Fumagillin (T3D3760)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (1)XML
Targets (1)
Record Information
Version2.0
Creation Date2010-05-19 15:34:28 UTC
Update Date2014-12-24 20:26:30 UTC
Accession NumberT3D3760
Identification
Common NameFumagillin
ClassSmall Molecule
DescriptionFumagillin is a mycotoxin found in the fungus Aspergillus fumigatus. It is an antimicrobial agent and amebicide that has been used in the treatment of microsporidiosis and other infections, especially in immunodeficient patients. It also has been investigated as a angiogenesis inhibitor in the treatment of cancer. Since fumagillin is often used to treat microsporidiosis in bees, it can be found as a contaminant in honey. (7, 1)
Compound Type
  • Ester
  • Ether
  • Fungal Toxin
  • Mycotoxin
  • Natural Compound
  • Organic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
Flisint
Fugillin
Furnidil
Chemical FormulaC26H34O7
Average Molecular Mass458.544 g/mol
Monoisotopic Mass458.230 g/mol
CAS Registry Number23110-15-8
IUPAC Name10-({5-methoxy-4-[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
Traditional Name10-({5-methoxy-4-[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
SMILESCOC1C(CCC2(CO2)C1C1(C)OC1CC=C(C)C)OC(=O)C=CC=CC=CC=CC(O)=O
InChI IdentifierInChI=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+
InChI KeyInChIKey=NGGMYCMLYOUNGM-HCNIIHBUSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as medium-chain fatty acids. These are fatty acids with an aliphatic tail that contains between 4 and 12 carbon atoms.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassFatty Acyls
Sub ClassFatty acids and conjugates
Direct ParentMedium-chain fatty acids
Alternative Parents
Substituents
  • Medium-chain fatty acid
  • Branched fatty acid
  • Epoxy fatty acid
  • Fatty acid ester
  • Heterocyclic fatty acid
  • Dicarboxylic acid or derivatives
  • Unsaturated fatty acid
  • Alpha,beta-unsaturated carboxylic ester
  • Enoate ester
  • Carboxylic acid ester
  • Organoheterocyclic compound
  • Oxacycle
  • Ether
  • Oxirane
  • Dialkyl ether
  • Carboxylic acid
  • Carboxylic acid derivative
  • Organooxygen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Carbonyl group
  • Organic oxygen compound
  • Aliphatic heteropolycyclic compound
Molecular FrameworkAliphatic heteropolycyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0033 g/LALOGPS
logP4.61ALOGPS
logP4.05ChemAxon
logS-5.1ALOGPS
pKa (Strongest Acidic)4.88ChemAxon
pKa (Strongest Basic)-3.7ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area97.89 ŲChemAxon
Rotatable Bond Count11ChemAxon
Refractivity128.37 m³·mol⁻¹ChemAxon
Polarizability50.35 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0159-9673300000-a43a71934342e2d81c242021-09-23View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-052f-0332900000-dbca90b375ad880b144a2019-02-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-003r-8933200000-7bade8e4473f71d5104a2019-02-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0api-9330000000-279eeb3fc1f20ca317e02019-02-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-0322900000-58cf8a63cc58c075e4d92019-02-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0043-1972500000-e3d04b346f286d073bc82019-02-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0ar0-5930000000-5d443ae3a097edc0249c2019-02-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0ckc-0122900000-b567e79bf2790ea724102021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0adi-5602900000-3bc98ce62db96d9eda5f2021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00o9-9600000000-25647d72e12de463d8792021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0bua-0601900000-68432c0cedfb49e051032021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-053s-3955400000-54a900551830601be4e42021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-055k-5923000000-3224cf5581882fc125f72021-10-12View Spectrum
Toxicity Profile
Route of ExposureOral, dermal, inhalation, and parenteral (contaminated drugs). (6)
Mechanism of ToxicityFumagillin blocks blood vessel formation (angiogenesis) by inhibiting the enzyme methionine aminopeptidase 2. This prevents angiogenesis by arresting endothelial cells in the G1 phase of the cell cycle. Inhibition of angiogenesis can suppress tumor growth and metastasis. Methionine aminopeptidase 2 inhibition also blocks Wnt signaling, which plays a critical role in development, cell differentiation, and tumorigenesis. (2, 3)
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFumagillin is a mycotoxin found in the fungus Aspergillus fumigatus. It is an antimicrobial agent and amebicide that has been used in the treatment of microsporidiosis and other infections, especially in immunodeficient patients. It also has been investigated as a angiogenesis inhibitor in the treatment of cancer. Since fumagillin is often used to treat microsporidiosis in bees, it can be found as a contaminant in honey. (7, 1)
Minimum Risk LevelNot Available
Health EffectsFumagillin can be genotoxic, clastogenic, and cytotoxic. It may also cause thrombocytopenia, neutropenia and hyperlipasaemia. (1, 4, 5)
SymptomsFumagillin may cause abdominal cramps, vomiting, and diarrhea. (5)
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB02640
HMDB IDNot Available
PubChem Compound ID6436022
ChEMBL IDNot Available
ChemSpider IDNot Available
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkFumagillin
References
Synthesis Reference

Peterson, M.H., Goldstein, A.W. and Denison, F.W. Jr.; U.S. Patent 2,803,586; August 20, 1957; assigned to Abbott Laboratories.

