U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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
Structure of FUMAGILLIN

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

Description
Curator's Comment: http://adisinsight.springer.com/drugs/800014399 https://www.ncbi.nlm.nih.gov/pubmed/25751824 https://www.ncbi.nlm.nih.gov/pubmed/22229417

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

1953
193
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
 1.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
Approved
8429
Flisint

Approved Use

Microsporidiosis

Launch Date

2001
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
16 μg/mL
EXPERIMENT
https://www.sciencedirect.com/science/article/pii/0041008X89901737
3 mg/kg single, intra-arterial
dose: 3 mg/kg
route of administration: Intra-arterial
experiment type: SINGLE
co-administered:
FUMAGILLIN plasma
Oncorhynchus mykiss
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
9.9 μg × h/mL
EXPERIMENT
https://www.sciencedirect.com/science/article/pii/0041008X89901737
3 mg/kg single, intra-arterial
dose: 3 mg/kg
route of administration: Intra-arterial
experiment type: SINGLE
co-administered:
FUMAGILLIN plasma
Oncorhynchus mykiss
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
5.4 day
EXPERIMENT
https://www.sciencedirect.com/science/article/pii/0041008X89901737
3 mg/kg single, intra-arterial
dose: 3 mg/kg
route of administration: Intra-arterial
experiment type: SINGLE
co-administered:
FUMAGILLIN plasma
Oncorhynchus mykiss
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
20 mg 3 times / day multiple, oral
Recommended
Dose: 20 mg, 3 times / day
Route: oral
Route: multiple
Dose: 20 mg, 3 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/33128055
unhealthy, 50 years (range: 40–64 years)
n = 166
Health Status: unhealthy
Condition: E. bieneusi intestinal microsporidiosis
Age Group: 50 years (range: 40–64 years)
Sex: M+F
Population Size: 166
Sources:
https://pubmed.ncbi.nlm.nih.gov/33128055
Disc. AE: Thrombocytopenia, Skin rash...
AEs leading to
discontinuation/dose reduction:
Thrombocytopenia (severe, 15.1%)
Skin rash (3 patients)
Neutropenia (4.8%)
Liver failure (serious, 1 patient)
Meningoencephalitis (serious, 1 patient)
Neurological impairment (serious, 3 patients)
Hepatitis (serious, 2 patients)
Anaemia (serious, 4 patients)
Haemorrhagic shock (grade 5, 1 patient)
Sources:
https://pubmed.ncbi.nlm.nih.gov/33128055
20 mg 3 times / day multiple, oral
Recommended
Dose: 20 mg, 3 times / day
Route: oral
Route: multiple
Dose: 20 mg, 3 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/33128055
unhealthy, < 15 years
n = 5
Health Status: unhealthy
Condition: E. bieneusi intestinal microsporidiosis
Age Group: < 15 years
Population Size: 5
Sources:
https://pubmed.ncbi.nlm.nih.gov/33128055
Disc. AE: Anaemia, Alanine aminotransferase increase...
AEs leading to
discontinuation/dose reduction:
Anaemia (severe, 1 patient)
Alanine aminotransferase increase (severe, 1 patient)
Sources:
https://pubmed.ncbi.nlm.nih.gov/33128055
AEs

