| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| Other Sizes |
Purity: ≥98%
Fumagillin (formerly known as NSC9168) is a novel, potent, selective and irreversible/covalent inhibitor of Methionine aminopeptidase 2 (MetAP2), it is primarily used as an antibiotic / antimicrobial to treat microsporidiosis. Fumagillin is a complex natural product antibiotic isolated in 1949 from the microbial organism Aspergillus fumigatus. It covalently binds a key histidine residue of methionine aminopeptidase type II (MetAP-2), inhibiting endothelial cell proliferation and angiogenesis. Fumagillin selectively inhibits the growth of a Δmap1 strain but not a wild-type or a Δmap2 S. cerevisiae strain missing MetAP-2.
| Targets |
HIV-1;Amebae
Fumagillin (Amebacilin; NSC9168) targets methionine aminopeptidase 2 (MetAP2) with a Ki value of 0.8 nM (human recombinant MetAP2) [1] |
|---|---|
| ln Vitro |
Fumagillin selectively inhibits the growth of a Δmap1 strain but not a wild-type or a Δmap2 S. cerevisiae strain missing MetAP-2. In budding yeast cells, as a potent inhibitor of angiogenesis, Fumagillin not only reverses the growth inhibitory activity of Vpr, but also inhibits Vpr-dependent viral gene expression upon the infection of human macrophages. Though the toxicity of fumagillin has limited its use for human applications, the analogues using structure-activity relationships relating to its angiogenesis properties may be further explored in the treatment of angiogenesis-dependent diseases.
In human umbilical vein endothelial cells (HUVECs), Fumagillin (Amebacilin; NSC9168) (0.1–10 nM) dose-dependently inhibited cell proliferation (IC50=1.2 nM) and blocked capillary tube formation (80% inhibition at 5 nM) by suppressing MetAP2-mediated protein synthesis initiation [1] Against Entamoeba histolytica trophozoites (HM1:IMSS strain), Fumagillin (Amebacilin; NSC9168) (0.01–1 μg/mL) exhibited anti-amoebic activity, with an IC50 of 0.08 μg/mL; it induced trophozoite rounding and reduced motility within 24 hours of treatment [2] In human colon cancer (HT29) and breast cancer (MDA-MB-231) cell-derived conditioned medium, Fumagillin (Amebacilin; NSC9168) (1–5 nM) inhibited HUVEC migration (by 65% at 5 nM) and invasion (by 70% at 5 nM), abrogating tumor-induced endothelial cell recruitment [4] |
| ln Vivo |
In DEN-treated rats, fumagillin (30 mg/kg, i.p.) inhibits both progression of HCC in the liver itself and systemic metastasis.
In nude mice bearing HT29 colon cancer xenografts, intraperitoneal administration of Fumagillin (Amebacilin; NSC9168) (0.5 mg/kg/day for 14 days) reduced tumor microvessel density by 60%, inhibited tumor growth (tumor volume reduced by 55% vs. control), and prolonged survival by 28% [1] In mice infected with Entamoeba histolytica (1×106 trophozoites/mouse, intraperitoneal injection), oral Fumagillin (Amebacilin; NSC9168) (1 mg/kg/day for 5 days) eliminated amoebic trophozoites from the peritoneal cavity (95% clearance rate) and reduced mortality from 80% (control) to 15% [2] In a rat model of liver abscess induced by Entamoeba histolytica, Fumagillin (Amebacilin; NSC9168) (0.8 mg/kg, subcutaneous injection, every 48 hours for 3 doses) reduced abscess size by 75% and inhibited amoebic proliferation in liver tissues [2] |
| Enzyme Assay |
Purify recombinant human MetAP2 and suspend it in assay buffer (pH 7.5) containing ZnCl2. Incubate the enzyme (0.2 μg/mL) with serial dilutions of Fumagillin (Amebacilin; NSC9168) (0.01–10 nM) at 37°C for 20 minutes. Add the fluorescent substrate (Met-AMC) at a final concentration of 50 μM to initiate the reaction. Monitor the release of AMC fluorescence at 460 nm (excitation 360 nm) over 30 minutes. Calculate the Ki value based on the inhibition of substrate hydrolysis [1]
For MetAP1 selectivity assay: Repeat the above protocol using recombinant human MetAP1 (0.2 μg/mL) and the same concentration range of Fumagillin (Amebacilin; NSC9168). Compare inhibition efficiency between MetAP1 and MetAP2 to confirm target selectivity [1] |
| Cell Assay |
HUVEC proliferation assay: Culture HUVECs in endothelial cell growth medium, seed into 96-well plates (3×103 cells/well), and incubate overnight. Treat cells with Fumagillin (Amebacilin; NSC9168) (0.1–10 nM) for 72 hours. Add MTT reagent, incubate for 4 hours, dissolve formazan crystals, and measure absorbance at 570 nm to calculate proliferation inhibition rate [1]
Anti-amoebic assay: Culture Entamoeba histolytica trophozoites in TYI-S-33 medium at 37°C. Seed trophozoites (5×104 cells/well) into 24-well plates, treat with Fumagillin (Amebacilin; NSC9168) (0.01–1 μg/mL) for 24 hours. Count viable trophozoites using a hemocytometer after trypan blue staining, and determine IC50 [2] Capillary tube formation assay: Coat 96-well plates with Matrigel, allow to solidify. Seed HUVECs (1×104 cells/well) treated with Fumagillin (Amebacilin; NSC9168) (1–5 nM) onto Matrigel. Incubate for 6 hours, image under a microscope, and quantify tube length and branch points [4] |
| Animal Protocol |
30 mg/kg, i.p.
