ETHIONAMIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C8H10N2S
Molecular Weight	166.243
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCC1=CC(=CC=N1)C(N)=S

InChI

InChIKey=AEOCXXJPGCBFJA-UHFFFAOYSA-N

InChI=1S/C8H10N2S/c1-2-7-5-6(8(9)11)3-4-10-7/h3-5H,2H2,1H3,(H2,9,11)

HIDE SMILES / InChI

Molecular Formula	C8H10N2S
Molecular Weight	166.243
Charge	0
Count

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

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2006/013026s024lbl.pdf
Curator's Comment: Description was created using several sources including: http://www.ncbi.nlm.nih.gov/pubmed/13741471; https://www.ncbi.nlm.nih.gov/pubmed/17220416; http://www.ncbi.nlm.nih.gov/pubmed/26435990

Ethionamide is a second-line agent, structurally similar to isoniazid, used as a second-line therapy for the treatment of multidrug-resistant tuberculosis or active tuberculosis in case of patient intolerance to other drugs. Depending on its the concentration at the infected site and the susceptibility of the infecting organism it may be bacteriostatic or bactericidal. When used alone rapidly develops bacterial resistance. Ethionamide was approved by FDA in 1965 as TRECATOR manufactured by Wyeth Pharmaceuticals Inc. (purchased by Pfizer in 2009). Ethionamide is specific for Mycobacteria and is thought to exert a toxic effect on mycolic acid components of the bacterial cell wall when activated through intermediate S-oxidation by EtaA. Mycolic acid synthesis was shown to be inhibited by ethionamide in the EthA protein-overexpressing mycobacteria,

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Catalase-peroxidase 3 Target ID: P9WIE5\|\|\|Q50553 Gene ID: 885638.0 Gene Symbol: katG Target Organism: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) Sources: http://www.drugbank.ca/drugs/DB00609	Substrate 661
Enoyl-[acyl-carrier-protein] reductase 5 Target ID: CHEMBL1849 Sources: http://www.ncbi.nlm.nih.gov/pubmed/10944230	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Tuberculosis 83 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2006/013026s024lbl.pdf	Curative		Approved 8583	TRECATOR Approved Use Trecator is primarily indicated for the treatment of active tuberculosis in patients with M. tuberculosis resistant to isoniazid or rifampin, or when there is intolerance on the part of the patient to other drugs. Its use alone in the treatment of tuberculosis results in the rapid development of resistance. It is essential, therefore, to give a suitable companion drug or drugs, the choice being based on the results of susceptibility tests. If the susceptibility tests indicate that the patient's organism is resistant to one of the first-line antituberculosis drugs (i.e., isoniazid or rifampin) yet susceptible to ethionamide, ethionamide should be accompanied by at least one drug to which the M. tuberculosis isolate is known to be susceptible.3 If the tuberculosis is resistant to both isoniazid and rifampin, yet susceptible to ethionamide, ethionamide should be accompanied by at least two other drugs to which the M. tuberculosis isolate is known to be susceptible.3 Patient nonadherence to prescribed treatment can result in treatment failure and in the development of drug-resistant tuberculosis, which can be life-threatening and lead to other serious health risks. It is, therefore, essential that patients adhere to the drug regimen for the full duration of treatment. Directly observed therapy is recommended for all patients receiving treatment for tuberculosis. Patients in whom drug-resistant M. tuberculosis organisms are isolated should be managed in consultation with an expert in the treatment of drug-resistant tuberculosis. Launch Date 1965

C_max

Value	Dose	Co-administered	Analyte	Population
2.16 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/013026s024lbl.pdf	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:		ETHIONAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
7.67 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/013026s024lbl.pdf	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:		ETHIONAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.92 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/013026s024lbl.pdf	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:		ETHIONAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
70% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/013026s024lbl.pdf	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:		ETHIONAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

