Ravuconazole (BMS-207147)
(Synonyms: 雷夫康唑; BMS-207147; ER-30346) 目录号 : GC32116
A triazole antifungal
Cas No.:182760-06-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Animal experiment: | Mouse[1] Ravuconazole is prepared in 10% DMSO in 0.5% CMC.C. neoformans No. 3 is grown on an SDA plate at 30°Cfor 48 h, and challenge organisms are prepared in sterile saline. Mice (age, 5 weeks; n 5 10) are infected via the tail vein. Ravuconazole are orally administered, in a volume of 0.2 mL per dose, twice daily for 5 consecutive days starting 1 h after infection. Controls receive 10% DMSO in 0.5% CMC. Ravuconazole are administered at doses of 8 and 32 mg/kg. Mortality is recorded daily for 21 days of infection. Drug efficacy is assessed by determining the delay in mortality. Rats[3] The rats are orally infected three times at 48-h intervals with 0.1 mL of a saline suspension containing cells of C. albicansE81022. Ravuconazoleis orally administered, in a volume of 0.5 mL per dose, once daily for 3 consecutive days starting 2 days after the last infection. Control groups receive 10% DMSO in 0.5% CMC. Drugs are administered at doses of 1 and 4 mg/kg. Drug efficacy is assessed 5 days after the last infection by measuring the number of C. albicansorganisms in oral swabs. |
References: [1]. Hata K, et al. In vitro and in vivo antifungal activities of ER-30346, a novel oral triazole with a broad antifungal spectrum.Antimicrob Agents Chemother. 1996 Oct;40(10):2237-42. | |
Ravuconazole is an orally available triazole fungicide that potently inhibits the growth of a wide range of fungi (MICs range from 25 to 780 ng/ml).1,2 Like other azoles, ravuconazole inhibits cytochrome P450 (CYP) isoforms that are involved in ergosterol biosynthesis, interfering with the generation of the fungal and protozoan cell membranes.3 Ravuconazole specifically inhibits sterol 14α-demethylase (CYP51).4,5 As this enzyme is also important in the development of trypanosomes, ravuconazole is effective against T. cruzi infections in animal models of Chagas disease.4,5
1.Hata, K., Kimura, J., Miki, H., et al.In vitro and in vivo antifungal activities of ER-30346, a novel oral triazole with a broad antifungal spectrumAntimicrob. Agents Chemother.40(10)2237-2242(1996) 2.Hata, K., Kimura, J., Miki, H., et al.Efficacy of ER-30346, a novel oral triazole antifungal agent, in experimental models of aspergillosis, candidiasis, and cryptococcosisAntimicrob. Agents Chemother.40(10)2243-2247(1996) 3.Carillo-Mu?oz, A.J., Giusiano, G., Ezkurra, P.A., et al.Antifungal agents: mode of action in yeast cellsRev.Esp.Quimioter.19(2)130-139(2006) 4.Urbina, J.A., Payares, G., Sanoja, C., et al.In vitro and in vivo activities of ravuconazole on Trypanosoma cruzi, the causative agent of Chagas diseaseInt.J.Antimicrob.Agents21(1)27-38(2003) 5.Lepsheva, G.I.Design or screening of drugs for the treatment of Chagas disease: What shows the most promise?Expert Opin.Drug Discov.8(12)1479-1489(2013)
| Cas No. | 182760-06-1 | SDF | |
| 别名 | 雷夫康唑; BMS-207147; ER-30346 | ||
| Canonical SMILES | FC1=CC(F)=CC=C1[C@](CN2C=NC=N2)(O)[C@@H](C)C3=NC(C4=CC=C(C#N)C=C4)=CS3 | ||
| 分子式 | C22H17F2N5OS | 分子量 | 437.47 |
| 溶解度 | DMSO : ≥ 50 mg/mL (114.29 mM);Water : < 0.1 mg/mL (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 | 2.2859 mL | 11.4294 mL | 22.8587 mL |
| 5 mM | 0.4572 mL | 2.2859 mL | 4.5717 mL |
| 10 mM | 0.2286 mL | 1.1429 mL | 2.2859 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。
Nonclinical pharmacokinetics of BMS-292655, a water-soluble prodrug of the antifungal ravuconazole
Biopharm Drug Dispos2008 Jul;29(5):270-9.PMID:18548464DOI:10.1002/bdd.612.
