Itraconazole-d5 (Synonyms: R51211-d5)

Itraconazole-d₅ is intended for use as an internal standard for the quantification of itraconazole 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

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 neoformansAntimicrob. 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 growthCancer Cell17(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 BAntimicrob. 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 proteinCell Rep.10(4)600-615(2015)