Enfumafungin
目录号 : GC61518
Enfumafungin，一种三萜糖苷，是从Hormonema内生物种的提取物中分离得到的。Enfumafungin是一种抗真菌化合物，可作为(1,3)-beta-D-葡聚糖合酶抑制剂作用在真菌细胞壁上。Enfumafungin对酵母和真菌（隐球菌除外）具有特异性，不抑制枯草芽孢杆菌的生长。
Cas No.:260979-95-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Enfumafungin, a triterpene glycoside, is isolated from extracts derived from an endophytic species of Hormonema. Enfumafungin is an antifungal compound that is acting on the fungal cell wall, as the (1,3)-beta-D-glucan synthase inhibitor. Enfumafungin is specific for yeasts and fungi (excluding Cryptococcus) and does not inhibit the growth of Bacillus subtilis[1][2].
Enfumafungin (24-48 h) has MICs of less than 0.5 μg/mL against the Candida and Aspergillus species tested and it is inactive against Cryptococcus, including the decapsulated form (MY2062)[1].
Enfumafungin (50-200 mg/kg; i.p. twice daily for 2 days) produces a significant decrease in the number of c.f.u. in kidneys of mice challenged with C. albicans, with an ED90 of 90 mg/kg[1].
[1]. PelÁez F, et, al. The discovery of enfumafungin, a novel antifungal compound produced by an endophytic Hormonema species biological activity and taxonomy of the producing organisms. Syst Appl Microbiol. 2000 Oct;23(3):333-43. [2]. Onishi J, et, al. Discovery of novel antifungal (1,3)-beta-D-glucan synthase inhibitors. Antimicrob Agents Chemother. 2000 Feb;44(2):368-77.
| Cas No. | 260979-95-1 | SDF | |
| Canonical SMILES | OC(OC1)[C@@]([C@](CC2)([H])[C@@]1([C@H]3O[C@]([C@@H]([C@H]4O)O)([H])O[C@@H]([C@H]4O)CO)C)(C[C@H]3OC(C)=O)C([C@@]2([H])[C@]5(CC[C@]6(C)[C@H](C)C(C)C)C)=CC[C@]5([C@@H]6C(O)=O)C | ||
| 分子式 | C38H60O12 | 分子量 | 708.88 |
| 溶解度 | 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 | 1.4107 mL | 7.0534 mL | 14.1068 mL |
| 5 mM | 0.2821 mL | 1.4107 mL | 2.8214 mL |
| 10 mM | 0.1411 mL | 0.7053 mL | 1.4107 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。
Enfumafungin synthase represents a novel lineage of fungal triterpene cyclases
Environ Microbiol 2018 Sep;20(9):3325-3342.PMID:30051576DOI:10.1111/1462-2920.14333.
Enfumafungin is a glycosylated fernene-type triterpenoid produced by the fungus Hormonema carpetanum. Its potent antifungal activity, mediated by its interaction with β-1,3-glucan synthase and the fungal cell wall, has led to its development into the semi-synthetic clinical candidate, ibrexafungerp (=SCY-078). We report on the preliminary identification of the Enfumafungin biosynthetic gene cluster (BGC) based on genome sequencing, phylogenetic reconstruction, gene disruption, and cDNA sequencing studies. Enfumafungin synthase (efuA) consists of a terpene cyclase domain (TC) fused to a glycosyltransferase (GT) domain and thus represents a novel multifunctional enzyme. Moreover, the TC domain bears a phylogenetic relationship to bacterial squalene-hopene cyclases (SHC) and includes a typical DXDD motif within the active centre suggesting that efuA evolved from SHCs. Phylogenetic reconstruction of the GT domain indicated that this portion of the fusion gene originated from fungal sterol GTs. Eleven genes flanking efuA are putatively involved in the biosynthesis, regulation, transport and self-resistance of Enfumafungin and include an acetyltransferase, three P450 monooxygenases, a dehydrogenase, a desaturase and a reductase. A hypothetical scheme for Enfumafungin assembly is proposed in which the E-ring is oxidatively cleaved to yield the four-ring system of Enfumafungin. EfuA represents the first member of a widespread lineage of fungal SHCs.