AEs

AESignificanceDosePopulation
Skin rash 3 patients
Disc. AE
20 mg 3 times / day multiple, oral
Recommended
Dose: 20 mg, 3 times / day
Route: oral
Route: multiple
Dose: 20 mg, 3 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/33128055
unhealthy, 50 years (range: 40–64 years)
n = 166
Health Status: unhealthy
Condition: E. bieneusi intestinal microsporidiosis
Age Group: 50 years (range: 40–64 years)
Sex: M+F
Population Size: 166
Sources:
https://pubmed.ncbi.nlm.nih.gov/33128055
Neutropenia 4.8%
Disc. AE
20 mg 3 times / day multiple, oral
Recommended
Dose: 20 mg, 3 times / day
Route: oral
Route: multiple
Dose: 20 mg, 3 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/33128055
unhealthy, 50 years (range: 40–64 years)
n = 166
Health Status: unhealthy
Condition: E. bieneusi intestinal microsporidiosis
Age Group: 50 years (range: 40–64 years)
Sex: M+F
Population Size: 166
Sources:
https://pubmed.ncbi.nlm.nih.gov/33128055
Haemorrhagic shock grade 5, 1 patient
Disc. AE
20 mg 3 times / day multiple, oral
Recommended
Dose: 20 mg, 3 times / day
Route: oral
Route: multiple
Dose: 20 mg, 3 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/33128055
unhealthy, 50 years (range: 40–64 years)
n = 166
Health Status: unhealthy
Condition: E. bieneusi intestinal microsporidiosis
Age Group: 50 years (range: 40–64 years)
Sex: M+F
Population Size: 166
Sources:
https://pubmed.ncbi.nlm.nih.gov/33128055
Liver failure serious, 1 patient
Disc. AE
20 mg 3 times / day multiple, oral
Recommended
Dose: 20 mg, 3 times / day
Route: oral
Route: multiple
Dose: 20 mg, 3 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/33128055
unhealthy, 50 years (range: 40–64 years)
n = 166
Health Status: unhealthy
Condition: E. bieneusi intestinal microsporidiosis
Age Group: 50 years (range: 40–64 years)
Sex: M+F
Population Size: 166
Sources:
https://pubmed.ncbi.nlm.nih.gov/33128055
Meningoencephalitis serious, 1 patient
Disc. AE
20 mg 3 times / day multiple, oral
Recommended
Dose: 20 mg, 3 times / day
Route: oral
Route: multiple
Dose: 20 mg, 3 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/33128055
unhealthy, 50 years (range: 40–64 years)
n = 166
Health Status: unhealthy
Condition: E. bieneusi intestinal microsporidiosis
Age Group: 50 years (range: 40–64 years)
Sex: M+F
Population Size: 166
Sources:
https://pubmed.ncbi.nlm.nih.gov/33128055
Hepatitis serious, 2 patients
Disc. AE
20 mg 3 times / day multiple, oral
Recommended
Dose: 20 mg, 3 times / day
Route: oral
Route: multiple
Dose: 20 mg, 3 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/33128055
unhealthy, 50 years (range: 40–64 years)
n = 166
Health Status: unhealthy
Condition: E. bieneusi intestinal microsporidiosis
Age Group: 50 years (range: 40–64 years)
Sex: M+F
Population Size: 166
Sources:
https://pubmed.ncbi.nlm.nih.gov/33128055
Neurological impairment serious, 3 patients
Disc. AE
20 mg 3 times / day multiple, oral
Recommended
Dose: 20 mg, 3 times / day
Route: oral
Route: multiple
Dose: 20 mg, 3 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/33128055
unhealthy, 50 years (range: 40–64 years)
n = 166
Health Status: unhealthy
Condition: E. bieneusi intestinal microsporidiosis
Age Group: 50 years (range: 40–64 years)
Sex: M+F
Population Size: 166
Sources:
https://pubmed.ncbi.nlm.nih.gov/33128055
Anaemia serious, 4 patients
Disc. AE
20 mg 3 times / day multiple, oral
Recommended
Dose: 20 mg, 3 times / day
Route: oral
Route: multiple
Dose: 20 mg, 3 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/33128055
unhealthy, 50 years (range: 40–64 years)
n = 166
Health Status: unhealthy
Condition: E. bieneusi intestinal microsporidiosis
Age Group: 50 years (range: 40–64 years)
Sex: M+F
Population Size: 166
Sources:
https://pubmed.ncbi.nlm.nih.gov/33128055
Thrombocytopenia severe, 15.1%
Disc. AE
20 mg 3 times / day multiple, oral
Recommended
Dose: 20 mg, 3 times / day
Route: oral
Route: multiple
Dose: 20 mg, 3 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/33128055
unhealthy, 50 years (range: 40–64 years)
n = 166
Health Status: unhealthy
Condition: E. bieneusi intestinal microsporidiosis
Age Group: 50 years (range: 40–64 years)
Sex: M+F
Population Size: 166
Sources:
https://pubmed.ncbi.nlm.nih.gov/33128055
Alanine aminotransferase increase severe, 1 patient
Disc. AE
20 mg 3 times / day multiple, oral
Recommended
Dose: 20 mg, 3 times / day
Route: oral
Route: multiple
Dose: 20 mg, 3 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/33128055
unhealthy, < 15 years
n = 5
Health Status: unhealthy
Condition: E. bieneusi intestinal microsporidiosis
Age Group: < 15 years
Population Size: 5
Sources:
https://pubmed.ncbi.nlm.nih.gov/33128055
Anaemia severe, 1 patient
Disc. AE
20 mg 3 times / day multiple, oral
Recommended
Dose: 20 mg, 3 times / day
Route: oral
Route: multiple
Dose: 20 mg, 3 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/33128055
unhealthy, < 15 years
n = 5
Health Status: unhealthy
Condition: E. bieneusi intestinal microsporidiosis
Age Group: < 15 years
Population Size: 5
Sources:
https://pubmed.ncbi.nlm.nih.gov/33128055
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer
P-gp
1461
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
P-gp
1650
 yes
Sourcing

