Fumagillin

Structural formula
General
Non-proprietary name	Fumagillin
other names	(2 E , 4 E , 6 E , 8 E ) -Deca-2,4,6,8-tetraenedioic acid mono - {(3 R , 4 S , 5 S , 6 R ) -5-methoxy-4 - [(2 R , 3 R ) -2-methyl-3- (3-methylbut-2-enyl) oxiranyl] -1-oxaspiro [2.5] oct-6-yl} ester ( IUPAC ) ; Fumagillinum ( Latin ) ;
Molecular formula	C 26 H 34 O 7
Brief description	light yellow needles
External identifiers / databases
EC number	245-433-8
ECHA InfoCard	100,041,288
PubChem	6917655
ChemSpider	5292885
DrugBank	DB02640
Wikidata	Q120199
Drug information
ATC code	P01 AX10
properties
Molar mass	458.54 g · mol -1
Physical state	firmly
Melting point	189-194 ° C
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances Caution
H and P phrases	H: 302
	P: no P-phrases
Toxicological data	2000 mg kg −1 ( LD 50 , mouse , oral ) ; 800 mg kg −1 ( LD 50 , mouse , sc ) ;
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Fumagillin is a complex biomolecule.

Occurrence

Aspergillus fumigatus

It occurs naturally in Aspergillus fumigatus and Penicillium nigricans .

application

It is approved in various forms in North America and is used for microsporidiosis . Topical application can be used for microsporidial keratoconjunctivitis . At Nosemose , it is mixed in sugar syrup.

Effects against malaria , amoebas , leishmanias and trypanosomes as well as against neovascularization have been proven and are currently being researched.

effectiveness

Fumagillin binds irreversibly via the spiroepoxide to a histidine group of methionine aminopeptidases (MetAP), which shorten newly synthesized proteins by the N -terminal methionine group corresponding to the start codon . Since this step is essential for the biosynthesis of functional proteins, organisms with only one subtype die of MetAP. For this reason, MetAP inhibitors and thus also fumagillin and its derivatives are being researched as potential antibiotics, among other things. It has also been observed that fumagillin inhibits angioneogenesis in humans, who have two MetAP subtypes, which has led to research into fumagillin and its derivatives as drugs in cancer therapy.

Side effects

Since weight loss has been observed, derivatives are being researched. In clinical studies it has been shown that fumagillin is unsuitable as a drug for cancer therapy due to its high neurotoxicity, which has led to the development of numerous synthetic and semi-synthetic derivatives.

additional

If the acidic side chain is split off from fumagillin, the result is the alcohol fumagillol , which has an immunosuppressive effect.

Trade names

Amebacillin, Fumagilin, Fumidil B

literature

Antiparasitic activities of novel, orally available fumagillin analogs . In: Bioorganic & Medicinal Chemistry Letters 19 (2009) 5128-5131 (PDF; 399 kB; English)
Apiculture Factsheet: Nosema , March 2012 (PDF; 113 kB; English)
Fumagillin and Fumarranol Interact with P. falciparum Methionine Aminopeptidase 2 and Inhibit Malaria Parasite Growth In Vitro and In Vivo . In: Chemistry & Biology, Volume 16, Issue 2, 193-202, February 27, 2009 doi: 10.1016 / j.chembiol.2009.01.006

Web links

Fumagillin Facts Sheet
Entry to fumagillin in ChemicalBook , accessed on 19 September 2011th
Cytokines & Cells Encyclopedia - COPE: Fumagillin

Individual evidence

↑ ^a ^b ^c ^d ^e ^f ^g Entry on fumagillin. In: Römpp Online . Georg Thieme Verlag, accessed on July 2, 2019.
↑ ^a ^b Data sheet Fumagillin from Aspergillus fumigatus from Sigma-Aldrich , accessed on April 2, 2011 ( PDF ).
↑ ^a ^b Entry on fumagillin in the ChemIDplus database of the United States National Library of Medicine (NLM) .
↑ Ingber, DE; Fujita, T .; Kishmoto, S .; Sudo, K .; Kanamaru, T .; Brem, H .; Folkman, J .; Nature 1990,345,555.
↑ As an example only TNP470: "Ingber, D .; Fujita, T .; Kishimoto, S .; Sudo, K .; Kanamaru, T .; Brem, H .; Folkman, J .; Nature 1990, 348, 555. " and CKD-731: "Han, CK; Ahn SK; Bioorganic & Medicinal Chemistry Letters 2000, 10 (1), 39-43." listed.

[RÖMPP_Online-1] ↑ ^a ^b ^c ^d ^e ^f ^g Entry on fumagillin. In: Römpp Online . Georg Thieme Verlag, accessed on July 2, 2019.

[Sigma-2] Data sheet Fumagillin from Aspergillus fumigatus from Sigma-Aldrich , accessed on April 2, 2011 ( PDF ).

[ChemIDplus-3] Entry on fumagillin in the ChemIDplus database of the United States National Library of Medicine (NLM) .

[4] Ingber, DE; Fujita, T .; Kishmoto, S .; Sudo, K .; Kanamaru, T .; Brem, H .; Folkman, J .; Nature 1990,345,555.

[5] As an example only TNP470: "Ingber, D .; Fujita, T .; Kishimoto, S .; Sudo, K .; Kanamaru, T .; Brem, H .; Folkman, J .; Nature 1990, 348, 555. " and CKD-731: "Han, CK; Ahn SK; Bioorganic & Medicinal Chemistry Letters 2000, 10 (1), 39-43." listed.