Enfumafungin derivative MK-3118 shows increased in vitro potency against clinical echinocandin-resistant Candida Species and Aspergillus species isolates
Antimicrob Agents Chemother 2014;58(2):1248-51.PMID:24323472DOI:10.1128/AAC.02145-13.
MK-3118 is as an orally active new antifungal in the early stage of clinical development that inhibits the biosynthesis of β-(1,3)-glucan. We evaluated the in vitro activity of this compound against wild-type and echinocandin-resistant (ER) isolates containing mutations in the FKS gene(s) of Candida spp. and Aspergillus spp. MK-3118 demonstrated enhanced efficacy for most C. albicans and C. glabrata ER isolates relative to caspofungin, with decreased MICs and half-maximal inhibitory concentrations (IC50s).
Cell Wall-Modifying Antifungal Drugs
Curr Top Microbiol Immunol 2020;425:255-275.PMID:31875267DOI:10.1007/82_2019_188.
Antifungal therapy is a critical component of patient management for invasive fungal diseases. Yet, therapeutic choices are limited as only a few drug classes are available to treat systemic disease, and some infecting strains are resistant to one or more drug classes. The ideal antifungal inhibits a fungal-specific essential target not present in human cells to avoid off-target toxicities. The fungal cell wall is an ideal drug target because its integrity is critical to cell survival and a majority of biosynthetic enzymes and wall components is unique to fungi. Among currently approved antifungal agents and those in clinical development, drugs targeting biosynthetic enzymes of the cell wall show safe and efficacious antifungal properties, which validates the cell wall as a target. The echinocandins, which inhibit β-1,3-glucan synthase, are recommended as first-line therapy for Candida infections. Newer cell wall-active drugs in clinical development encompass next-generation glucan synthase inhibitors including a novel echinocandin and an Enfumafungin, an inhibitor of Gwt1, a key component of GPI anchor protein biosynthesis, and a classic inhibitor of chitin biosynthesis. As the cell wall is rich in potential drug discovery targets, it is primed to help deliver the next generation of antifungal drugs.
Novel orally active inhibitors of β-1,3-glucan synthesis derived from Enfumafungin
Bioorg Med Chem Lett 2015 Dec 15;25(24):5813-8.PMID:26542966DOI:10.1016/j.bmcl.2015.10.011.
The clinical success of the echinocandins, which can only be administered parentally, has validated β-1,3-glucan synthase (GS) as an antifungal target. Semi-synthetic modification of Enfumafungin, a triterpene glycoside natural product, was performed with the aim of producing a new class of orally active GS inhibitors. Replacement of the C2 acetoxy moiety with various heterocycles did not improve GS or antifungal potency. However, replacement of the C3 glycoside with an aminoether moiety dramatically improved oral pharmacokinetic (PK) properties while maintaining GS and antifungal potency. Installing an aminotetrazole at C2 in conjunction with an N-alkylated aminoether at C3 produced derivatives with significantly improved GS and antifungal potency that exhibited robust oral efficacy in a murine model of disseminated candidiasis.
Synthesis of antifungal glucan synthase inhibitors from Enfumafungin
J Org Chem 2012 Apr 6;77(7):3297-310.PMID:22423625DOI:10.1021/jo300046v.
An efficient, new, and scalable semisynthesis of glucan synthase inhibitors 1 and 2 from the fermentation product Enfumafungin 3 is described. The highlights of the synthesis include a high-yielding ether bond-forming reaction between a bulky sulfamidate 17 and alcohol 4 and a remarkably chemoselective, improved palladium(II)-mediated Corey-Yu allylic oxidation at the highly congested C-12 position of the Enfumafungin core. Multi-hundred gram quantities of the target drug candidates 1 and 2 were prepared, in 12 linear steps with 25% isolated yield and 13 linear steps with 22% isolated yield, respectively.