Fosravuconazole L-lysine ethanolate
(Synonyms: 磷酸咪康唑L-赖氨酸乙醇,BMS-379224 L-lysine ethanolate; E-1224 L-lysine ethanolate) 目录号 : GC62323
Fosravuconazole L-lysine ethanolate (BMS-379224 L-lysine ethanolate)，Ravuconazole 的前药，是一种具有口服活性的广谱抗真菌剂。Fosravuconazole L-lysine ethanolate 可用于念珠菌病，灰指甲病和寄生虫病的研究。
Cas No.:914361-45-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >96.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Fosravuconazole L-lysine ethanolate (BMS-379224 L-lysine ethanolate), a prodrug of Ravuconazole, is an orally active broad spectrum antifungal agent. Fosravuconazole L-lysine ethanolate can be used for candidiasis, onychomycosis and parasitemia research[1][2][3].
Fosravuconazole has potent in vitro antifungal activity against a wide range of fungal species, including Candida, Aspergillus, and Trichophyton species[1].
Fosravuconazole (E-1224; 10-50 mg/kg; oral administration; daily; for 20 days) treatment suppresses the parasitemia and prevents death in mice infected with the T. cruzi Y strain[3].
[1]. Shinichi Watanabe, et al. Efficacy and safety of fosravuconazole L-lysine ethanolate, a novel oral triazole antifungal agent, for the treatment of onychomycosis: A multicenter, double-blind, randomized phase III study. J Dermatol. 2018 Oct;45(10):1151-1159.
[2]. Katsura Hata, et al. Development of E1224 by leveraging a strategic partnership for the medicines creation against neglected tropical diseases. Parasitol Int. 2020 Dec 25;81:102278.
[3]. LÍvia de Figueiredo Diniz, et al. Outcome of E1224-Benznidazole Combination Treatment for Infection with a Multidrug-Resistant Trypanosoma cruzi Strain in Mice. Antimicrob Agents Chemother. 2018 May 25;62(6):e00401-18.
| Cas No. | 914361-45-8 | SDF | |
| 别名 | 磷酸咪康唑L-赖氨酸乙醇,BMS-379224 L-lysine ethanolate; E-1224 L-lysine ethanolate | ||
| 分子式 | C31H40F2N7O8PS | 分子量 | 739.73 |
| 溶解度 | DMSO : 50 mg/mL (67.59 mM; Need ultrasonic)|Water : < 0.1 mg/mL (ultrasonic) (insoluble) | 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 | 1.3518 mL | 6.7592 mL | 13.5184 mL |
| 5 mM | 0.2704 mL | 1.3518 mL | 2.7037 mL |
| 10 mM | 0.1352 mL | 0.6759 mL | 1.3518 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。
[Drug properties of Fosravuconazole L-lysine ethanolate (NAILIN® Capsules 100 mg), a new oral azole therapeutic for onychomycosis: an analysis based on non-clinical and clinical trial data]
Nihon Yakurigaku Zasshi 2019;153(2):79-87.PMID:30745518DOI:10.1254/fpj.153.79.
Ravuconazole is a fourth generation azole exerting strong antifungal activity, with low drug-drug interaction and hepatic dysfunction risks. Fosravuconazole L-lysine ethanolate (fosravuconazole; NAILIN® Capsules 100 mg) was developed as a ravuconazole prodrug. Ravuconazole exerts strong antifungal activity against various pathogenic fungi including dermatophytes and Candida. Through prodrug formation, pharmacokinetic improvement was achieved, and bioavailability after oral administration reached 100%. The plasma ravuconazole concentration became 10-35 times higher than with current oral anti-onychomycosis drugs, and showed good skin and nail tissue transition plus tissue retention. This improvement obtained with fosravuconazole reflects its superior pharmacokinetic properties. We conducted a clinical trial with fosravuconazole orally administered once a day (100 mg ravuconazole) for 12 weeks in Japanese onychomycosis patients. The ravuconazole concentration in nail tissues exceeded the MIC90 against dermatophytes, even after treatment completion. Furthermore, the placebo-controlled, double-blind, comparative trial showed significantly superior effects (at 48 weeks after starting treatment, with a complete cure rate of 59.4%, a marked clinical improvement rate of 83.1%, and a mycological cure rate by direct microscopy of 82.0%). The major adverse reactions were laboratory abnormalities and gastrointestinal disorders with no severe symptoms, suggesting good tolerability. Fosravuconazole has fewer drug-drug interactions, is not affected by food, and is also expected to improve medication adherence since the administration period is only 12 weeks and there is no drug-free period as required with pulse therapy. Thus, fosravuconazole has many favorable pharmacological properties and can reasonably be expected to become a new oral treatment option for onychomycosis.
Efficacy and safety of Fosravuconazole L-lysine ethanolate, a novel oral triazole antifungal agent, for the treatment of onychomycosis: A multicenter, double-blind, randomized phase III study
J Dermatol 2018 Oct;45(10):1151-1159.PMID:30156314DOI:10.1111/1346-8138.14607.
