ETOMOXIR

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C17H23ClO4
Molecular Weight	326.815
Optical Activity	( + )
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCOC(=O)[C@@]2(CCCCCCOC1=CC=C(Cl)C=C1)CO2

InChI

InChIKey=DZLOHEOHWICNIL-QGZVFWFLSA-N

InChI=1S/C17H23ClO4/c1-2-20-16(19)17(13-22-17)11-5-3-4-6-12-21-15-9-7-14(18)8-10-15/h7-10H,2-6,11-13H2,1H3/t17-/m1/s1

HIDE SMILES / InChI

Description
Sources: http://adisinsight.springer.com/drugs/800000032 | https://www.ncbi.nlm.nih.gov/pubmed/17319797 | https://www.ncbi.nlm.nih.gov/pubmed/1577399 | https://www.ncbi.nlm.nih.gov/pubmed/1930298 | https://www.ncbi.nlm.nih.gov/pubmed/1930297

Etomoxir is an irreversible inhibitor of carnitine O-palmitoyltransferase (CPT) I. It inhibits fatty acid oxidation and fatty acid and cholesterol synthesis in an enantiomer-selective manner: only the R-enantiomer of etomoxir inhibits fatty acid oxidation, S-enantiomer inhibits fatty acid and cholesterol synthesis but not fatty acid oxidation. Etomoxir was studied for the treatment of congestive heart failure and type II diabetes, however, its development was discontinued.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Carnitine O-palmitoyltransferase 1, liver isoform 15 Target ID: CHEMBL1293194 Sources: http://adisinsight.springer.com/drugs/800000032 \| https://www.ncbi.nlm.nih.gov/pubmed/19138173 \| https://www.ncbi.nlm.nih.gov/pubmed/7929365 \| https://www.ncbi.nlm.nih.gov/pubmed/21348853 \| https://www.ncbi.nlm.nih.gov/pubmed/3197271	Inhibitor 8297
Carnitine O-palmitoyltransferase 1, muscle isoform 15 Target ID: CHEMBL2216739 Sources: http://adisinsight.springer.com/drugs/800000032 \| https://www.ncbi.nlm.nih.gov/pubmed/19138173 \| https://www.ncbi.nlm.nih.gov/pubmed/7929365 \| https://www.ncbi.nlm.nih.gov/pubmed/3197271	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Congestive heart failure 54 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17319797 https://www.ncbi.nlm.nih.gov/pubmed/10887055	Primary		Phase II 1132	Unknown Approved Use Unknown
Type 2 diabetes mellitus 259 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1577399 https://www.ncbi.nlm.nih.gov/pubmed/1943747	Primary		Phase II 1132	Unknown Approved Use Unknown

Doses

Dose	Population	Adverse events
80 mg 1 times / day multiple, oral Highest studied dose Dose: 80 mg, 1 times / day Route: oral Route: multiple Dose: 80 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17319797 Page: p.210	unhealthy, ADULT n = 108 Health Status: unhealthy Condition: congestive heart failure Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 108 Sources: https://pubmed.ncbi.nlm.nih.gov/17319797 Page: p.210	Disc. AE: Transaminases increased, Arrhythmia... AEs leading to discontinuation/dose reduction: Transaminases increased (Moderate, 0.9%) Arrhythmia (Moderate, 0.9%) Elevated liver enzyme levels (Moderate, 2.8%) Sources: https://pubmed.ncbi.nlm.nih.gov/17319797 Page: p.210

AEs

AE	Significance	Dose	Population
Arrhythmia	Moderate, 0.9% Disc. AE	80 mg 1 times / day multiple, oral Highest studied dose Dose: 80 mg, 1 times / day Route: oral Route: multiple Dose: 80 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17319797 Page: p.210	unhealthy, ADULT n = 108 Health Status: unhealthy Condition: congestive heart failure Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 108 Sources: https://pubmed.ncbi.nlm.nih.gov/17319797 Page: p.210
Transaminases increased	Moderate, 0.9% Disc. AE	80 mg 1 times / day multiple, oral Highest studied dose Dose: 80 mg, 1 times / day Route: oral Route: multiple Dose: 80 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17319797 Page: p.210	unhealthy, ADULT n = 108 Health Status: unhealthy Condition: congestive heart failure Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 108 Sources: https://pubmed.ncbi.nlm.nih.gov/17319797 Page: p.210
Elevated liver enzyme levels	Moderate, 2.8% Disc. AE	80 mg 1 times / day multiple, oral Highest studied dose Dose: 80 mg, 1 times / day Route: oral Route: multiple Dose: 80 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17319797 Page: p.210	unhealthy, ADULT n = 108 Health Status: unhealthy Condition: congestive heart failure Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 108 Sources: https://pubmed.ncbi.nlm.nih.gov/17319797 Page: p.210

