product name Itraconazole
Description: Itraconazole is a relatively potent inhibitor of CYP3A4, and used as a triazole antifungal agent. Itraconazole has also recently been explored as an anticancer agent for patients with basal cell carcinoma, non-small cell lung cancer, and prostate cancer. Itraconazole was a substrate for CYP3A and to characterize the metabolites generated. Itraconazole exhibited an unbound Km of 3.9 nM for CYP3A.
References: Drug Metab Dispos. 2004 Oct;32(10):1121-31; Cancer Cell. 2010 Apr 13;17(4):388-99.
705.65
Formula
C35H38Cl2N8O4
CAS No.
84625-61-6
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 7 mg/mL (9.9 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
5% DMSO+70% PEG 300+ddH2O: 9mg/mL
Synonyms
R 51211
other peoduct :
| In Vitro |
In vitro activity: Itraconazole is metabolized into hydroxy-itraconazole (OH-ITZ), a known in vivo metabolite of ITZ, and two new metabolites: keto-itraconazole (keto-ITZ) and N-desalkyl-itraconazole (ND-ITZ). Itraconazole is a substrate for CYP3A in vitro and to characterize the metabolites generated. Itraconazole exhibits an unbound Km of 3.9 nM for CYP3A. Itraconazole metabolites are as potent as or more potent CYP3A4 inhibitors than ITZ itself. Itraconazole appears to act on the essential Hh pathway component Smoothened (SMO) by a mechanism distinct from that of cyclopamine and other known SMO antagonists, and prevents the ciliary accumulation of SMO normally caused by Hh stimulation. Itraconazole is active against 60 clinical isolates of Aspergillus spp. with geometric mean (GM) MICs of 0.25 mg/mL. Itraconazole acts primarily by impairing the synthesis of ergosterol, resulting in a defective fungal cell membrane with altered permeability and function. Itraconazole is effective for a wide variety of mycotic infections and some fungal meningeal infections. Itraconazole has an affinity for mammalian cytochrome P-450 enzymes as well as for fungal P-450-dependent enzyme, and thus has the potential for clinically important interactions (e.g., astemizole, terfenadine, rifampin, oral contraceptives, H2 receptor antagonists, warfarin, cyclosporine). Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | Itraconazole, like other Hh pathway antagonists, can suppress Hh pathway activity and the growth of medulloblastoma in a mouse allograft model; Oral Administration of itraconazole (200 mg) once daily for 4 days increased the area under the midazolam concentration-time curve from 10 to 15 times (p < 0.001) and mean peak concentrations three to four times (p < 0.001) compared with the placebo phase |
| Animal model | |
| Formulation & Dosage | Oral Administration |
| References | Drug Metab Dispos. 2004 Oct;32(10):1121-31; Cancer Cell. 2010 Apr 13;17(4):388-99. |
