419825

Hh Signaling Antagonist X, Itraconazole

The Hh Signaling Antagonist X, Itraconazole, also referenced under CAS 84625-61-6, controls the biological activity of Hh pathway. This small molecule/inhibitor is primarily used for Cell Signaling applications.

• Synonym(s): Hh Signaling Antagonist X, Itraconazole, 14LDM Inhibitor, Oriconazole, R51211, Smo Antagonist VII, Sporanox, 14-α-demethylase Inhibitor
• Empirical Formula (Hill Notation): C₃₅H₃₈Cl₂N₈O₄
• CAS Number: 84625-61-6
• Molecular Weight: 705.63
• MDL number: MFCD00870168
• UNSPSC Code: 12352200
• NACRES: NA.77

Properties

• Quality Level: 100
• assay: ≥98% (HPLC)
• form: powder
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze; protect from light
• color: white
• solubility: DMSO: 10 mg/mL
• shipped in: ambient
• storage temp.: 2-8°C
• InChI: 1S/C35H38Cl2N8O4/c1-3-25(2)45-34(46)44(24-40-45)29-7-5-27(6-8-29)41-14-16-42(17-15-41)28-9-11-30(12-10-28)47-19-31-20-48-35(49-31,21-43-23-38-22-39-43)32-13-4-26(36)18-33(32)37/h4-13,18,22-25,31H,3,14-17,19-21H2,1-2H3/t25?,31-,35-/m0/s1
• InChI key: VHVPQPYKVGDNFY-ZPGVKDDISA-N

Description

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.

Packaging

Packaged under inert gas

Warning

Toxicity: Harmful (C)

Reconstitution

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

Other Notes

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

Legal Information

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

Safety Information

• pictograms: GHS07
• signalword: Warning
• hcodes: H302,H315,H319,H335
• pcodes: P261 - P264 - P271 - P301 + P312 - P302 + P352 - P305 + P351 + P338
• Hazard Classifications: Acute Tox. 4 Oral - Eye Irrit. 2 - Skin Irrit. 2 - STOT SE 3
• target_organs: Respiratory system
• Storage Class: 11 - Combustible Solids
• wgk_germany: WGK 3
• flash_point_f: Not applicable
• flash_point_c: Not applicable