Itraconazole
Autophagy inducer / inhibits glioblastoma growth / Itraconazole inhibits the conversion of lanosterol to ergosterol via inhibition of the 14-α demethylase, a cytochrome P-450 enzyme1. Clinically useful antifungal agent. It inhibits the proliferation of glioblastoma cells in vitro and in vivo by inducing autophagic progression via inhibiting the trafficking of cholesterol from late endosomes and lysosomes to the plasma membrane2. Inhibits the hedgehog pathway by binding to Smoothened (SMO) via a mechanism distinct from that of cyclopamine3. Inhibits angiogenesis via inhibiting the binding of VEGF to VEGFR24.
Biochemicals & reagents
84625-61-6
Oriconazole; R51211
1) Vanden Bossche et al. (1993), Effects of itraconazole on cytochrome P-450-dependent sterol 14 alpha-demethylation and reduction of 3-ketosteroids in Cryptococcus neoformans; Antimicrob. Agents Chemother., 37 2101 2) Liu et al. (2014), Itraconazole suppresses the growth of glioblastoma through induction of autophagy: involvement of abnormal cholesterol trafficking; Autophagy, 10 1241 3) Kim et al. (2010), Itraconazole, a commonly used antifungal that inhibits Hedgehog pathway activity and cancer growth; Cancer Cell, 17 388 4) Nacev et al. (2011), The antifungal drug itraconazole inhibits vascular endothelial growth factor receptor 2 (VEGFR2) glycosylation, trafficking, and signaling in endothelial cells; J. Biol. Chem., 286 44045
-20°C
TARGET: GPCR; Lysosome; Cytochrome/MDR -- PATHWAY: Hedgehog; Autophagy; Intracellular transport; Cholesterol metabolism; Proliferation -- RESEARCH AREA: Angiogenesis; Cell death; Vesicles -- DISEASE AREA: Cancer; Infectious disease