Doses

Dose	Population	Adverse events
0.1 g 2 times / week multiple, oral MTD Dose: 0.1 g, 2 times / week Route: oral Route: multiple Dose: 0.1 g, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/4924649/	unhealthy, >12 Health Status: unhealthy Age Group: >12 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/4924649/	Sources: https://pubmed.ncbi.nlm.nih.gov/4924649/
0.5 g 2 times / week multiple, oral MTD Dose: 0.5 g, 2 times / week Route: oral Route: multiple Dose: 0.5 g, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/4924649/	unhealthy, >12 Health Status: unhealthy Age Group: >12 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/4924649/	Sources: https://pubmed.ncbi.nlm.nih.gov/4924649/
0.75 g 2 times / week multiple, oral MTD Dose: 0.75 g, 2 times / week Route: oral Route: multiple Dose: 0.75 g, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/4924649/	unhealthy, >12 Health Status: unhealthy Age Group: >12 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/4924649/	Sources: https://pubmed.ncbi.nlm.nih.gov/4924649/
1.25 g 2 times / week multiple, oral MTD Dose: 1.25 g, 2 times / week Route: oral Route: multiple Dose: 1.25 g, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/4924649/	unhealthy, >12 Health Status: unhealthy Age Group: >12 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/4924649/	Sources: https://pubmed.ncbi.nlm.nih.gov/4924649/
1.5 g 2 times / week multiple, oral MTD Dose: 1.5 g, 2 times / week Route: oral Route: multiple Dose: 1.5 g, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/4924649/	unhealthy, >12 Health Status: unhealthy Age Group: >12 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/4924649/	Sources: https://pubmed.ncbi.nlm.nih.gov/4924649/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 CYP2B6 926 CYP2C8 1057 CYP2C19 2057 BCRP 910 OATP1B1 1079

Drug as perpetrator

Target	Modality	Activity
CYP2C9 2497	inhibitor 4027 Sources: https://www.jstage.jst.go.jp/article/bpb/38/9/38_b15-00313/_pdf/-char/en#page=4 Page: 4.0	no
CYP2D6 2546	inhibitor 4027 Sources: https://www.jstage.jst.go.jp/article/bpb/38/9/38_b15-00313/_pdf/-char/en#page=4 Page: 4.0	no
OATP1B1 1095	inhibitor 4027 Sources: https://web.archive.org/web/20210121185751/https://www.natap.org/2020/GLASGOW/GLASGOW_66.htm	weak
CYP2C8 1117	inhibitor 4027 Sources: https://www.jstage.jst.go.jp/article/bpb/38/9/38_b15-00313/_pdf/-char/en#page=4 Page: 4.0	yes [IC50 110 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.jstage.jst.go.jp/article/bpb/38/9/38_b15-00313/_pdf/-char/en#page=4 Page: 4.0	yes [IC50 195 uM]
CYP2B6 1160	inhibitor 4027 Sources: https://www.jstage.jst.go.jp/article/bpb/38/9/38_b15-00313/_pdf/-char/en#page=4 Page: 4.0	yes [IC50 396 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://www.jstage.jst.go.jp/article/bpb/38/9/38_b15-00313/_pdf/-char/en#page=4 Page: 4.0	yes [IC50 524 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4068461/	yes [IC50 78.4 uM]
BCRP 985	inhibitor 4027 Sources: https://web.archive.org/web/20210121185751/https://www.natap.org/2020/GLASGOW/GLASGOW_66.htm	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:4885	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:4885
ChemicalBook	CB1292374	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB1292374
eMolecules	538116	https://www.emolecules.com/cgi-bin/more?vid=538116
MolPort	MolPort-000-159-777	https://www.molport.com/shop/molecule-link/MolPort-000-159-777
Selleck Chemicals	Ethionamide	http://www.selleckchem.com/products/Ethionamide.html
ZINC	ZINC000003872520	http://zinc15.docking.org/substances/ZINC000003872520

