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.CO[C@@H]3[C@@H](CC[C@]4(CO4)[C@H]3[C@@]5(C)O[C@@H]5CC=C(C)C)OC(=O)\C=C\C=C\C=C\C=C\C(O)=O

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

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 8504		1.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Microsporidiosis 2 Sources: http://adisinsight.springer.com/drugs/800014399	Curative		Approved 8583	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) Health Status: unhealthy Age Group: 50 years (range: 40–64 years) Sex: M+F 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 Health Status: unhealthy Age Group: < 15 years 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) Health Status: unhealthy Age Group: 50 years (range: 40–64 years) Sex: M+F 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) Health Status: unhealthy Age Group: 50 years (range: 40–64 years) Sex: M+F 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) Health Status: unhealthy Age Group: 50 years (range: 40–64 years) Sex: M+F 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) Health Status: unhealthy Age Group: 50 years (range: 40–64 years) Sex: M+F 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) Health Status: unhealthy Age Group: 50 years (range: 40–64 years) Sex: M+F 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) Health Status: unhealthy Age Group: 50 years (range: 40–64 years) Sex: M+F 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) Health Status: unhealthy Age Group: 50 years (range: 40–64 years) Sex: M+F 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) Health Status: unhealthy Age Group: 50 years (range: 40–64 years) Sex: M+F 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) Health Status: unhealthy Age Group: 50 years (range: 40–64 years) Sex: M+F 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 Health Status: unhealthy Age Group: < 15 years 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 Health Status: unhealthy Age Group: < 15 years Sources: https://pubmed.ncbi.nlm.nih.gov/33128055

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1741

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1932	inhibitor 4027 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
Fumagillin reduces adipose tissue formation in murine models of nutritionally induced obesity.	2010-12	20094042
Fumagillin treatment of hepatocellular carcinoma in rats: an in vivo study of antiangiogenesis.	2005-02-14	15682466
The C. elegans methionine aminopeptidase 2 analog map-2 is required for germ cell proliferation.	2004-10-08	15474045
Small molecule inhibitors of methionine aminopeptidase type 2 (MetAP-2).	2004	15516829
Proteomics-based target identification: bengamides as a new class of methionine aminopeptidase inhibitors.	2003-12-26	14534293

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.

Name

Type

Language

FUMAGILLIN DICYCLOHEXYLAMINE SALT

Preferred Name

English

BICYCLOHEXYLAMMONIUM FUMAGILLIN

Common Name

English

BICYCLOHEXYLAMMONIUM FUMMAGILLIN

Common Name

English

FUMAGILLIN DICYCLOHEXYLAMIN

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