
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

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 loss-of-function, Hedgehog gain-of-function, smoothened gain-of-function or Gli 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), Gli inhibitors, and/or Phosphatidylinositol 3-kinase (PI3K) inhibitors.