Sourcing

Vendor/AggregatorIDURL
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
PubMed

PubMed

TitleDatePubMed
Small molecule inhibitors of methionine aminopeptidase type 2 (MetAP-2).
2004
The C. elegans methionine aminopeptidase 2 analog map-2 is required for germ cell proliferation.
2004 Oct 8
Patents

Patents

JP3923798B2
2
JPH02223525A
2

Sample Use Guides

In Vivo Use Guide
Curator's Comment: can also be used topically as eye drops
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
Created
by admin
on Sat Dec 16 16:48:29 GMT 2023
Edited
by admin
on Sat Dec 16 16:48:29 GMT 2023
Record UNII
7OW73204U1
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
FUMAGILLIN
INN   MART.   MI   WHO-DD  
INN  
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
2,4,6,8-DECATETRAENEDIOIC ACID, 1-((3R,4S,5S,6R)-5-METHOXY-4-((2R,3R)-2-METHYL-3-(3-METHYL-2-BUTEN-1-YL)-2-OXIRANYL)-1-OXASPIRO(2.5)OCT-6-YL) ESTER, (2E,4E,6E,8E)-
Systematic Name English
AMEBACILIN
Common Name English
(-)-FUMAGILLIN
Common Name English
ZGN-201
Code English
FUMIDIL
Brand Name English
2,4,6,8-DECATETRAENEDIOIC ACID, 4-(1,2-EPOXY-1,5-DIMETHYL-4-HEXENYL)-5-METHOXY-1-OXASPIRO(2,5)OCT-6-YL ESTER
Systematic Name English
2,4,6,8-DECATETRAENEDIOIC ACID, MONO((3R,4S,5S,6R)-5-METHOXY-4-((2R,3R)-2-METHYL-3-(3-METHYL-2-BUTENYL)OXIRANYL)-1-OXASPIRO(2.5)OCT-6-YL) ESTER, (2E,4E,6E,8E)-
Systematic Name English
FUMAGILLIN [MART.]
Common Name English
FUMAGILLIN [MI]
Common Name English
NSC-9168
Code English
Classification Tree Code System Code
WHO-ATC P01AX10
Created by admin on Sat Dec 16 16:48:29 GMT 2023 , Edited by admin on Sat Dec 16 16:48:29 GMT 2023
NCI_THESAURUS C259
Created by admin on Sat Dec 16 16:48:30 GMT 2023 , Edited by admin on Sat Dec 16 16:48:30 GMT 2023
WHO-VATC QP51AX23
Created by admin on Sat Dec 16 16:48:30 GMT 2023 , Edited by admin on Sat Dec 16 16:48:30 GMT 2023
EU-Orphan Drug EU/3/01/081
Created by admin on Sat Dec 16 16:48:30 GMT 2023 , Edited by admin on Sat Dec 16 16:48:30 GMT 2023
Code System Code Type Description
MESH
C026211
Created by admin on Sat Dec 16 16:48:30 GMT 2023 , Edited by admin on Sat Dec 16 16:48:30 GMT 2023
PRIMARY
MERCK INDEX
m5585
Created by admin on Sat Dec 16 16:48:30 GMT 2023 , Edited by admin on Sat Dec 16 16:48:30 GMT 2023
PRIMARY Merck Index
EPA CompTox
DTXSID7040736
