| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
Neticonazole targets fungal lanosterol 14α-demethylase (CYP51), a key enzyme in the ergosterol biosynthesis pathway. By inhibiting CYP51, Neticonazole prevents the conversion of lanosterol to ergosterol, which is an essential component of the fungal cell membrane. This disruption of ergosterol synthesis leads to increased membrane permeability, leakage of cellular contents, and ultimately fungal cell death. The compound's imidazole ring coordinates with the heme iron of CYP51, resulting in potent and selective inhibition.
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| ln Vitro |
Treatment with neticonazole (10 μM; 48 h) decreased the levels of Alix and Rab27a and markedly decreased the levels of nSMase2. Significant p-ERK level inhibition is possible with neticonazole [2]. Exosome release from C4-2B cells is potently and dose-dependently inhibited by neticonazole (0–10 μM) [2]. Additionally, neticonazole has an aqueous solution-dependent, biogenic wound-active exosome [3].
In vitro, Neticonazole has been shown to possess potent antifungal activity against a variety of fungal pathogens, including Candida albicans. The minimum inhibitory concentration (MIC) of Neticonazole against Candida albicans is in the low micromolar range. The compound's long-acting nature allows for sustained antifungal activity. In addition to its antifungal effects, Neticonazole has been reported to have anti-cancer effects, although the mechanism is not fully understood. It may also inhibit exosome secretion. |
| ln Vivo |
Neticonazole (1–100 ng/kg; administered daily for 15 days via lateral gavage; for cosmetic C57BL/6 hair) dramatically enhances xenografts of colorectal cancer (CRC) that are contaminated with bacterial toxin (IDB).
In vivo, Neticonazole has demonstrated efficacy in animal models of cutaneous Candida albicans infections. The compound's potent and long-acting antifungal activity makes it effective in treating fungal infections. However, its clinical use is limited by its potential to induce contact dermatitis. Neticonazole has also been investigated for its anti-cancer effects in vivo, although these studies are preliminary. |
| Enzyme Assay |
In vitro enzyme assays for Neticonazole involve measuring its inhibition of fungal CYP51. The assay is performed using recombinant CYP51 enzyme or microsomal preparations from fungal cells. The enzyme is incubated with the substrate lanosterol and varying concentrations of Neticonazole. The formation of the product, 14α-demethylated lanosterol, is measured by HPLC or GC-MS. The IC₅₀ value is calculated from the concentration-response curve.
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| Cell Assay |
Western Blot Analysis[2]
Cell Types: C4 -2B Cell Tested Concentrations: 10 µM Incubation Duration: 48 hrs (hours) Experimental Results: diminished Alix and Rab27a levels, and Dramatically diminished nSMase2 levels. In vitro cellular experiments for Neticonazole are performed using fungal cell cultures. The antifungal activity is assessed by determining the MIC using the broth microdilution method. Fungal cells are grown in RPMI medium and incubated with serial dilutions of the compound. The MIC is defined as the lowest concentration of the compound that inhibits visible fungal growth after 24-48 hours of incubation. The fungicidal or fungistatic nature of the compound is determined by time-kill assays. |
| Animal Protocol |
Animal/Disease Models: Male C57BL/6 mice (8 weeks old) given ampicillin, neomycin, metronidazole and vancomycin, and injected with SW480 cells[3]
Doses: 1 ng/kg, 10 ng/kg and 100 ng/kg Route of Administration: po (oral gavage); daily; for 15 days Experimental Results:Dramatically improved the survival of IDB mice with CRC xenograft tumors. In vivo animal studies for Neticonazole are conducted using mouse models of cutaneous Candida albicans infection. The compound is applied topically or administered systemically. The efficacy of the treatment is evaluated by measuring the reduction in fungal burden in the skin lesions. The compound's safety and local tolerability are also assessed. The anti-cancer effects of Neticonazole can be studied in xenograft mouse models. |
| ADME/Pharmacokinetics |
The pharmacokinetic properties of Neticonazole have been characterized in preclinical studies. The compound is well absorbed following topical or oral administration. It has a long half-life, consistent with its long-acting antifungal activity. The compound is metabolized in the liver, and its metabolites are excreted via the biliary and renal routes. The pharmacokinetic profile of Neticonazole supports its use in the treatment of fungal infections.
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| Toxicity/Toxicokinetics |
The toxicity profile of Neticonazole is characterized by its potential to induce contact dermatitis. In preclinical studies, the compound has been shown to be well-tolerated at therapeutic doses, with no significant systemic toxicity observed. However, local skin reactions, including irritation and sensitization, have been reported. The compound's safety in humans has been evaluated in clinical trials, and it is considered safe for topical use.
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| References |
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| Additional Infomation |
Neteconazole is an enamine with an ethylene structure, substituted at positions 1, 1, and 2 with o-pentoxyphenyl, 1H-imidazol-1-yl, and methylthioyl, respectively (E-isomer). It is a P450-dependent lanosterol C-14α-demethylation inhibitor (preventing the conversion of lanosterol to ergosterol and inhibiting fungal cell wall synthesis), commonly used in Japan as an antifungal drug in the form of hydrochloride for the treatment of superficial skin infections. It is both an antifungal drug and an EC 1.14.13.70 (sterol 14α-demethylase) inhibitor. Neteconazole is an aromatic ether, methyl sulfide, imidazole compound, enamine, benzene compound, conazole antifungal drug, and imidazole antifungal drug. It is the conjugate base of neteconazole (1+).
Neticonazole is a potent, long-acting imidazole antifungal agent that inhibits fungal CYP51 and disrupts ergosterol biosynthesis. It is used in the treatment of cutaneous Candida albicans infections. The compound also has anti-infection and anti-cancer effects and can induce contact dermatitis. Neticonazole represents a valuable tool for studying fungal infections and their treatment. |
| Molecular Formula |
C17H22N2OS
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| Molecular Weight |
302.43438
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| Exact Mass |
302.145
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| CAS # |
130726-68-0
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| Related CAS # |
Neticonazole hydrochloride;130773-02-3
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| PubChem CID |
5282433
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| Appearance |
White to off-white solid powder
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| Density |
1.06g/cm3
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| Boiling Point |
464ºC at 760mmHg
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| Flash Point |
234.4ºC
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| Vapour Pressure |
8.66E-09mmHg at 25°C
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| Index of Refraction |
1.558
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| LogP |
4.661
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
21
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| Complexity |
322
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCCCCOC1=CC=CC=C1/C(=C\SC)/N2C=CN=C2
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| InChi Key |
VWOIKFDZQQLJBJ-DTQAZKPQSA-N
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| InChi Code |
InChI=1S/C17H22N2OS/c1-3-4-7-12-20-17-9-6-5-8-15(17)16(13-21-2)19-11-10-18-14-19/h5-6,8-11,13-14H,3-4,7,12H2,1-2H3/b16-13+
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| Chemical Name |
1-[(E)-2-methylsulfanyl-1-(2-pentoxyphenyl)ethenyl]imidazole
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~250 mg/mL (~826.64 mM)
1M HCl : 100 mg/mL (~330.66 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.25 mg/mL (20.67 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 6.25 mg/mL (20.67 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 mg/mL clear DMSO stock solution to 900 μL corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.3066 mL | 16.5328 mL | 33.0655 mL | |
| 5 mM | 0.6613 mL | 3.3066 mL | 6.6131 mL | |
| 10 mM | 0.3307 mL | 1.6533 mL | 3.3066 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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