Itraconazole |
Catalog No.GC11056
One-Click Copy Product Info
|
L'itraconazole (R51211) est un agent antifongique triazolé et un antagoniste puissant et actif par voie orale de la voie de signalisation Hedgehog (Hh) avec une IC50 d'environ 800 nM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 84625-61-6
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
Itraconazole is an orally active antifungal drug that can strongly inhibit the Hedgehog (Hh) signaling pathway, with an IC50 value is 800nM [1]. Itraconazole inhibits the NaV channel in the heart (IC50=4.2μM) and regulates the contractility of the left ventricle of the heart [2]. Itraconazole inhibits ergosterol synthesis by interacting with the substrate binding site of the fungal 14α-demethylase, increasing cell membrane permeability and disrupting cell membrane integrity[3]. Itraconazole has been widely used to inhibit the growth of various tumor cells and promote autophagy in cancer cells[4].
In vitro, Itraconazole treatment for 36 hours significantly inhibited the proliferation of human umbilical vein endothelial cells (HUVECs), with an IC50 value of 0.16µM[5]. Treatment of MCF-7 cells with 20µg/ml Itraconazole for 24 hours significantly induced cell death, accompanied by changes in mitochondrial membrane potential[6]. Treatment of SW-480 cells with 5µM Itraconazole for 48 hours significantly promoted cell apoptosis, induced G1 phase cell cycle arrest and significantly accumulated autophagosomes[7].
In vivo, Itraconazole treatment via intravenous administration at a dose of 20mg/kg/day for 4 days significantly reduced the fungal load in the lung tissues of mice with invasive pulmonary aspergillosis (IPA) and improved the survival rate of the mice[8]. Oral administration of 75mg/kg of Itraconazole twice daily for 2 weeks significantly inhibited tumor growth in a xenograft mouse model of MKN45 cells[9].
References:
[1] Kim J, Tang J Y, Gong R, et al. Itraconazole, a commonly used antifungal that inhibits Hedgehog pathway activity and cancer growth[J]. Cancer cell, 2010, 17(4): 388-399.
[2] Qu Y, Fang M, Gao B X, et al. Itraconazole decreases left ventricular contractility in isolated rabbit heart: mechanism of action[J]. Toxicology and applied pharmacology, 2013, 268(2): 113-122.
[3] De Beule K, Van Gestel J. Pharmacology of itraconazole[J]. Drugs, 2001, 61(Suppl 1): 27-37.
[4] Wei X, Liu W, Wang J Q, et al. “Hedgehog pathway”: a potential target of itraconazole in the treatment of cancer[J]. Journal of cancer research and clinical oncology, 2020, 146(2): 297-304.
[5] Chong C R, Xu J, Lu J, et al. Inhibition of angiogenesis by the antifungal drug itraconazole[J]. ACS chemical biology, 2007, 2(4): 263-270.
[6] Wang X, Wei S, Zhao Y, et al. Anti-proliferation of breast cancer cells with itraconazole: Hedgehog pathway inhibition induces apoptosis and autophagic cell death[J]. Cancer letters, 2017, 385: 128-136.
[7] Deng H, Huang L, Liao Z, et al. Itraconazole inhibits the Hedgehog signaling pathway thereby inducing autophagy-mediated apoptosis of colon cancer cells[J]. Cell Death & Disease, 2020, 11(7): 539.
[8] Tansho S, Abe S, Ono Y, et al. Efficacy of intravenous itraconazole against invasive pulmonary aspergillosis in neutropenic mice[J]. Journal of infection and chemotherapy, 2006, 12(6): 355-362.
[9] Hu Q, Hou Y C, Huang J, et al. Itraconazole induces apoptosis and cell cycle arrest via inhibiting Hedgehog signaling in gastric cancer cells[J]. Journal of Experimental & Clinical Cancer Research, 2017, 36(1): 50.
| Cell experiment [1]: | |
Cell lines | SW-480 cells |
Preparation Method | SW-480 cells were cultured in RPMI 1640 medium supplemented with 10% fetal bovine serum, 100U/ml penicillin, and 100μg/ml streptomycin at 37°C with 5% CO2 and 95% saturated atmospheric humidity. Cells were seeded into 96-well microplates at a density of 5×103 cells/ml for 24h. Various concentrations of Itraconazole (0, 2.5, 5, 10, 20, 40, 60, 80, and 100µM) were added to each well. At the end of the incubation period (48h at 37°C), cell viability was analyzed. |
Reaction Conditions | 0, 2.5, 5, 10, 20, 40, 60, 80, and 100µM; 48h |
Applications | Itraconazole treatment significantly induced cell death of SW-480 cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | BALB/c mice |
Preparation Method | BALB/c mice (6 weeks old) were maintained under a 12h light and 12h dark cycle at a temperature of 25°C and humidity of 50%±10%, free with water and diet. 5×106 MKN45 cells were suspended in 100ml of PBS and injected subcutaneously into the right flank of male nude mice. When tumors reached a size measuring 40 to 70mm3, calculated as V = L × W2/2(V = Tumor volume, L = Length, W = Width), mice were treated with hydroxypropyl-cyclodextrin (vehicle control), Itraconazole (75mg/kg; twice daily by oral administration). Tumors were measured three times per week for 2 weeks. Then mice were sacrificed, and the tumor tissues were isolated for analysis. |
Dosage form | 75mg/kg; twice daily for 2 weeks; p.o. |
Applications | Itraconazole treatment inhibited tumor growth in mice with MKN45 xenografts. |
References: | |
| Cas No. | 84625-61-6 | SDF | |
| Chemical Name | 2-butan-2-yl-4-[4-[4-[4-[[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-1,2,4-triazol-3-one | ||
| Canonical SMILES | CCC(C)N1C(=O)N(C=N1)C2=CC=C(C=C2)N3CCN(CC3)C4=CC=C(C=C4)OCC5COC(O5)(CN6C=NC=N6)C7=C(C=C(C=C7)Cl)Cl | ||
| Formula | C35H38Cl2N8O4 | M.Wt | 705.63 |
| Solubility | ≥ 8.83mg/mL in DMSO | Storage | 4°C, protect from light |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.4172 mL | 7.0859 mL | 14.1717 mL |
| 5 mM | 283.4 μL | 1.4172 mL | 2.8343 mL |
| 10 mM | 141.7 μL | 708.6 μL | 1.4172 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 3 reference(s) in Google Scholar.)