Created by admin on Sat Dec 16 16:48:30 GMT 2023 , Edited by admin on Sat Dec 16 16:48:30 GMT 2023
PRIMARY
ECHA (EC/EINECS)
245-433-8
Created by admin on Sat Dec 16 16:48:30 GMT 2023 , Edited by admin on Sat Dec 16 16:48:30 GMT 2023
PRIMARY
SMS_ID
100000087379
Created by admin on Sat Dec 16 16:48:30 GMT 2023 , Edited by admin on Sat Dec 16 16:48:30 GMT 2023
PRIMARY
RXCUI
1926480
Created by admin on Sat Dec 16 16:48:30 GMT 2023 , Edited by admin on Sat Dec 16 16:48:30 GMT 2023
PRIMARY
CHEBI
42601
Created by admin on Sat Dec 16 16:48:30 GMT 2023 , Edited by admin on Sat Dec 16 16:48:30 GMT 2023
PRIMARY
DAILYMED
7OW73204U1
Created by admin on Sat Dec 16 16:48:30 GMT 2023 , Edited by admin on Sat Dec 16 16:48:30 GMT 2023
PRIMARY
NSC
9168
Created by admin on Sat Dec 16 16:48:30 GMT 2023 , Edited by admin on Sat Dec 16 16:48:30 GMT 2023
PRIMARY
FDA UNII
7OW73204U1
Created by admin on Sat Dec 16 16:48:30 GMT 2023 , Edited by admin on Sat Dec 16 16:48:30 GMT 2023
PRIMARY
INN
225
Created by admin on Sat Dec 16 16:48:30 GMT 2023 , Edited by admin on Sat Dec 16 16:48:30 GMT 2023
PRIMARY
ChEMBL
CHEMBL32838
Created by admin on Sat Dec 16 16:48:30 GMT 2023 , Edited by admin on Sat Dec 16 16:48:30 GMT 2023
PRIMARY
CAS
23110-15-8
Created by admin on Sat Dec 16 16:48:29 GMT 2023 , Edited by admin on Sat Dec 16 16:48:29 GMT 2023
PRIMARY
CHEBI
48635
Created by admin on Sat Dec 16 16:48:30 GMT 2023 , Edited by admin on Sat Dec 16 16:48:30 GMT 2023
PRIMARY
PUBCHEM
6917655
Created by admin on Sat Dec 16 16:48:30 GMT 2023 , Edited by admin on Sat Dec 16 16:48:30 GMT 2023
PRIMARY
DRUG BANK
DB02640
Created by admin on Sat Dec 16 16:48:30 GMT 2023 , Edited by admin on Sat Dec 16 16:48:30 GMT 2023
PRIMARY
NCI_THESAURUS
C75963
Created by admin on Sat Dec 16 16:48:30 GMT 2023 , Edited by admin on Sat Dec 16 16:48:30 GMT 2023
PRIMARY
EVMPD
SUB23269
Created by admin on Sat Dec 16 16:48:29 GMT 2023 , Edited by admin on Sat Dec 16 16:48:29 GMT 2023
PRIMARY
DRUG CENTRAL
3253
Created by admin on Sat Dec 16 16:48:30 GMT 2023 , Edited by admin on Sat Dec 16 16:48:30 GMT 2023
PRIMARY
WIKIPEDIA
FUMAGILLIN
Created by admin on Sat Dec 16 16:48:30 GMT 2023 , Edited by admin on Sat Dec 16 16:48:30 GMT 2023
PRIMARY
Related Record Type Details
Structure of BICYCLOHEXYLAMMONIUM FUMAGILLIN
SALT/SOLVATE -> PARENT
Related Record Type Details
Structure of FUMAGILLIN
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