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P0056G9	https://www.1pchem.com/search?query=1P0056G9
1PlusChem LLC	1P009CSA	https://www.1pchem.com/search?query=1P009CSA
AChemBlock	R16055	http://www.achemblock.com/catalogsearch/result/?q=R16055
AK Scientific	3994AH	https://aksci.com/item_detail.php?cat=3994AH
AKOS	AKOS028109213	http://akoscompounds.de/catalogue/AKosSamplesiSSretrieval.php?GUID=4e4caa52-3dca-4da0-b75a-caeae59e1096&IDNUMBERS=AKOS028109213
Alfa Chemistry	ACM82258364	http://www.alfa-chemistry.com/search.aspx?q=ACM82258364
Angene	AGN-PC-0JL44X	http://www.angenechemical.com/productshow/AGN-PC-0JL44X.html
BLD Pharm	BD129873	http://www.bldpharm.com/search/Search.html?keyword=BD129873
BLD Pharm	BD630045	http://www.bldpharm.com/search/Search.html?keyword=BD630045
Chem Scene	CS-0325	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0325
KeyOrganics	AS-56541	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-56541
Lab Network	LN01297928	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01297928
MedChem Express	HY-50202	https://www.medchemexpress.com/search.html?q=HY-50202&ft=&fa=&fp=
MolPort	MolPort-003-847-333	https://www.molport.com/shop/molecule-link/MolPort-003-847-333
Molnova	M10974	https://www.molnova.com/en/serch-list.html?keywords=M10974
MuseChem	R002599	https://www.musechem.com/product/R002599.html
ShangHai Biochempartner	BCP07911	http://www.biochempartner.com/search_BCP07911
Toronto Research Chemicals	C181272	https://www.trc-canada.com/product-detail/?CatNum=C181272
Toronto Research Chemicals	E933500	https://www.trc-canada.com/product-detail/?CatNum=E933500
Toronto Research Chemicals	E933505	https://www.trc-canada.com/product-detail/?CatNum=E933505
Toronto Research Chemicals	M539400	https://www.trc-canada.com/product-detail/?CatNum=M539400
Wonderchem	WD04YW1	http://www.wonder-chem.com/search.html?text=WD04YW1
eMolecules	31592713	https://orderbb.emolecules.com/search/#?query=31592713
eMolecules	31592719	https://orderbb.emolecules.com/search/#?query=31592719
mcule	MCULE-6112820032	https://mcule.com/MCULE-6112820032/
mcule	MCULE-6482996940	https://mcule.com/MCULE-6482996940/

PubMed

Title	Date	PubMed
Interactions of inhibitors of carnitine palmitoyltransferase I and fibrates in cultured hepatocytes.	1988 Jul 1	3421940
The use of partial fatty acid oxidation inhibitors for metabolic therapy of angina pectoris and heart failure.	2002 Nov	12439634
Plasma free fatty acids and peroxisome proliferator-activated receptor alpha in the control of myocardial uncoupling protein levels.	2005 Dec	16306367
Characterization of hepatic mitochondrial injury induced by fatty acid oxidation inhibitors.	2009 Jan	19234235
Stimulation of lipogenesis as well as fatty acid oxidation protects against palmitate-induced INS-1 beta-cell death.	2011 Mar	21209018
Apoptotic efficacy of etomoxir in human acute myeloid leukemia cells. Cooperation with arsenic trioxide and glycolytic inhibitors, and regulation by oxidative stress and protein kinase activities.	2014	25506699

Sample Use Guides

In Vivo Use Guide

The ERGO (etomoxir for the recovery of glucose oxidation) study was designed in which etomoxir was tested at a dose of 80 and 40 mg compared with placebo for a period of 6 months in patients with CHF (congestive heart failure).

Route of Administration: Oral

In Vitro Use Guide

The apoptotic and chemo-sensitizing action of the fatty acid oxidation inhibitor etomoxir was analyzed in human acute myeloid leukemia cells. Etomoxir caused negligible lethality at concentrations up to 100 µM, but efficaciously cooperated to cause apoptosis with the anti-leukemic agent arsenic trioxide (ATO, Trisenox), and with lower efficacy with other anti-tumour drugs (etoposide, cisplatin), in HL60 cells. Etomoxir-ATO cooperation was also observed in NB4 human acute promyelocytic cells, but not in normal (non-tumour) mitogen-stimulated human peripheral blood lymphocytes. Biochemical determinations in HL60 cells indicated that etomoxir (25-200 µM) dose-dependently inhibited mitochondrial respiration while slightly stimulating glycolysis, and only caused marginal alterations in total ATP content and adenine nucleotide pool distribution.

Name

Type

Language

ETOMOXIR

Official Name

English

(R)-ETHYL 2-(6-(4-CHLOROPHENOXY)HEXYL)OXIRANE-2-CARBOXYLATE

Systematic Name

English

2-OXIRANECARBOXYLIC ACID, 2-(6-(4-CHLOROPHENOXY)HEXYL)-, ETHYL ESTER, (2R)-

Systematic Name

English

etomoxir [INN]

Common Name

English

Etomoxir [WHO-DD]

Common Name

English

ETHYL (+)-(R)-2-(6-(P-CHLOROPHENOXY)HEXYL)GLYCIDATE

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C471