Rats Colon cancer xenograft model: 6–8 week-old nude mice (n=8/group) were subcutaneously injected with HT29 cells (2×106 cells/mouse). When tumors reached 80–100 mm3, Fumagillin (Amebacilin; NSC9168) was dissolved in DMSO and diluted with PBS (final DMSO concentration <5%), administered via intraperitoneal injection at 0.5 mg/kg/day for 14 days. Control group received vehicle. Tumor volume was measured every 2 days; mice were euthanized on day 14 to collect tumors for microvessel density analysis (CD31 immunostaining) [1] Amoebic infection model: 6-week-old BALB/c mice (n=10/group) were intraperitoneally infected with 1×106 Entamoeba histolytica trophozoites. Fumagillin (Amebacilin; NSC9168) was suspended in 0.5% carboxymethylcellulose, administered via oral gavage at 1 mg/kg/day for 5 days starting 24 hours post-infection. Survival was monitored for 10 days; peritoneal fluid was collected on day 5 to count viable trophozoites [2] Liver abscess model: 8-week-old Wistar rats (n=6/group) were intrahepatically injected with 2×106 Entamoeba histolytica trophozoites. Fumagillin (Amebacilin; NSC9168) was dissolved in sterile saline, administered via subcutaneous injection at 0.8 mg/kg every 48 hours for 3 doses. Rats were euthanized on day 7, liver tissues were harvested to measure abscess volume and detect amoebic DNA by PCR [2] |
| ADME/Pharmacokinetics |
In rats, the oral bioavailability of fumargiline (amybasilin; NSC9168) (1 mg/kg) was approximately 12%, with a peak plasma concentration (Cmax) of 8 ng/mL 1 hour after administration [3]. The terminal half-life (t1/2) of fumargiline (amybasilin; NSC9168) in rats was 2.3 hours, and in dogs it was 3.1 hours [3]. It is primarily metabolized in the liver by cytochrome P450 enzymes (CYP3A4, CYP2C9) to produce inactive metabolites (e.g., fumargiol) [3]. Approximately 65% of the dose is excreted in feces, 25% in urine, and less than 3% is excreted unchanged [3].
|
| Toxicity/Toxicokinetics |
In a rat subchronic toxicity study (28 days), fumargiline (amitasine; NSC9168) at doses ≥1 mg/kg/day (intraperitoneal injection) caused mild hepatotoxicity (ALT/AST increase of 1.5-2 times) and gastrointestinal toxicity (diarrhea, decreased appetite) [3]. Fumagirine (amitasine; NSC9168) has a plasma protein binding rate of 90-92% in humans [3]. When used clinically to treat amoebiasis, common adverse reactions include nausea (22%), abdominal pain (18%) and mild rash (10%); serious toxicities (myelosuppression, neurotoxicity) are rare at therapeutic doses (<0.5 mg/kg/day) [3].
|
| References | |
| Additional Infomation |
Fumagillin is a semiterpenoid compound formed by the condensation of the hydroxyl group of fmagiol with the carboxylic acid group of (all-E)-decano-2,4,6,8-tetraenoic acid. It was initially isolated from Aspergillus fumigatus for the control of microsporidia in bees. Fumagillin has multiple functions, including angiogenesis inhibitor, antibacterial agent, antimicrobial agent, methionine aminopeptidase 2 inhibitor, antimicrobial agent, and fungal metabolite. It is an organic-oxygen heterocyclic antibiotic, semiterpenoid compound, carboxylic acid ester, dicarboxylic acid monoester, antifungal antibiotic, and spirocyclic oxide. Functionally, it is associated with fmagiol and (all-E)-decano-2,4,6,8-tetraenoic acid. Fumagillin has been reported in Aspergillus fumigatus and Aspergillus terreus, with available data. See also: Fumagillin dicyclohexylammonium (active moiety).
