Fumagillol
(Synonyms: 烟曲霉醇,(-)-Fumagillol) 目录号 : GC62220
Fumagillol 是 fumagillin 的直接前体。Fumagillin 作为一种抗菌药物，是一种有效的选择性血管生成抑制剂。
Cas No.:108102-51-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Fumagillol is a direct precursor of fumagillin. Fumagillin, as an antimicrobial agent, is a potent and selective inhibitor of angiogenesis[1].
Fumagillol derivatives have no significant cytotoxic effect on CHO cells[1].
[1]. Bedel, O., et al. "Syntheses of antiangiogenic or cytotoxic natural products: Fumagillin and bengacarboline" Pure and Applied Chemistry, vol. 77, no. 7, 2005, pp. 1139-1152.
| Cas No. | 108102-51-8 | SDF | |
| 别名 | 烟曲霉醇,(-)-Fumagillol | ||
| 分子式 | C16H26O4 | 分子量 | 282.38 |
| 溶解度 | DMSO : 100 mg/mL (354.13 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 | 3.5413 mL | 17.7066 mL | 35.4133 mL |
| 5 mM | 0.7083 mL | 3.5413 mL | 7.0827 mL |
| 10 mM | 0.3541 mL | 1.7707 mL | 3.5413 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。
Discovery and Preclinical Development of Antigiardiasis Fumagillol Derivatives
Antimicrob Agents Chemother 2020 Sep 21;64(10):e00582-20.PMID:32778548DOI:10.1128/AAC.00582-20.
Giardiasis, caused by the intestinal parasite Giardia lamblia, is a severe diarrheal disease, endemic in poverty-stricken regions of the world, and also a common infection in developed countries. The available therapeutic options are associated with adverse effects, and G. lamblia resistance to the standard-of-care drugs is spreading. Fumagillin, an antimicrosporidiosis drug, is a therapeutic agent with potential for the treatment of giardiasis. However, it exhibits considerable, albeit reversible, toxicity when used to treat immunocompromised microsporidiosis patients. Fumagillin is also a highly unstable compound. To address these liabilities, we designed and synthesized stable Fumagillol derivatives with lower levels of permeation across polarized epithelial Caco-2 cells and better potency against G. lamblia trophozoites than fumagillin. Metronidazole-resistant G. lamblia strains were also susceptible to the new Fumagillol derivatives. In addition, these compounds were more potent against the amebiasis-causing parasite Entamoeba histolytica than fumagillin. Two compounds exhibited better thermal and acid stability than fumagillin, which should prolong the drug shelf life and reduce compound degradation in the stomach. Studies with a mouse model of giardiasis with the most stable compound, 4-(((((3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl)oxy)carbonyl)amino)benzoic acid (compound 9), revealed that it had better efficacy (effective dose [ED]) than fumagillin at both the fully curative dose (the 100% ED) of 6.6 mg/kg of body weight and a 50% ED of 0.064 mg/kg. Plasma pharmacokinetics revealed the slow absorption of compound 9 through the gut, consistent with the in vitro characterization in Caco-2 cells. An acute-dose study yielded a maximum tolerated dose (MTD) of 1,500 mg/kg, 227-fold higher than the fully curative dose. Thus, along with improved stability, compound 9 also exhibited an excellent therapeutic window.
Three new Fumagillol analogues and antifungal activity from Aspergillus fumigatus cocultured with Paraphaeosphaeria sp
Fitoterapia 2023 Mar;165:105395.PMID:36539067DOI:10.1016/j.fitote.2022.105395.
Two fungi Aspergillus fumigatus YXG-12-2, and Paraphaeosphaeria sp. YXG-18 were isolated from medicinal plant Ginkgo biloba. The interaction of endophytes and host could induce the productions of antifungal metabolites against pathogens for the plant resistance. Three new Fumagillol analogues, fumiparaphines A-C were isolated from A. fumigatus cocultured with Paraphaeosphaeria sp. in host medium. New compounds 2, and 3 had the similar Fumagillol structures with tetrahydrofuran or tetrahydropyrane residue. The structures were established by 1D, 2D NMR, mass spectrometry, and calculated ECD spectra. Fumiparaphine A (1) indicated significant antifungal activity against the phytopathogen Alternaria alternata with MIC of 2 μg/mL.
A Concise Synthesis of Fumagillol
Angew Chem Int Ed Engl 1999 Apr 1;38(7):971-974.PMID:29711854DOI:10.1002/(SICI)1521-3773(19990401)38:7<971::AID-ANIE971>3.0.CO;2-W.
A 13-step synthesis of (±)-fumagillol (1), the direct precursor of the potent angiogenesis inhibitors TNP-470 and fumagillin, from crotonaldehyde, diethylamine, and acrolein (see the scheme) has been achieved. The synthesis features a remarkable hetero-Claisen rearrangement. Small-molecule inhibitors of angiogenesis are promising chemotherapeutic agents for the treatment of cancer and inflammatory diseases.
Remodeling of Fumagillol: discovery of an oxygen-directed oxidative Mannich reaction
Org Lett 2014 Feb 7;16(3):792-5.PMID:24410175DOI:10.1021/ol4035269.
An efficient, two-step construction of highly complex alkaloid-like compounds from the natural product Fumagillol is described. This approach, which mimics a biosynthetic cyclase/oxidase sequence, allows for rapid and efficient structure elaboration of the basic Fumagillol scaffold with a variety of readily available coupling partners. Mechanistic experiments leading to the discovery of an oxygen-directed oxidative Mannich reaction are also described.
Remodelling of the natural product Fumagillol employing a reaction discovery approach
Nat Chem 2011 Dec;3(12):969-73.PMID:22213919DOI:10.1038/nchem.1178.
In the search for new biologically active molecules, diversity-oriented synthetic strategies break through the limitation of traditional library synthesis by sampling new chemical space. Many natural products can be regarded as intriguing starting points for diversity-oriented synthesis, wherein stereochemically rich core structures may be reorganized into chemotypes that are distinctly different from the parent structure. Ideally, to be suited to library applications, such transformations should be general and involve few steps. With this objective in mind, the highly oxygenated natural product Fumagillol has been successfully remodelled in several ways using a reaction-discovery-based approach. In reactions with amines, excellent regiocontrol in a bis-epoxide opening/cyclization sequence can be obtained by size-dependent interaction of an appropriate catalyst with the parent molecule, forming either perhydroisoindole or perhydroisoquinoline products. Perhydroisoindoles can be further remodelled by cascade processes to afford either morpholinone or bridged 4,1-benzoxazepine-containing structures.