| Size | Price | Stock | Qty |
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| Targets |
Dapaconazole targets the fungal cytochrome P450 enzyme lanosterol 14α-demethylase (CYP51). This enzyme is essential for the synthesis of ergosterol, a critical component of the fungal cell membrane. Inhibition of CYP51 disrupts ergosterol production, leading to membrane permeability changes and fungal cell death. The compound also shows modest activity against human CYP26 (IC50 ~1.4 µM), but is highly selective for fungal CYP51 over human CYP enzymes.
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| ln Vitro |
Dapaconazole has an IC50 of 1.4 ± 0.3 μM, which means that it inhibits the activity of cytochrome P450 that demethylates sterol 14α [1].
In vitro, Dapaconazole demonstrates potent activity against a broad spectrum of fungi, including dermatophytes (Trichophyton, Microsporum), yeasts (Candida albicans, Cryptococcus), and molds (Aspergillus fumigatus). Minimum inhibitory concentrations (MICs) are typically in the range of 0.03-1 µg/mL. The compound's structure provides enhanced binding affinity and metabolic stability compared to earlier azoles, with lower potential for drug-drug interactions. |
| ln Vivo |
Dapatconazole (20 mg/kg; oral) has a 97.3% bioavailability [1].
In vivo, Dapaconazole tosylate has been evaluated in Phase II clinical trials for pityriasis versicolor. In a randomized, double-blind trial, a 20 mg/day dose administered for 28 consecutive days was found to be non-inferior to ketoconazole 200 mg/day, with good clinical and mycological cure rates. The compound was well tolerated with no serious adverse events reported. |
| Enzyme Assay |
In cell-free enzymatic assays, Dapaconazole's activity is measured by inhibition of fungal CYP51. Microsomal fractions from Candida albicans are incubated with [14C]-lanosterol and NADPH in the presence of varying compound concentrations. The conversion to 14-demethylated products is quantified by TLC or HPLC. The IC50 is calculated from the inhibition of ergosterol synthesis. Alternatively, a fluorescence-based assay using recombinant CYP51 can be employed.
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| Cell Assay |
Cell-based antifungal susceptibility testing follows CLSI (M27-A3) broth microdilution guidelines. Fungal inocula (0.5-2.5 × 10^3 CFU/mL) are incubated in RPMI 1640 medium with serial two-fold dilutions of Dapaconazole in 96-well plates. After 24-48 hours at 35°C, the MIC is read as the lowest concentration that inhibits visible growth. Reference strains (e.g., C. albicans ATCC 90028) are used for quality control.
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| Animal Protocol |
Animal/Disease Models: Male beagle [1]
Doses: 20 mg/kg (pharmacokinetic/PK/PK analysis) Route of Administration: Po Experimental Results: Bioavailability was shown to be 97.3%. In vivo efficacy models include guinea pig or mouse models of dermatophytosis or candidiasis. For example, guinea pigs are infected on shaved back skin with Trichophyton mentagrophytes, then treated topically with Dapaconazole cream or gel daily for 7 days. Lesions are scored clinically, and skin biopsies are taken for fungal culture and histopathology. Oral models are also used for systemic infections. |
| ADME/Pharmacokinetics |
Pharmacokinetic studies in animals and humans show that Dapaconazole is poorly absorbed after topical application, with minimal systemic exposure. After oral administration in rats, the compound has a half-life of ~4 hours and moderate bioavailability (~30%). In humans, topical application results in plasma concentrations below the limit of quantification, minimizing systemic side effects. The compound is metabolized by CYP3A4.
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| Toxicity/Toxicokinetics |
Toxicology studies indicate a good safety profile. In repeated-dose topical studies in rabbits and minipigs, no skin irritation or sensitization was observed. Oral acute toxicity in rats showed an LD50 > 2000 mg/kg. In Phase II trials, no treatment-related serious adverse events were reported. The compound is not mutagenic in Ames test. However, as an azole, hepatotoxicity remains a theoretical concern.
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| References | |
| Additional Infomation |
Dapaconazole has been used in trials to study the treatment of athlete's foot.
Dapaconazole is an experimental antifungal agent with the INN name Dapaconazole, molecular formula C19H15Cl2F3N2O, and molecular weight 415.24. It has been developed as a tosylate salt for topical use. The compound completed Phase II trials for pityriasis versicolor and is not yet approved. It is available for research purposes only and not for clinical use outside trials. |
| Molecular Formula |
C19H15CL2F3N2O
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|---|---|
| Molecular Weight |
415.236413240433
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| Exact Mass |
414.051
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| Elemental Analysis |
C, 54.96; H, 3.64; Cl, 17.07; F, 13.73; N, 6.75; O, 3.85
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| CAS # |
1269726-67-1
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| PubChem CID |
51001696
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| Appearance |
Off-white to yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
512.8±50.0 °C at 760 mmHg
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| Flash Point |
263.9±30.1 °C
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| Vapour Pressure |
0.0±1.3 mmHg at 25°C
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| Index of Refraction |
1.565
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| LogP |
5.3
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
27
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| Complexity |
461
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C=C(C=CC=1C(CN1C=NC=C1)OCC1C=CC(C(F)(F)F)=CC=1)Cl
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| InChi Key |
FUAHXHWSMYFWGE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H15Cl2F3N2O/c20-15-5-6-16(17(21)9-15)18(10-26-8-7-25-12-26)27-11-13-1-3-14(4-2-13)19(22,23)24/h1-9,12,18H,10-11H2
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| Chemical Name |
1-[2-(2,4-dichlorophenyl)-2-[[4-(trifluoromethyl)phenyl]methoxy]ethyl]imidazole
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| Synonyms |
Dapaconazole
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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 : ~100 mg/mL (~240.82 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.02 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (6.02 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.02 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4082 mL | 12.0412 mL | 24.0825 mL | |
| 5 mM | 0.4816 mL | 2.4082 mL | 4.8165 mL | |
| 10 mM | 0.2408 mL | 1.2041 mL | 2.4082 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT03359070 | Completed | Drug:Dapaconazole Drug:Miconazole Nitrate |
Tinea Cruris | Galeno Desenvolvimento de Pesquisas Clínicas |
January 29, 2014 | Phase 2 |
| NCT03320486 | Completed | Drug:Dapaconazole Drug:Ketoconazole |
Tinea Pedis | Biolab Sanus Farmaceutica | November 1, 2017 | Phase 3 |
| NCT02606383 | Withdrawn | Drug:Dapaconazole Drug:Ketoconazole |
Tinea Pedis | Biolab Sanus Farmaceutica | June 2016 | Phase 3 |
| NCT02824926 | Completed | Drug:Dapaconazole Drug:Ketoconazole |
Tinea Pedis | Gilberto De Nucci | July 2014 | Phase 2 |
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