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

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 of ETHIONAMIDE

SMILES

CCC1=NC=CC(=C1)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
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,

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P9WIE5|||Q50553
Gene ID: 885638.0
Gene Symbol: katG
Target Organism: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
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
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
2.16 μg/mL
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

AUC

ValueDoseCo-administeredAnalytePopulation
7.67 μg × h/mL
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
1.92 h
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
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
70%
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

Doses

DosePopulationAdverse 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
Co-administed with::
AMINOSALICYLATE SODIUM(6 g; oral; 2/week)
ISONIAZID(15 mg/kg; oral; 2/week)
Sources:
unhealthy, >12
n = 27
Health Status: unhealthy
Condition: pulmonary tuberculosis
Age Group: >12
Sex: M+F
Population Size: 27
Sources:
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
Co-administed with::
AMINOSALICYLATE SODIUM(6 g; oral; 2/week)
ISONIAZID(15 mg/kg; oral; 2/week)
Sources:
unhealthy, >12
n = 27
Health Status: unhealthy
Condition: pulmonary tuberculosis
Age Group: >12
Sex: M+F
Population Size: 27
Sources:
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
Co-administed with::
AMINOSALICYLATE SODIUM(6 g; oral; 2/week)
ISONIAZID(15 mg/kg; oral; 2/week)
Sources:
unhealthy, >12
n = 27
Health Status: unhealthy
Condition: pulmonary tuberculosis
Age Group: >12
Sex: M+F
Population Size: 27
Sources:
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
Co-administed with::
AMINOSALICYLATE SODIUM(6 g; oral; 2/week)
ISONIAZID(15 mg/kg; oral; 2/week)
Sources:
unhealthy, >12
n = 27
Health Status: unhealthy
Condition: pulmonary tuberculosis
Age Group: >12
Sex: M+F
Population Size: 27
Sources:
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
Co-administed with::
AMINOSALICYLATE SODIUM(6 g; oral; 2/week)
ISONIAZID(15 mg/kg; oral; 2/week)
Sources:
unhealthy, >12
n = 27
Health Status: unhealthy
Condition: pulmonary tuberculosis
Age Group: >12
Sex: M+F
Population Size: 27
Sources:
PubMed