PubMed

Title	Date	PubMed
Altered NADH/NAD+ ratio mediates coresistance to isoniazid and ethionamide in mycobacteria.	2005-02	15673755
Electron transfer kinetics and mechanistic study of the thionicotinamide coordinated to the pentacyanoferrate(III)/(II) complexes: a model system for the in vitro activation of thioamides anti-tuberculosis drugs.	2005-02	15621268
Analysis of Mycobacterium tuberculosis isolates from treatment failure patients living in East Timor.	2005-01	15675555
Drug susceptibility of Brazilian strains of Mycobacterium bovis using traditional and molecular techniques.	2004-11	15654433
Inhibitory effect of antituberculosis drugs on human cytochrome P450-mediated activities.	2004-11	15528841
Polymorphism and solvolysis of 2-cyano-3-[4-(N,N-diethylamino)phenyl]prop-2-enethioamide.	2004-11	15528819
Axially dissymmetric N-thioacylated (S)-(-)-1,1'-binaphthyl-2,2'-diamine ligands for copper-catalyzed asymmetric Michael addition of diethylzinc to alpha,beta-unsaturated ketone.	2004-11	15455445
Adjuvant interferon gamma in patients with drug - resistant pulmonary tuberculosis: a pilot study.	2004-10-22	15500691
Structure of EthR in a ligand bound conformation reveals therapeutic perspectives against tuberculosis.	2004-10-22	15494316
Mycobacterium triplex pulmonary disease in immunocompetent host.	2004-10	15504279
Multidrug resistant miliary tuberculosis and Pott's disease in an immunocompetent patient.	2004-10	15494824
Outcome of treatment of multidrug resistant tuberculosis.	2004-09	15524226
Effect of glutathione on the covalent binding of the 13C-labeled skin sensitizer 5-chloro-2-methylisothiazol-3-one to human serum albumin: identification of adducts by nuclear magnetic resonance, matrix-assisted laser desorption/ionization mass spectrometry, and nanoelectrospray tandem mass spectrometry.	2004-09	15377163
Pyridylthiocarbazide complexes of rhenium with potential radiopharmaceutical applications.	2004-08-21	15303150
Antituberculous activity of some aryl semicarbazone derivatives.	2004-08-02	15225698
Synthesis and antibacterial activity of arylpiperazinyl oxazolidinones with diversification of the N-substituents.	2004-08-02	15225689
Pharmacy data for tuberculosis surveillance and assessment of patient management.	2004-08	15496244
Crystal structure of the TetR/CamR family repressor Mycobacterium tuberculosis EthR implicated in ethionamide resistance.	2004-07-23	15236969
Treatment and follow-up of HIV-negative multidrug-resistant tuberculosis patients in an infectious diseases reference hospital, Buenos Aires, Argentina.	2004-06	15182150
Surveillance of Mycobacterium tuberculosis susceptibility to second-line drugs in Hong Kong, 1995-2002, after the implementation of DOTS-plus.	2004-06	15182147
Iatrogenic Mycobacterium simiae skin infection in an immunocompetent patient.	2004-05	15216858
Synthesis and antimycobacterial activity of 1,2,4-triazole 3-benzylsulfanyl derivatives.	2004-04	15081345
Use of MGIT 960 for rapid quantitative measurement of the susceptibility of Mycobacterium tuberculosis complex to ciprofloxacin and ethionamide.	2004-04	14973155
A case study in Hansen's disease acquired after heart transplant.	2004-02-21	14974527
A microplate indicator-based method for determining the susceptibility of multidrug-resistant Mycobacterium tuberculosis to antimicrobial agents.	2004-02	15139456
Computational study of conformational preferences of thioamide-containing azaglycine peptides.	2004-01-30	14648616
The prodrug activator EtaA from Mycobacterium tuberculosis is a Baeyer-Villiger monooxygenase.	2004-01-30	14610090
Covalent binding of the 13C-labeled skin sensitizers 5-chloro-2-methylisothiazol-3-one (MCI) and 2-methylisothiazol-3-one (MI) to a model peptide and glutathione.	2004-01-19	14698160
EthR, a repressor of the TetR/CamR family implicated in ethionamide resistance in mycobacteria, octamerizes cooperatively on its operator.	2004-01	14651620
New agents active against Mycobacterium avium complex selected by molecular topology: a virtual screening method.	2004-01	14645324
Pharmacokinetics and relative bioavailability of clofazimine in relation to food, orange juice and antacid.	2004	15525560
Kinetic spectrophotometric determination of some sulfur containing compounds in pharmaceutical preparations and human serum.	2003-12	14630247
Lepromatous leprosy in a heart transplant recipient.	2003-12	14629293
Invasive Mycobacterium marinum infections.	2003-11	14725262
Reaction and characterization of thioamide dianions derived from N-benzyl thioamides.	2003-10-31	14575479
Evaluation of indirect susceptibility testing of Mycobacterium tuberculosis to the first- and second-line, and alternative drugs by the newer MB/BacT system.	2003-09	14595463
Incorporation of antibiotics in liposomes designed for tuberculosis therapy by inhalation.	2003-08-29	12944141
Gatifloxacin and ethionamide as the foundation for therapy of tuberculosis.	2003-08	12878502
Chronic cases of tuberculosis in Casablanca, Morocco.	2003-07	12870687
Inhibition of InhA activity, but not KasA activity, induces formation of a KasA-containing complex in mycobacteria.	2003-06-06	12654922
Inactivation of mshB, a key gene in the mycothiol biosynthesis pathway in Mycobacterium smegmatis.	2003-05	12724395
Vibrational study of the secondary thioamide function, the intramolecular resonance assisted and intermolecular hydrogen bonding in NN'-hydroxyalkyl dithiooxamides.	2003-04	12659905
Preparation of thioamide building blocks via microwave-promoted three-component kindler reactions.	2003-03-11	12625704
Vibrational characterization of the tertiary amide and thioamide group.	2003-03-01	12609634
Mycobacterium celatum pulmonary infection in the immunocompetent: case report and review.	2003-03	12643843
Multidrug-resistant tuberculosis in pregnancy: case report and review of the literature.	2003-03	12628902
The 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay as rapid colorimetric method for determination of antibiotic susceptibility of clinical Mycobacterium tuberculosis isolates in liquid medium.	2003	12908735
Spectrum of drugs against atypical mycobacteria: how valid is the current practice of drug susceptibility testing and the choice of drugs?	1992-12	1303690
Mycolic acid synthesis: a target for ethionamide in mycobacteria?	1992-06	1416831
The antituberculous activity of thioamide in vitro and in the experimental animal (mouse and guinea pig).	1960-05	13833984

