Itraconazole-d₅

Itraconazole-d₅ is intended for use as an internal standard for the quantification of itraconazole (Item No. 13288) by GC- or LC-MS. Itraconazole is an antifungal agent and inhibitor of hedgehog signaling (IC₅₀ = 800 nM).^1,2 It binds to 14-α sterol demethylase/CYP51 isoform B (AF51B; K_d = 31 nM for A. fumigatus enzyme expressed in E. coli) and inhibits ergosterol biosynthesis in C. neoformans (IC₅₀ = 6 nM after a 16-hour incubation).^1,3 It inhibits the growth of C. neoformans by 50% when used at a concentration of 3.2 nM. Itraconazole inhibits hedgehog signaling, reducing accumulation of Smoothened induced by sonic hedgehog (Shh) in primary cilia of NIHT-3T3 cells.² It suppresses growth of medulloblastomas in a Ptch^+/-p53^-/- mouse allograft model when administered at a dose of 100 mg/kg twice daily. Itraconazole (1.25-100 µM) also reduces viral titers of several enteroviruses, including human rhinovirus 17, in infected cells, effects that can be reversed by overexpression of OSBP, the gene encoding oxysterol-binding protein (OSBP).⁴

WARNING This product is not for human or veterinary use.

1. Vanden Bossche, H., Marichal, P., Le Jeune, L., et al. Effects of itraconazole on cytochrome P-450-dependent sterol 14α-demethylation and reduction of 3-ketosteroids in Cryptococcus neoformans. Antimicrob. Agents Chemother. 37(10), 2101-2105 (1993).

2. Kim, J., Tang, J.Y., Gong, R., et al. Itraconazole, a commonly used antifungal that inhibits Hedgehog pathway activity and cancer growth. Cancer Cell 17(4), 388-399 (2010).

3. Warrilow, A.G., Melo, N., Martel, C.M., et al. Expression, purification, and characterization of Aspergillus fumigatus sterol 14-a demethylase (CYP51) isoenzymes A and B. Antimicrob. Agents Chemother. 54(10), 4225-4234 (2010).

4. Strating, J.R.P.M., van der Linden, L., Albulescu, L., et al. Itraconazole inhibits enterovirus replication by targeting the oxysterol-binding protein. Cell Rep. 10(4), 600-615 (2015).