Dapaconazole
(Synonyms: 1-[2-(2,4-二氯苯基)-2-[[4-(三氟甲基)苯基]甲氧基]乙基]-1H-咪唑) 目录号 : GC62304
Dapaconazole 作为一种抗真菌化合物，抑制 sterol 14α-demethylase cytochrome P450 活性的 IC50 值为 1.4 μM。
Cas No.:1269726-67-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Dapaconazole, as an antifungal agent, inhibits sterol 14α-demethylase cytochrome P450 activity with an IC50 of 1.4 μM[1].
Dapaconazole inhibits sterol 14α-demethylase cytochrome P450 activity with an IC50 of 1.4 ± 0.3 μM[1].
Dapaconazole (20 mg/kg; p.o.) shows that the bioavailability is 97.3 %[1].
[1]. Juliana SP, et al. Pharmacokinetics of Dapaconazole, A Novel Antifungal Agent, in Beagle Dogs and Inhibition of Cytochrome P450 Family 51. J Eur Acad Dermatol Venereol. 2018 Jun 10.
| Cas No. | 1269726-67-1 | SDF | |
| 别名 | 1-[2-(2,4-二氯苯基)-2-[[4-(三氟甲基)苯基]甲氧基]乙基]-1H-咪唑 | ||
| 分子式 | C19H15Cl2F3N2O | 分子量 | 415.24 |
| 溶解度 | DMSO : 100 mg/mL (240.82 mM; Need ultrasonic) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Prospective Prediction of Dapaconazole Clinical Drug-Drug Interactions Using an In Vitro to In Vivo Extrapolation Equation and PBPK Modeling
Pharmaceuticals (Basel) 2022 Dec 26;16(1):28.PMID:36678526DOI:10.3390/ph16010028.
This study predicted Dapaconazole clinical drug−drug interactions (DDIs) over the main Cytochrome P450 (CYP) isoenzymes using static (in vitro to in vivo extrapolation equation, IVIVE) and dynamic (PBPK model) approaches. The in vitro inhibition of main CYP450 isoenzymes by Dapaconazole in a human liver microsome incubation medium was evaluated. A Dapaconazole PBPK model (Simcyp version 20) in dogs was developed and qualified using observed data and was scaled up for humans. Static and dynamic models to predict DDIs following current FDA guidelines were applied. The in vitro Dapaconazole inhibition was observed for all isoforms investigated, including CYP1A2 (IC50 of 3.68 µM), CYP2A6 (20.7 µM), 2C8 (104.1 µM), 2C9 (0.22 µM), 2C19 (0.05 µM), 2D6 (0.87 µM), and 3A4 (0.008−0.03 µM). The dynamic (PBPK) and static DDI mechanistic model-based analyses suggest that Dapaconazole is a weak inhibitor (AUCR > 1.25 and <2) of CYP1A2 and CYP2C9, a moderate inhibitor (AUCR > 2 and <5) of CYP2C8 and CYP2D6, and a strong inhibitor (AUCR ≥ 5) of CYP2C19 and CYP3A, considering a clinical scenario. The results presented may be a useful guide for future in vivo and clinical Dapaconazole studies.
In vitro metabolism of the new antifungal Dapaconazole using liver microsomes
Drug Metab Pharmacokinet 2022 Dec;47:100475.PMID:36370616DOI:10.1016/j.dmpk.2022.100475.
Dapaconazole is a new antifungal imidazole that has been shown a high efficacy against several pathogenic fungi. This study aimed to investigate the interspecies variation in the in vitro metabolic profiles and in vivo hepatic clearance (CLH,in vivo) prediction of Dapaconazole using liver microsomes from male Sprague Dawley rat, male Beagle dog and mixed gender human using a liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) method. In addition, the produced metabolites were identified by ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectrometer (UHPLC-QTOF-MS/MS). The microsomal protein concentration of 0.1 mg/mL and the incubation time of 10 min were employed for the kinetics determination, resulting in a sigmoidal kinetic profile for all species evaluated. The predicted CLH,in vivo was 6.5, 11.6 and 7.5 mL/min/kg for human, rat and dog, respectively. Furthermore, five metabolized products were identified. These findings provide preliminary information for understanding Dapaconazole metabolism and the interspecies differences in catalytic behaviours, supporting the choice of a suitable laboratory animal for future pharmacokinetics and metabolism studies.
Quantification of Dapaconazole in human plasma using high-performance liquid chromatography coupled to tandem mass spectrometry: application to a phase I study
J Chromatogr B Analyt Technol Biomed Life Sci 2014 May 1;958:102-7.PMID:24705538DOI:10.1016/j.jchromb.2014.01.053.
A simple, selective and sensitive method based on high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) has been developed for the determination of Dapaconazole in human plasma using tioconazole as internal standard. The drugs were extracted from plasma by liquid-liquid extraction with ether/hexane (80/20, v/v). The chromatography separation was performed on a Genesis(®) C18 reversed phase analytical column 4μm (100×2.1mm i.d.) with a mobile phase of methanol/acetonitrile/water (80/10/10, v/v/v)+ammonium acetate (0.5mM). Dapaconazole was quantified using a mass spectrometer with an electrospray source in the ESI positive mode (ES+) configured for multiple reaction monitoring (MRM) to monitor the transitions 415.1>159.2 and 387.0>131.0 for Dapaconazole and tioconazole, respectively. The method had a chromatography run time of 3.8min and a linear calibration curve over the range 0.2-100ng/mL (r=0.9998). The lower limit of quantification (LLOQ) was 0.2ng/mL. The precision and accuracy values of the assay were within ±10%. The stability tests indicate no significant degradation under the conditions of the experiment. This method was used for a phase I study of topical administration of Dapaconazole tosylate in healthy human male volunteers.
A randomized double-blind, non-inferiority Phase II trial, comparing Dapaconazole tosylate 2% cream with ketoconazole 2% cream in the treatment of Pityriasis versicolor
Expert Opin Investig Drugs 2015;24(11):1399-407.PMID:26419668DOI:10.1517/13543784.2015.1083009.
Objectives: The objective of this research was to evaluate the efficacy of a new antifungal imidazole, Dapaconazole tosylate, in the treatment of Pityriasis versicolor (PV). Design and methods: Sixty patients with clinical and mycological diagnosis of PV were randomly assigned to receive either 1 g Dapaconazole tosylate 2% cream or 1 g ketoconazole 2% cream. Treatments were applied once a day for 28 days. A dermatologist evaluated efficacy and safety daily, and weekly laboratorial tests were performed. The primary end point was a clinical and mycological cure of lesions after 28 days of treatment. The secondary end point was the time to clinical healing assessed by Kaplan-Meier analysis and Log-rank testing. Results: Fifty-three patients adhered to protocol rules. Clinical and mycological cure was achieved in 84.6% (22/26) and 92.6% (25/27) of patients treated with ketoconazole and Dapaconazole, respectively (difference [effect size] = 8.0%, Standard error of difference: 8.69%, 95% CI: -6.3 to 22.3%). Median time to healing was 23.5 and 21 days for ketoconazole and Dapaconazole, respectively (p = 0.126). Adverse events occurred only in ketoconazole-treated patients (13%; 4/30). Conclusion: Dapaconazole tosylate is non-inferior to ketoconazole when used at a dose of 20 mg/day for 28 consecutive days for the treatment of PV. Dapaconazole also demonstrated a good safety profile.