Fosravuconazole L-lysine ethanolate (F-RVCZ) is a prodrug of ravuconazole, a novel triazole antifungal agent, exerting broad and potent antifungal activity. The efficacy and safety of F-RVCZ, compared with a placebo, were investigated in a multicenter, double-blind, randomized study of Japanese onychomycosis patients with 25% or more clinical involvement of the target toenail. Subjects (n = 153) were randomly assigned to receive F-RVCZ (100 mg RVCZ, n = 101) or placebo (n = 52) p.o. once daily for 12 weeks. The primary end-point was the rate of complete cure (clinical cure [0% clinical involvement of the target toenail] plus mycological cure [negative potassium hydroxide examination]) at week 48 (36-week post-treatment visit). Secondary end-points were changes over time in the efficacy and mycological effect of F-RVCZ. Safety was also evaluated. The complete cure rate at week 48 was significantly higher with F-RVCZ (59.4%, 60/101) than the placebo (5.8%, 3/52) in the full analysis set (P < 0.001). The mycological cure rate at week 48 was also significantly higher with F-RVCZ (82.0%, 73/89) than the placebo (20.0%, 10/50, P < 0.001). Regarding safety, adverse events were observed in 83.2% (84/101) and 80.8% (42/52), and adverse drug reactions (ADR) in 23.8% (24/101) and 3.8% (2/52) of F-RVCZ and placebo subjects, respectively. ADR were mild to moderate in severity, with none being serious. F-RVCZ (equivalent to 100 mg ravuconazole) administrated once daily for 12 weeks was more effective than placebo and tolerable in patients with onychomycosis, suggesting it to be a promising drug for onychomycosis treatment.
A Case of Tinea Faciei, Tinea Corporis, and Tinea Unguium with Dermatophytoma Successfully Treated with Oral Fosravuconazole L-lysine ethanolate
Med Mycol J 2021;62(1):1-4.PMID:33642522DOI:10.3314/mmj.20-00015.
We present a 76-year-old Japanese male with tinea faciei, tinea corporis, and tinea unguium with dermatophytoma. We performed fungal culture and confirmed the causative fungus to be Trichophyton rubrum. We treated the patient using oral Fosravuconazole L-lysine ethanolate (F-RVCZ). More than one year has passed since the end of treatment, but there has been no recurrence. This case suggests that F-RVCZ is effective for tinea other than tinea unguium.
Treatment Outcome with Fosravuconazole for Onychomycosis
Mycopathologia 2021 May;186(2):259-267.PMID:33754205DOI:10.1007/s11046-021-00540-6.
Fosravuconazole L-lysine ethanolate (F-RVCZ), a ravuconazole prodrug, is a newly available agent with high expectations for efficacy in the treatment of onychomycosis. However, clinical data regarding the efficacy of F-RVCZ are limited because the drug was launched only in Japan in 2018. Therefore, we analyzed the outcome of F-RVCZ therapy in the treatment of onychomycosis at outpatient dermatology clinics in Japan. We examined data for 109 patients (68 male, 41 female) with varying clinical type, including total dystrophic onychomycosis and dermatophytoma, and a wide range of age groups, including the elderly. The complete cure rate at 12 weeks was 6.4% (7/109) and 67.9% (74/109) at the last visit (mean time to last visit: 32 ± 14.2 weeks). Mean rate of improvement in the affected nail area was 49.1 ± 23.3% at 12 weeks and 86.8 ± 22.4% at the last visit. Efficacy at 12 weeks and the last visit, respectively, was as follows: none, 4 cases and 1 case; slight, 35 cases and 4 cases; moderate, 51 cases and 21 cases; significant, 12 cases and 9 cases; complete cure, 7 cases and 74 cases. There were no serious adverse events. This retrospective survey was the first large-scale analysis of actual clinical practice outcomes and had minimal exclusions. Compared to previous reports, our results demonstrated excellent efficacy of F-RVCZ therapy in a variety of patients. Considering our results and the ease of oral administration (1 capsule/day for 12 weeks) and few adverse events, F-RVCZ therapy appears to be a useful option for the treatment of onychomycosis.
Development of E1224 by leveraging a strategic partnership for the medicines creation against neglected tropical diseases
Parasitol Int 2021 Apr;81:102278.PMID:33370607DOI:10.1016/j.parint.2020.102278.
Neglected tropical diseases (NTDs) are communicable diseases that are uncommon in developed countries but epidemic in developing countries in tropical and subtropical regions of the world. One of the important contributions expected of pharmaceutical companies is the development and provision of drugs effective against NTDs. Eisai's efforts toward improving global health have resulted in a rich portfolio of assets addressing six infectious diseases: malaria, tuberculosis, Chagas disease, lymphatic filariasis, leishmaniasis, and mycetoma. As the most advanced project, Eisai has developed E1224 (Fosravuconazole L-lysine ethanolate), which is available in both intravenous and oral formulations, and provides ravuconazole, an active form of fosravuconazole, with a long plasma half-life. The first clinical trials of E1224, for Chagas disease, have already been completed, led by the Drugs for Neglected Diseases initiative (DNDi). As a result, parasite clearance was observed with E1224 during the treatment phase, but parasite regrowth was observed after the end of drug administration, suggesting that the mechanism of action of E1224 on Trypanosoma cruzi is static rather than parasiticidal. On the other hand, a clinical trial for eumycetoma in collaboration with DNDi is ongoing supported by the Global Health Innovative Technology Fund, and is examining the efficacy of weekly treatment with E1224 versus the current standard of care, daily treatment with itraconazole. In this manner, Eisai will continue its drug-discovery research projects in collaboration with various PDPs and academia supported by funding agencies.