PubMed

TitleDatePubMed
Spectrum of drugs against atypical mycobacteria: how valid is the current practice of drug susceptibility testing and the choice of drugs?
1992 Dec
Mycolic acid synthesis: a target for ethionamide in mycobacteria?
1992 Jun
Ethionamide activation and sensitivity in multidrug-resistant Mycobacterium tuberculosis.
2000 Aug 15
Activation of the pro-drug ethionamide is regulated in mycobacteria.
2000 Sep 8
Conformational analysis of thiopeptides: free energy calculations on the effects of thio-substitutions on the conformational distributions of alanine dipeptides.
2001
Synthesis of 3'-thioamido-modified 3'-deoxythymidine-5'-triphosphates and their use as chain terminators in Sanger-DNA sequencing.
2001 Apr-Jul
Efficacy and safety of sparfloxacin in combination with kanamycin and ethionamide in multidrug-resistant pulmonary tuberculosis patients: preliminary results.
2001 Jun
Solvent effects on the thioamide rotational barrier: an experimental and theoretical study.
2001 Mar 7
Pharmacokinetics of para-aminosalicylic acid granules under four dosing conditions.
2001 Nov
[Two cases of multi-drug-resistant pulmonary tuberculosis with para-aminosalicylic acid (PAS)-induced hypothyroidism].
2001 Oct
Comparative study on the use of solid media: Löwenstein-Jensen and Ogawa in the determination of anti-tuberculosis drug susceptibility.
2002
[Multicenter evaluation of a newly developed microdilution test, brothMIC NTM to determine minimum inhibitory concentrations of antimicrobial agents for nontuberculous mycobacteria].
2002 Apr
Structure-activity relationships for a series of thiobenzamide influenza fusion inhibitors derived from 1,3,3-trimethyl-5-hydroxy-cyclohexylmethylamine.
2002 Dec 2
Monothioacids as novel chelating groups. The Au(III) complexes of N-methylthioamide monothiooxamic acid.
2002 Jun
Direct sensitivity test of the MB/BacT system.
2002 Mar
Overexpression of inhA, but not kasA, confers resistance to isoniazid and ethionamide in Mycobacterium smegmatis, M. bovis BCG and M. tuberculosis.
2002 Oct
Prevalence of acquired MDR-TB and HIV co-infection.
2002 Oct-Dec
Vibrational study of the secondary thioamide function, the intramolecular resonance assisted and intermolecular hydrogen bonding in NN'-hydroxyalkyl dithiooxamides.
2003 Apr
Gatifloxacin and ethionamide as the foundation for therapy of tuberculosis.
2003 Aug
Kinetic spectrophotometric determination of some sulfur containing compounds in pharmaceutical preparations and human serum.
2003 Dec
Preparation of thioamide building blocks via microwave-promoted three-component kindler reactions.
2003 Mar-Apr
Inactivation of mshB, a key gene in the mycothiol biosynthesis pathway in Mycobacterium smegmatis.
2003 May
Invasive Mycobacterium marinum infections.
2003 Nov
Reaction and characterization of thioamide dianions derived from N-benzyl thioamides.
2003 Oct 31
Synthesis and antimycobacterial activity of 1,2,4-triazole 3-benzylsulfanyl derivatives.
2004 Apr
Use of MGIT 960 for rapid quantitative measurement of the susceptibility of Mycobacterium tuberculosis complex to ciprofloxacin and ethionamide.
2004 Apr
Antituberculous activity of some aryl semicarbazone derivatives.
2004 Aug 2
Synthesis and antibacterial activity of arylpiperazinyl oxazolidinones with diversification of the N-substituents.
2004 Aug 2
Pyridylthiocarbazide complexes of rhenium with potential radiopharmaceutical applications.
2004 Aug 21
A microplate indicator-based method for determining the susceptibility of multidrug-resistant Mycobacterium tuberculosis to antimicrobial agents.
2004 Feb
EthR, a repressor of the TetR/CamR family implicated in ethionamide resistance in mycobacteria, octamerizes cooperatively on its operator.
2004 Jan
New agents active against Mycobacterium avium complex selected by molecular topology: a virtual screening method.
2004 Jan
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 Jan 19
Computational study of conformational preferences of thioamide-containing azaglycine peptides.
2004 Jan 30
A case study in Hansen's disease acquired after heart transplant.
2004 Jan-Mar
Crystal structure of the TetR/CamR family repressor Mycobacterium tuberculosis EthR implicated in ethionamide resistance.
2004 Jul 23
Treatment and follow-up of HIV-negative multidrug-resistant tuberculosis patients in an infectious diseases reference hospital, Buenos Aires, Argentina.
2004 Jun
Surveillance of Mycobacterium tuberculosis susceptibility to second-line drugs in Hong Kong, 1995-2002, after the implementation of DOTS-plus.
2004 Jun
Iatrogenic Mycobacterium simiae skin infection in an immunocompetent patient.
2004 May
Inhibitory effect of antituberculosis drugs on human cytochrome P450-mediated activities.
2004 Nov
Adjuvant interferon gamma in patients with drug - resistant pulmonary tuberculosis: a pilot study.
2004 Oct 22
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 Feb
