FRCD

Common Name	Fumagillin(F05004)
2D Structure
Description	Fumagillin 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. (L1966, A3058)
FRCD ID	F05004
CAS Number	23110-15-8
PubChem CID	6436022
Formula	C26H34O7
IUPAC Name	(2E,4E,6E,8E)-10-[[(3R,4S,5S,6R)-5-methoxy-4-[2-methyl-3-(3-methylbut-2-enyl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-yl]oxy]-10-oxodeca-2,4,6,8-tetraenoic acid
InChI Key	NGGMYCMLYOUNGM-HTYDLQADSA-N
InChI	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
Canonical SMILES	CC(=CCC1C(O1)(C)C2C(C(CCC23CO3)OC(=O)C=CC=CC=CC=CC(=O)O)OC)C
Isomeric SMILES	CC(=CCC1C(O1)(C)[C@H]2[C@@H]([C@@H](CC[C@]23CO3)OC(=O)/C=C/C=C/C=C/C=C/C(=O)O)OC)C
Wikipedia	Fumagillin
Synonyms	Fumagillin DCH fumagillin Amebacillin Fugilin Fugillin Fumidil Fumagillina [DCIT] Fumagilina [INN-Spanish] Fumagilline [INN-French] Fumagillinum [INN-Latin]
Classifies	Fungal Toxin
Update Date	Nov 13, 2018 17:07

Kingdom	Organic compounds
Superclass	Lipids and lipid-like molecules
Class	Fatty Acyls
Subclass	Fatty acids and conjugates
Intermediate Tree Nodes	Not available
Direct Parent	Medium-chain fatty acids
Alternative Parents	Hydrocarbon derivatives Organic oxides Dicarboxylic acids and derivatives Carbonyl compounds Dialkyl ethers Oxacyclic compounds Carboxylic acids Unsaturated fatty acids Epoxides Enoate esters Fatty acid esters Epoxy fatty acids Branched fatty acids
Molecular Framework	Aliphatic heteropolycyclic compounds
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
Description	This compound 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.

Property Name	Property Value
Molecular Weight	458.551
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	11
Complexity	879
Monoisotopic Mass	458.23
Exact Mass	458.23
XLogP	4
Formal Charge	0
Heavy Atom Count	33
Defined Atom Stereocenter Count	4
Undefined Atom Stereocenter Count	2
Defined Bond Stereocenter Count	4
Undefined Bond Stereocenter Count	0
Isotope Atom Count	0
Covalently-Bonded Unit Count	1

Model	Result	Probability
Absorption
Blood-Brain Barrier	BBB+	0.5248
Human Intestinal Absorption	HIA+	0.8342
Caco-2 Permeability	Caco2-	0.5139
P-glycoprotein Substrate	Substrate	0.6893
P-glycoprotein Inhibitor	Inhibitor	0.6251
P-glycoprotein Inhibitor	Inhibitor	0.8337
Renal Organic Cation Transporter	Non-inhibitor	0.8420
Distribution
Subcellular localization	Mitochondria	0.8792
Metabolism
CYP450 2C9 Substrate	Non-substrate	0.8591
CYP450 2D6 Substrate	Non-substrate	0.8809
CYP450 3A4 Substrate	Substrate	0.6803
CYP450 1A2 Inhibitor	Non-inhibitor	0.8653
CYP450 2C9 Inhibitor	Non-inhibitor	0.8154
CYP450 2D6 Inhibitor	Non-inhibitor	0.9412
CYP450 2C19 Inhibitor	Non-inhibitor	0.8814
CYP450 3A4 Inhibitor	Non-inhibitor	0.8680
CYP Inhibitory Promiscuity	Low CYP Inhibitory Promiscuity	0.9559
Excretion
Toxicity
Human Ether-a-go-go-Related Gene Inhibition	Weak inhibitor	0.9768
Human Ether-a-go-go-Related Gene Inhibition	Non-inhibitor	0.8463
AMES Toxicity	AMES toxic	0.5360
Carcinogens	Non-carcinogens	0.8927
Fish Toxicity	High FHMT	0.7702
Tetrahymena Pyriformis Toxicity	High TPT	0.9977
Honey Bee Toxicity	High HBT	0.8319
Biodegradation	Not ready biodegradable	0.8665
Acute Oral Toxicity	III	0.5237
Carcinogenicity (Three-class)	Non-required	0.5994

Model	Value	Unit
Absorption
Aqueous solubility	-3.6957	LogS
Caco-2 Permeability	0.8999	LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity	2.9093	LD50, mol/kg
Fish Toxicity	0.6083	pLC50, mg/L
Tetrahymena Pyriformis Toxicity	1.0949	pIGC50, ug/L

Title	Journal	Date	Pubmed ID
Toward a Cancer Drug of Fungal Origin.	Med Res Rev	2015 Sep	25850821
Review on Mycotoxin Issues in Ruminants: Occurrence in Forages, Effects of Mycotoxin Ingestion on Health Status and Animal Performance and Practical Strategies to Counteract Their Negative Effects.	Toxins (Basel)	2015 Aug 12	26274974
Microsporidiosis: epidemiology, clinical data and therapy.	Gastroenterol Clin Biol	2010 Sep	20702053
Therapeutic strategies for human microsporidia infections.	Expert Rev Anti Infect Ther	2005 Jun	15954858
Microsporidiosis: an emerging and opportunistic infection in humans and animals.	Acta Trop	2005 Apr	15777637
Epidemiology of microsporidiosis: sources and modes of transmission.	Vet Parasitol	2004 Dec 9	15567583
Toxicity and pharmacokinetics of the antibiotic fumagillin in yearling rainbow trout (Salmo gairdneri).	Toxicol Appl Pharmacol	1989 May	2718173
Mycoflora and mycotoxins of peanut (Arachis hypogaea L.) seeds in Egypt. III. Cellulose-decomposing and mycotoxin-producing fungi.	Mycopathologia	1988 Oct	3216881

Targets

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
Mechanism of Action:: Fumagillin 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.

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 ]