The phosphate ester, BMS-292655, was developed as a water-soluble prodrug of the antifungal agent, Ravuconazole (BMS-207147). BMS-292655 was comparatively stable in rat, beagle dog, cynomolgus monkey and human plasma, but was hydrolysed upon incubation with liver S9 preparations from all species. The major product in rat, monkey and human S9 was BMS-207147, while in dog S9, the intermediate ester, BMS-300043, predominated. BMS-300043 itself was more stable in dog S9 than in S9 preparations from the other species. Intravenous administration of BMS-292655 to rats, beagle dogs and cynomolgus monkeys indicated species differences in the extent of formation of BMS-207147 (monkeys>rats>dogs). The lower overall generation of BMS-207147 in dogs was consistent with the presence of circulating plasma levels of BMS-300043. BMS-300043 was present in monkey plasma but not detectable in rat plasma. The conversion of BMS-292655 to BMS-207147 in the presence of human S9 indicated the potential for BMS-292655 to function as a BMS-207147 prodrug in humans. The similarity in the hydrolysis of BMS-292655 when incubated with human and monkey S9 in vitro, coupled with the effective release of BMS-207147 from BMS-292655 upon i.v. administration to monkeys, is consistent with this conclusion.
Efficacy of Ravuconazole (BMS-207147) in a guinea pig model of disseminated aspergillosis
J Antimicrob Chemother2002 Feb;49(2):353-7.PMID:11815579DOI:10.1093/jac/49.2.353.
Ravuconazole (BMS-207147, ER-30346), an oral triazole, was evaluated in an immunosuppressed temporarily neutropenic guinea pig model of invasive aspergillosis. In this model, guinea pigs were immunosuppressed with triamcinolone 20 mg/kg sc od beginning 4 days before challenge and made neutropenic with cyclophosphamide 300 mg/kg ip 1 day before challenge. Treatments of ravuconazole 5, 10 and 25 mg/kg po od were compared with itraconazole 2.5 and 5.0 mg/kg po bd and amphotericin B 1.25 mg/kg ip od. Treatment began 24 h after lethal intravenous challenge with Aspergillus fumigatus and continued for 5 days. Mortality occurred in eight of eight untreated control animals versus none of eight treated with ravuconazole 5 or 10 mg/kg/day or itraconazole 10 mg/kg/day. Mortality occurred in one of eight animals treated with ravuconazole 25 mg/kg/day, one of eight with amphotericin B and two of eight treated with itraconazole 5 mg/kg/day. Compared with controls, each of the antifungals examined significantly reduced the tissue burden in liver and brain, although only the highest doses of the azole drugs and amphotericin B significantly reduced tissue burden in the kidney. All three doses of ravuconazole improved survival and also reduced the tissue burden of ASPERGILLUS: In this model of invasive aspergillosis, ravuconazole showed significant activity and may be a useful compound in human disease.
In vitro activities of Ravuconazole (BMS-207147) against 541 clinical isolates of Cryptococcus neoformans
Antimicrob Agents Chemother2000 Oct;44(10):2883-6.PMID:10991880DOI:10.1128/AAC.44.10.2883-2886.2000.
