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Publication : Itraconazole, a commonly used antifungal that inhibits Hedgehog pathway activity and cancer growth.

First Author  Kim J Year  2010
Journal  Cancer Cell Volume  17
Issue  4 Pages  388-99
PubMed ID  20385363 Mgi Jnum  J:158946
Mgi Id  MGI:4440975 Doi  10.1016/j.ccr.2010.02.027
Citation  Kim J, et al. (2010) Itraconazole, a commonly used antifungal that inhibits Hedgehog pathway activity and cancer growth. Cancer Cell 17(4):388-99
abstractText  In a screen of drugs previously tested in humans we identified itraconazole, a systemic antifungal, as a potent antagonist of the Hedgehog (Hh) signaling pathway that acts by a mechanism distinct from its inhibitory effect on fungal sterol biosynthesis. Systemically administered itraconazole, like other Hh pathway antagonists, can suppress Hh pathway activity and the growth of medulloblastoma in a mouse allograft model and does so at serum levels comparable to those in patients undergoing antifungal therapy. Mechanistically, itraconazole appears to act on the essential Hh pathway component Smoothened (SMO) by a mechanism distinct from that of cyclopamine and other known SMO antagonists, and prevents the ciliary accumulation of SMO normally caused by Hh stimulation.
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