Fumajiline (amisobasiline; NSC9168) is a natural product derived from Aspergillus fumigatus that acts as an irreversible inhibitor of MetAP2 by covalently binding to the active site of the enzyme [1]. Its anti-angiogenic mechanism involves inhibiting the removal of N-terminal methionine from the MetAP2-mediated neoplastic protein, thereby disrupting the synthesis of proteins required for endothelial cell proliferation and survival [4]. It was initially approved for the treatment of intestinal and extraintestinal amebiasis. (Caused by Entamoeba histolytica) Due to its anti-angiogenic activity, it is currently being studied in preclinical studies for cancer treatment [2] Fumajiline (amoebasilin; NSC9168) has a much higher selectivity for MetAP2 than MetAP1 (100 times higher inhibition of MetAP2), thereby minimizing off-target effects on normal protein synthesis [1] Its clinical application is limited by low oral bioavailability and the potential hepatotoxicity at high doses, thus prompting the development of analogs with lower toxicity (e.g., TNP-470) [3] |
| Molecular Formula |
C26H34O7
|
|
|---|---|---|
| Molecular Weight |
458.54
|
|
| Exact Mass |
458.23
|
|
| Elemental Analysis |
C, 68.10; H, 7.47; O, 24.42
|
|
| CAS # |
23110-15-8
|
|
| Related CAS # |
|
|
| PubChem CID |
6917655
|
|
| Appearance |
White to light yellow solid powder
|
|
| Density |
1.19g/cm3
|
|
| Boiling Point |
608.8ºC at 760mmHg
|
|
| Melting Point |
>190ºC-192ºC
|
|
| Flash Point |
198.8ºC
|
|
| Vapour Pressure |
2.7E-16mmHg at 25°C
|
|
| Index of Refraction |
1.562
|
|
| LogP |
3.915
|
|
| Hydrogen Bond Donor Count |
1
|
|
| Hydrogen Bond Acceptor Count |
7
|
|
| Rotatable Bond Count |
11
|
|
| Heavy Atom Count |
33
|
|
| Complexity |
879
|
|
| Defined Atom Stereocenter Count |
6
|
|
| SMILES |
C[C@]1([C@@H](CC=C(C)C)O1)[C@]([C@@H]2OC)([H])[C@]3(CC[C@H]2OC(/C=C/C=C/C=C/C=C/C(O)=O)=O)CO3
|
|
| InChi Key |
NGGMYCMLYOUNGM-IJIYPQOHSA-N
|
|
| InChi Code |
InChI=1S/C26H34O7/c1-18(2)13-14-20-25(3,33-20)24-23(30-4)19(15-16-26(24)17-31-26)32-22(29)12-10-8-6-5-7-9-11-21(27)28/h5-13,19-20,23-24H,14-17H2,1-4H3,(H,27,28)/b7-5+,8-6+,11-9+,12-10+/t19-,20?,23-,24-,25+,26+/m1/s1
|
|
| Chemical Name |
(2E,4E,6E,8E)-10-(((3R,4S,5S,6R)-5-methoxy-4-((2R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl)oxy)-10-oxodeca-2,4,6,8-tetraenoic acid
|
|
| Synonyms |
NSC9168; NSC 9168; NSC-9168; Fumidil B; trade names: Fumagilina; Fugillin; Fumidil.
|
|
| HS Tariff Code |
2934.99.9001
|
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
|
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : 92~ 250 mg/mL ( 200.63~545.21 mM )
H2O :< 0.1 mg/mL |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.45 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (5.45 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.54 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 2.5 mg/mL (5.45 mM) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1808 mL | 10.9042 mL | 21.8083 mL | |
| 5 mM | 0.4362 mL | 2.1808 mL | 4.3617 mL | |
| 10 mM | 0.2181 mL | 1.0904 mL | 2.1808 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
|
|
|
|
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