The in vitro activities of the new triazole, Ravuconazole (BMS-207147), were compared to those of fluconazole and itraconazole against 541 clinical isolates of Cryptococcus neoformans. Isolates were obtained from cerebrospinal fluid (396), blood (116), and miscellaneous clinical specimens (29). Overall, ravuconazole (MIC at which 90% of the isolates are inhibited [MIC(90)], 0.25 microg/ml) was more active than either itraconazole (MIC(90), 0.5 microg/ml) or fluconazole (MIC(90), 8 microg/ml). Among the isolates inhibited by > or =16 microg of fluconazole/ml, 90.2% were inhibited by < or =1 microg of ravuconazole/ml. On the basis of our findings and the favorable pharmacokinetic properties of ravuconazole, we suggest that ravuconazole may be useful for the treatment of infectious diseases due to C. neoformans and that further clinical studies to confirm these promising in vitro results are warranted.
In vitro antifungal activity of BMS-207147 and itraconazole against yeast strains that are non-susceptible to fluconazole
Diagn Microbiol Infect Dis1999 Oct;35(2):163-7.PMID:10579098DOI:10.1016/s0732-8893(99)00063-2.
The activities of itraconazole and the new triazole BMS-207147 were determined against Candida strains that were susceptible-dose dependent (fluconazole MICs 16 to 32 micrograms/mL) or resistant (MICs > or = 64 micrograms/mL) to fluconazole. These strains included clinical isolates of Candida krusei, Candida glabrata, and Candida albicans. In addition, 16 isogenic, genetically characterized isolates of C. albicans, with progressively decreased susceptibility to fluconazole, were tested. BMS-207147 MICs to C. krusei, a species considered intrinsically resistant to fluconazole, were at 0.13 to 0.5 microgram/mL. The population distribution of the fluconazole-nonsusceptible C. glabrata was bimodal with BMS-207147/itraconazole MICs at 0.5 to 2 micrograms/mL and > or = 16 micrograms/mL. The BMS-207147 MICs to the majority of fluconazole-nonsusceptible C. albicans strains tested were < or = 1 microgram/mL. The activity of BMS-207147 was minimally affected by overexpression of the gene encoding the efflux pump MDR1, but MIC increases were observed with changes in ERG11 and with overexpression of the CDR transporter gene. Nonetheless, BMS-207147 can be active against C. albicans mutants containing cumulative resistance mechanisms to azoles. In other words, fluconazole-resistant candidal strains may be susceptible to BMS-207147.
In vitro activity of a new oral triazole, BMS-207147 (ER-30346)
Antimicrob Agents Chemother1998 Feb;42(2):313-8.PMID:9527778DOI:10.1128/AAC.42.2.313.
The antifungal activity of BMS-207147 (also known as ER-30346) was compared to those of itraconazole and fluconazole against 250 strains of fungi representing 44 fungal species. MICs were determined by using the National Committee for Clinical Laboratory Standards (NCCLS)-recommended broth macrodilution method for yeasts, which was modified for filamentous fungi. BMS-207147 was about two- to fourfold more potent than itraconazole and about 40-fold more active than fluconazole against yeasts. With the NCCLS-recommended resistant MIC breakpoints of > or = 1 microg/ml for itraconazole and of > or = 64 microg/ml for fluconazole against Candida spp., itraconazole and fluconazole were inactive against strains of Candida krusei and Candida tropicalis. In contrast, all but 9 (all C. tropicalis) of the 116 Candida strains tested had BMS-207147 MICs of < 1 microg/ml. The three triazoles were active against about half of the Candida glabrata strains and against all of the Cryptococcus neoformans strains tested. The three triazoles were fungistatic to most yeast species, except for BMS-207147 and itraconazole, which were fungicidal to cryptococci. BMS-207147 and itraconazole were inhibitory to most aspergilli, and against half of the isolates, the activity was cidal. BMS-207147 and itraconazole were active, though not cidal, against most hyaline Hyphomycetes (with the exception of Fusarium spp. and Pseudallescheria boydii), dermatophytes, and the dematiaceous fungi and inactive against Sporothrix schenckii and zygomycetes. Fluconazole, on the other hand, was inactive against most filamentous fungi with the exception of dermatophytes other than Microsporum gypseum. Thus, the spectrum and potency of BMS-207147 indicate that it should be a candidate for clinical development.