BICYCLOHEXYLAMMONIUM FUMAGILLIN

First approved in 1953

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C26H34O7.C12H23N
Molecular Weight	639.8617
Optical Activity	UNSPECIFIED
Defined Stereocenters	6 / 6
E/Z Centers	4
Charge	0

SHOW SMILES / InChI

Structure of BICYCLOHEXYLAMMONIUM FUMAGILLIN

Structure Search

SMILES

C1CCC(CC1)NC2CCCCC2.[H][C@@]3([C@H](OC)[C@@H](CC[C@]34CO4)OC(=O)\C=C\C=C\C=C\C=C\C(O)=O)[C@@]5(C)O[C@@H]5CC=C(C)C

InChI

InChIKey=OLRILZDTQKZQIG-PNLOCOOESA-N

InChI=1S/C26H34O7.C12H23N/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;1-3-7-11(8-4-1)13-12-9-5-2-6-10-12/h5-13,19-20,23-24H,14-17H2,1-4H3,(H,27,28);11-13H,1-10H2/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

Molecular Formula	C12H23N
Molecular Weight	181.3177
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.has-sante.fr/portail/upload/docs/application/pdf/ct032497.pdf
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

Targets

Primary Target	Pharmacology	Condition	Potency
Methionine aminopeptidase 2 4 Target ID: CHEMBL3922 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26369821	Inhibitor 8297		1.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Microsporidiosis 2 Sources: http://adisinsight.springer.com/drugs/800014399	Curative		Approved 8429	Flisint Approved Use Microsporidiosis Launch Date 2001

C_max

Value	Dose	Co-administered	Analyte	Population
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

Value	Dose	Co-administered	Analyte	Population
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

T_1/2

Value	Dose	Co-administered	Analyte	Population
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

Dose	Population	Adverse 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

AE	Significance	Dose	Population
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

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/28739698/	yes

Sourcing

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

PubMed

Title	Date	PubMed
Proteomics-based target identification: bengamides as a new class of methionine aminopeptidase inhibitors.	2003 Dec 26	14534293
Small molecule inhibitors of methionine aminopeptidase type 2 (MetAP-2).	2004	15516829
The C. elegans methionine aminopeptidase 2 analog map-2 is required for germ cell proliferation.	2004 Oct 8	15474045
Fumagillin treatment of hepatocellular carcinoma in rats: an in vivo study of antiangiogenesis.	2005 Feb 14	15682466
Fumagillin reduces adipose tissue formation in murine models of nutritionally induced obesity.	2010 Dec	20094042

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 Created by `admin` on `Fri Dec 15 16:10:20 GMT 2023` Edited by `admin` on `Fri Dec 15 16:10:20 GMT 2023`
Record UNII	0W72P6E6EY
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

BICYCLOHEXYLAMMONIUM FUMAGILLIN

Common Name

English

BICYCLOHEXYLAMMONIUM FUMMAGILLIN

Common Name

English

FUMAGILLIN DICYCLOHEXYLAMIN

Common Name

English

FUMAGILLIN DICYCLOHEXYLAMINE SALT

Common Name

English

BICYCLOHEXYLAMMONIUM FUMAGILLIN [GREEN BOOK]

Common Name

English

FUMAGILLIN DICYCLOHEXYLAMINE

Common Name

English

FUMAGILLIN DICYCLOHEXYLAMINE SALT [MI]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C258