MSDST3D3760.pdf
General References
  1. Stanimirovic Z, Stevanovic J, Bajic V, Radovic I: Evaluation of genotoxic effects of fumagillin by cytogenetic tests in vivo. Mutat Res. 2007 Mar 30;628(1):1-10. Epub 2007 Jan 14. [17258933 ]
  2. Hou L, Mori D, Takase Y, Meihua P, Kai K, Tokunaga O: Fumagillin inhibits colorectal cancer growth and metastasis in mice: in vivo and in vitro study of anti-angiogenesis. Pathol Int. 2009 Jul;59(7):448-61. doi: 10.1111/j.1440-1827.2009.02393.x. [19563408 ]
  3. Zhang Y, Yeh JR, Mara A, Ju R, Hines JF, Cirone P, Griesbach HL, Schneider I, Slusarski DC, Holley SA, Crews CM: A chemical and genetic approach to the mode of action of fumagillin. Chem Biol. 2006 Sep;13(9):1001-9. [16984890 ]
  4. Stevanovic J, Stanimirovic Z, Radakovic M, Stojic V: In vitro evaluation of the clastogenicity of fumagillin. Environ Mol Mutagen. 2008 Oct;49(8):594-601. doi: 10.1002/em.20409. [18613037 ]
  5. Molina JM, Goguel J, Sarfati C, Michiels JF, Desportes-Livage I, Balkan S, Chastang C, Cotte L, Maslo C, Struxiano A, Derouin F, Decazes JM: Trial of oral fumagillin for the treatment of intestinal microsporidiosis in patients with HIV infection. ANRS 054 Study Group. Agence Nationale de Recherche sur le SIDA. AIDS. 2000 Jul 7;14(10):1341-8. [10930148 ]
  6. Peraica M, Domijan AM: Contamination of food with mycotoxins and human health. Arh Hig Rada Toksikol. 2001 Mar;52(1):23-35. [11370295 ]
  7. Wikipedia. Fumagillin. Last Updated 1 April 2010. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Methionine aminopeptidase 2
General Function:
Poly(a) rna binding
Specific Function:
Cotranslationally removes the N-terminal methionine from nascent proteins. The N-terminal methionine is often cleaved when the second residue in the primary sequence is small and uncharged (Met-Ala-, Cys, Gly, Pro, Ser, Thr, or Val). The catalytic activity of human METAP2 toward Met-Val peptides is consistently two orders of magnitude higher than that of METAP1, suggesting that it is responsible for processing proteins containing N-terminal Met-Val and Met-Thr sequences in vivo.Protects eukaryotic initiation factor EIF2S1 from translation-inhibiting phosphorylation by inhibitory kinases such as EIF2AK2/PKR and EIF2AK1/HCR. Plays a critical role in the regulation of protein synthesis.
Gene Name:
METAP2
Uniprot ID:
P50579
Molecular Weight:
52891.145 Da
References
  1. Hou L, Mori D, Takase Y, Meihua P, Kai K, Tokunaga O: Fumagillin inhibits colorectal cancer growth and metastasis in mice: in vivo and in vitro study of anti-angiogenesis. Pathol Int. 2009 Jul;59(7):448-61. doi: 10.1111/j.1440-1827.2009.02393.x. [19563408 ]
  2. Zhang Y, Yeh JR, Mara A, Ju R, Hines JF, Cirone P, Griesbach HL, Schneider I, Slusarski DC, Holley SA, Crews CM: A chemical and genetic approach to the mode of action of fumagillin. Chem Biol. 2006 Sep;13(9):1001-9. [16984890 ]