FUMAGILLIN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C26H34O7
Molecular Weight	458.544
Optical Activity	UNSPECIFIED
Defined Stereocenters	6 / 6
E/Z Centers	4
Charge	0

SHOW SMILES / InChI

SMILES

[H][C@@]1([C@H](OC)[C@@H](CC[C@]12CO2)OC(=O)\C=C\C=C\C=C\C=C\C(O)=O)[C@@]3(C)O[C@@H]3CC=C(C)C

InChI

InChIKey=NGGMYCMLYOUNGM-CSDLUJIJSA-N

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

HIDE SMILES / InChI

Molecular Formula	C26H34O7
Molecular Weight	458.544
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	5 / 6
E/Z Centers	4
Optical Activity	UNSPECIFIED

Description

Fumagillin, an antimicrobial compound first isolated in 1949 from the fungus Aspergillus fumigatusa, naturally occurring water-insoluble antibacterial agent developed by sanofi-aventis, is approved in France for the treatment of microsporidiosis. Fumagillin (Flisint, Sanofi-Aventis, Paris, France) has been approved in France since 2002 for the treatment of intestinal microsporidiosis due to E. bieneusi in patients with AIDS, and is also available through an expanded access program for patients without AIDS. It has not been approved, however, by the US Food and Drug Administration. The discovery of fumagillin, a MetAP-2 inhibitor, with potent antiangiogenic and antiproliferative activities promoted the development of fumagillin analogues as a novel class of anticancer agents. It has been the subject of research in cancer treatments by employing its angiogenesis inhibitory properties.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Methionine aminopeptidase 2 4	Inhibitor 8,297		1.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Microsporidiosis 2	Curative		Approved 8,429	Flisint

C_max

Value	Dose	Co-administered	Analyte	Population
16 μg/mL	3 mg/kg single, intra-arterial		FUMAGILLIN plasma	Oncorhynchus mykiss

AUC

Value	Dose	Co-administered	Analyte	Population
9.9 μg × h/mL	3 mg/kg single, intra-arterial		FUMAGILLIN plasma	Oncorhynchus mykiss

T_1/2

Value	Dose	Co-administered	Analyte	Population
5.4 day	3 mg/kg single, intra-arterial		FUMAGILLIN plasma	Oncorhynchus mykiss

Doses

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Dose	Population	Adverse events
20 mg 3 times / day multiple, oral Recommended	unhealthy, 50 years (range: 40–64 years) n = 166	Disc. AE: Thrombocytopenia, Skin rash...
20 mg 3 times / day multiple, oral Recommended	unhealthy, < 15 years n = 5	Disc. AE: Anaemia, Alanine aminotransferase increase...

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AEs

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AE	Significance	Dose	Population
Skin rash	3 patients Disc. AE	20 mg 3 times / day multiple, oral Recommended	unhealthy, 50 years (range: 40–64 years) n = 166
Neutropenia	4.8% Disc. AE	20 mg 3 times / day multiple, oral Recommended	unhealthy, 50 years (range: 40–64 years) n = 166
Haemorrhagic shock	grade 5, 1 patient Disc. AE	20 mg 3 times / day multiple, oral Recommended	unhealthy, 50 years (range: 40–64 years) n = 166
Liver failure	serious, 1 patient Disc. AE	20 mg 3 times / day multiple, oral Recommended	unhealthy, 50 years (range: 40–64 years) n = 166
Meningoencephalitis	serious, 1 patient Disc. AE	20 mg 3 times / day multiple, oral Recommended	unhealthy, 50 years (range: 40–64 years) n = 166

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1,461

Drug as perpetrator

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Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1,650	inhibitor 3,277	yes

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Sourcing

Sourcing

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Vendor/Aggregator	ID	URL
ChEBI	CHEBI:48635	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:48635
MolPort	MolPort-023-276-199	https://www.molport.com/shop/molecule-link/MolPort-023-276-199
ZINC	ZINC000004098264	http://zinc15.docking.org/substances/ZINC000004098264

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PubMed

Title	Date	PubMed
No data available in table

Patents

Sample Use Guides

In Vivo Use Guide

20 mg orally three times per day for 14 days

Route of Administration: Oral

In Vitro Use Guide

During in vitro differentiation of murine 3T3-F442A preadipocytes, administration of fumagillin (>/=1 uM) resulted in reduced expression of methionine aminopeptidase-2, and in enhanced differentiation rate.

Substance Class	Chemical
Record UNII	7OW73204U1
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

FUMAGILLIN

Official Name

English

2,4,6,8-DECATETRAENEDIOIC ACID, MONO(5-METHOXY-4-(2-METHYL-3-(3-METHYL-2-BUTENYL)OXIRANYL)-1-OXASPIRO(2.5)OCT-6-YL) ESTER, (3R- (3.ALPHA.,4.ALPHA.(2R*,3R*),5.BETA.,6.BETA.(2E,4E,6E,8E)))-

Systematic Name

English

Fumagillin [WHO-DD]

Common Name

English

fumagillin [INN]

Common Name

English

2,4,6,8-DECATETRAENEDIOIC ACID, MONO(4-(1,2-EPOXY-1,5-DIMETHYL-4-HEXENYL)-5-METHOXY-1-OXASPIRO(2.5)OCT-6-YL) ESTER

Systematic Name

English

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Classification Tree

Code System

Code

Other agents against amoebiasis and other protozoal diseases

WHO-ATC

P01AX10

Antineoplastic Agent

NCI_THESAURUS

C259

Other antiprotozoal agents

WHO-VATC

QP51AX23

Withdrawn

EU-Orphan Drug

EU/3/01/081

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Code System

Code

Type

Description

MESH

C026211

PRIMARY

MERCK INDEX

m5585

PRIMARY

Merck Index

EPA CompTox

DTXSID7040736

PRIMARY

ECHA (EC/EINECS)

245-433-8

PRIMARY

SMS_ID

100000087379

PRIMARY

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Related Record

Type

Details


					0W72P6E6EY

BICYCLOHEXYLAMMONIUM FUMAGILLIN

SALT/SOLVATE -> PARENT

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Related Record

Type

Details


					7OW73204U1

FUMAGILLIN

ACTIVE MOIETY

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SMILES

InChI

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2

Drug as perpetrator