General description

A cell-permeable, orally available triazole-class antifungal agent that, in addition to its known inhibitory activity against fungal cytochrome P450 14-α-demethylase, also acts as an effective Hh signaling inhibitor (IC₅₀ ~0.8 µM against SHHN-induced Gli transcription activity in Shh-Light2 cells) in a Ptch-independent manner (IC₅₀ ~0.9 µM against Ptch promoter-mediated transcription activity in murine Ptch^-/- fibroblasts), presumably by binding smoothened (smo) at a site distinct from that targeted by cyclopamine (Cat. No. 239803) and SAG (Cat. No. 566660), as Itraconazole does not compete with BODIPY-cyclopamine binding, and it alters only the magnitude, but not the EC₅₀, of SAG-induced Gli transcription activity in Shh-Light2 cells. Shown to effectively suppress Hh pathway-dependent growth of both engrafted medulloblastoma and endogenous basal cell carcinoma in mice in vivo (37.5 to 100 mg/kg/12 hr, p.o.) in a reversible manner.

A cell-permeable, orally available triazole-class antifungal agent that, in addition to its known inhibitory activity against fungal cytochrome P450 14-α-demethylase, also acts as an effective Hh signaling inhibitor (IC₅₀ ~ 0.8 µM against SHHN-induced Gli transcription activity in Shh-Light2 cells) in a Ptch-independent manner (IC₅₀ ~ 0.9 µM against Ptch promoter-mediated transcription activity in murine Ptch^-/- fibroblasts), presumably by binding smoothened (smo) at a site distinct from that targeted by cyclopamine (Cat. No. 239803) and SAG (Cat. No. 566660), as Itraconazole does not compete with BODIPY-cyclopamine binding, and it alters only the magnitude, but not the EC₅₀, of SAG-induced Gli transcription activity in Shh-Light2 cells. Shown to effectively suppress Hh pathway-dependent growth of both engrafted medulloblastoma and endogenous basal cell carcinoma in mice in vivo (37.5 to 100 mg/kg/12 hr, p.o.) in a reversible manner.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Other Notes

Kim, J., et al. 2010. Cancer Cell17, 388.

Packaging

250 mg in Glass bottle

Packaged under inert gas

Reconstitution

Following reconstituiton, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Warning

Toxicity: Harmful (C)