Analysis of Mycobacterium tuberculosis isolates from treatment failure patients living in East Timor.
2005 Jan
Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment: If patient exhibits poor gastrointestinal tolerance, TRECATOR has to be administered in divided doses, with a maximum daily dosage of 1 gram
15 to 20 mg/kg/day, administered once daily
Route of Administration: Oral
In Vitro Use Guide
Curator's Comment: Standardized in vitro susceptibility method for testing ethionamide against M. tuberculosis organisms: after 2 to 3 weeks of incubation, MIC99 values are calculated.
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 Sat Dec 16 16:20:07 GMT 2023
Edited
by admin
on Sat Dec 16 16:20:07 GMT 2023
Record UNII
OAY8ORS3CQ
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ETHIONAMIDE
EP   HSDB   INN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD   WHO-IP  
INN   USAN  
Official 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
TRECATOR-SC
Brand Name 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
Created by admin on Sat Dec 16 16:20:09 GMT 2023 , Edited by admin on Sat Dec 16 16:20:09 GMT 2023
WHO-ESSENTIAL MEDICINES LIST 6.2.4
Created by admin on Sat Dec 16 16:20:09 GMT 2023 , Edited by admin on Sat Dec 16 16:20:09 GMT 2023
LIVERTOX NBK548025
Created by admin on Sat Dec 16 16:20:09 GMT 2023 , Edited by admin on Sat Dec 16 16:20:09 GMT 2023
NDF-RT N0000175483
Created by admin on Sat Dec 16 16:20:09 GMT 2023 , Edited by admin on Sat Dec 16 16:20:09 GMT 2023
NCI_THESAURUS C280
Created by admin on Sat Dec 16 16:20:09 GMT 2023 , Edited by admin on Sat Dec 16 16:20:09 GMT 2023
WHO-ATC J04AD03
Created by admin on Sat Dec 16 16:20:09 GMT 2023 , Edited by admin on Sat Dec 16 16:20:09 GMT 2023
Code System Code Type Description
FDA UNII
OAY8ORS3CQ
Created by admin on Sat Dec 16 16:20:09 GMT 2023 , Edited by admin on Sat Dec 16 16:20:09 GMT 2023
PRIMARY
SMS_ID
100000082598
Created by admin on Sat Dec 16 16:20:09 GMT 2023 , Edited by admin on Sat Dec 16 16:20:09 GMT 2023
PRIMARY
EPA CompTox
DTXSID0020577
Created by admin on Sat Dec 16 16:20:09 GMT 2023 , Edited by admin on Sat Dec 16 16:20:09 GMT 2023
PRIMARY
ChEMBL
CHEMBL1441
Created by admin on Sat Dec 16 16:20:09 GMT 2023 , Edited by admin on Sat Dec 16 16:20:09 GMT 2023
PRIMARY
NSC
255115
Created by admin on Sat Dec 16 16:20:09 GMT 2023 , Edited by admin on Sat Dec 16 16:20:09 GMT 2023
PRIMARY
RS_ITEM_NUM
1261004
Created by admin on Sat Dec 16 16:20:09 GMT 2023 , Edited by admin on Sat Dec 16 16:20:09 GMT 2023
PRIMARY
LACTMED
Ethionamide
Created by admin on Sat Dec 16 16:20:09 GMT 2023 , Edited by admin on Sat Dec 16 16:20:09 GMT 2023
PRIMARY
MESH
D005000
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PRIMARY
DRUG BANK
DB00609
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PRIMARY
EVMPD
SUB07278MIG
Created by admin on Sat Dec 16 16:20:09 GMT 2023 , Edited by admin on Sat Dec 16 16:20:09 GMT 2023
PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
ETHIONAMIDE
Created by admin on Sat Dec 16 16:20:09 GMT 2023 , Edited by admin on Sat Dec 16 16:20:09 GMT 2023
PRIMARY Description: Small yellow crystals or a yellow, crystalline powder; odour, slight.Solubility: Practically insoluble in water; soluble in methanol R; sparingly soluble in ethanol (~750 g/l) TS; slightly soluble in ether R.Category: Antileprosy drug.Storage: Ethionamide should be kept in a tightly closed container.Additional information: Ethionamide darkens on exposure to light.Definition: Ethionamide contains not less than 98.0% and not more than 101.0% of C8H10N2S, calculated with reference to the dried substance.
CAS
536-33-4
Created by admin on Sat Dec 16 16:20:09 GMT 2023 , Edited by admin on Sat Dec 16 16:20:09 GMT 2023
PRIMARY
DRUG CENTRAL
1083
Created by admin on Sat Dec 16 16:20:09 GMT 2023 , Edited by admin on Sat Dec 16 16:20:09 GMT 2023
PRIMARY
PUBCHEM
2761171
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PRIMARY
NCI_THESAURUS
C47522
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PRIMARY
MERCK INDEX
m5061
Created by admin on Sat Dec 16 16:20:09 GMT 2023 , Edited by admin on Sat Dec 16 16:20:09 GMT 2023
PRIMARY Merck Index
WIKIPEDIA
ETHIONAMIDE
Created by admin on Sat Dec 16 16:20:09 GMT 2023 , Edited by admin on Sat Dec 16 16:20:09 GMT 2023
PRIMARY
HSDB
7473
Created by admin on Sat Dec 16 16:20:09 GMT 2023 , Edited by admin on Sat Dec 16 16:20:09 GMT 2023
PRIMARY
ECHA (EC/EINECS)
208-628-9
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PRIMARY
INN
867
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PRIMARY
RXCUI
4127
Created by admin on Sat Dec 16 16:20:09 GMT 2023 , Edited by admin on Sat Dec 16 16:20:09 GMT 2023
PRIMARY RxNorm
CHEBI
4885
Created by admin on Sat Dec 16 16:20:09 GMT 2023 , Edited by admin on Sat Dec 16 16:20:09 GMT 2023
PRIMARY
DAILYMED
OAY8ORS3CQ
Created by admin on Sat Dec 16 16:20:09 GMT 2023 , Edited by admin on Sat Dec 16 16:20:09 GMT 2023
PRIMARY
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