Patents

Sample Use Guides

In Vivo Use Guide

15 to 20 mg/kg/day, administered once daily

Route of Administration: Oral

In Vitro Use Guide

Two standardized in vitro susceptibility methods are available for testing ethionamide against M. tuberculosis organisms. The modified proportion method (CDC or NCCLS M24-P) utilizes Middlebrook and Cohn 7H10 agar medium impregnated with ethionamide at a final concentration of 5.0 ug/mL. After 2 to 3 weeks of incubation, MIC99 values are calculated by comparing the quantity of organisms growing in the medium containing drug to the control cultures. Mycobacterial growth in the presence of drug, of at least 1% of the growth in the control culture, indicates resistance.

Substance Class	Chemical Created by `admin` on `Wed Apr 02 07:43:03 GMT 2025` Edited by `admin` on `Wed Apr 02 07:43:03 GMT 2025`
Record UNII	OAY8ORS3CQ
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ETHIONAMIDE

Official Name

English

TRECATOR-SC

Preferred Name

English

ETHIONAMIDE [VANDF]

Common Name

English

ethionamide [INN]

Common Name

English

ETHIONAMIDE [HSDB]

Common Name

English

ETHIONAMIDE [IARC]

Common Name

English

ETHIONAMIDE [MI]

Common Name

English

ETHIONAMIDE [EP MONOGRAPH]

Common Name

English

ETHIONAMIDE [ORANGE BOOK]

Common Name

English

TRECATOR

Brand Name

English

ETHIONAMIDE [JAN]

Common Name

English

ETHIONAMIDE [USAN]

Common Name

English

1314-TH

Code

English

4-PYRIDINECARBOTHIOAMIDE, 2-ETHYL-

Systematic Name

English

1314 TH

Code

English

ETHIONAMIDE [USP MONOGRAPH]

Common Name

English

ETHIONAMIDUM [WHO-IP LATIN]

Common Name

English

BAYER 5312

Code

English

2-Ethylthioisonicotinamide

Systematic Name

English

ETHIONAMIDE [USP-RS]

Common Name

English

Ethionamide [WHO-DD]

Common Name

English

ETHIONAMIDE [MART.]

Common Name

English

ETHIONAMIDE [WHO-IP]

Common Name

English

NSC-255115

Code

English

NIZOTIN

Common Name

English

Classification Tree Code System Code

WHO-VATC

QJ04AD03