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=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
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 2 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 656
Enoyl-[acyl-carrier-protein] reductase 4 Target ID: CHEMBL1849 Sources: http://www.ncbi.nlm.nih.gov/pubmed/10944230	Inhibitor 8228

Conditions

Condition	Modality	Targets	Highest Phase	Product
Tuberculosis 81 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2006/013026s024lbl.pdf	Curative		Approved 8360	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 -1.47484803E11

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 Co-administed with:: AMINOSALICYLATE SODIUM(6 g; oral; 2/week) ISONIAZID(15 mg/kg; oral; 2/week) Sources: https://pubmed.ncbi.nlm.nih.gov/4924649/	unhealthy, >12 n = 27 Health Status: unhealthy Condition: pulmonary tuberculosis Age Group: >12 Sex: M+F Population Size: 27 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 Co-administed with:: AMINOSALICYLATE SODIUM(6 g; oral; 2/week) ISONIAZID(15 mg/kg; oral; 2/week) Sources: https://pubmed.ncbi.nlm.nih.gov/4924649/	unhealthy, >12 n = 27 Health Status: unhealthy Condition: pulmonary tuberculosis Age Group: >12 Sex: M+F Population Size: 27 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 Co-administed with:: AMINOSALICYLATE SODIUM(6 g; oral; 2/week) ISONIAZID(15 mg/kg; oral; 2/week) Sources: https://pubmed.ncbi.nlm.nih.gov/4924649/	unhealthy, >12 n = 27 Health Status: unhealthy Condition: pulmonary tuberculosis Age Group: >12 Sex: M+F Population Size: 27 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 Co-administed with:: AMINOSALICYLATE SODIUM(6 g; oral; 2/week) ISONIAZID(15 mg/kg; oral; 2/week) Sources: https://pubmed.ncbi.nlm.nih.gov/4924649/	unhealthy, >12 n = 27 Health Status: unhealthy Condition: pulmonary tuberculosis Age Group: >12 Sex: M+F Population Size: 27 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 Co-administed with:: AMINOSALICYLATE SODIUM(6 g; oral; 2/week) ISONIAZID(15 mg/kg; oral; 2/week) Sources: https://pubmed.ncbi.nlm.nih.gov/4924649/	unhealthy, >12 n = 27 Health Status: unhealthy Condition: pulmonary tuberculosis Age Group: >12 Sex: M+F Population Size: 27 Sources: https://pubmed.ncbi.nlm.nih.gov/4924649/	Sources: https://pubmed.ncbi.nlm.nih.gov/4924649/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1579	inhibitor 1752	inhibitor 1837

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1509 CYP2B6 799 CYP2C8 901 CYP2C19 1463 BCRP 691 OATP1B1 781

Drug as perpetrator

Target	Modality	Activity
CYP2C9 1803	inhibitor 3240 Sources: https://www.jstage.jst.go.jp/article/bpb/38/9/38_b15-00313/_pdf/-char/en#page=4 Page: 4.0	no
CYP2D6 1875	inhibitor 3240 Sources: https://www.jstage.jst.go.jp/article/bpb/38/9/38_b15-00313/_pdf/-char/en#page=4 Page: 4.0	no
OATP1B1 796	inhibitor 3240 Sources: https://web.archive.org/web/20210121185751/https://www.natap.org/2020/GLASGOW/GLASGOW_66.htm	weak
CYP2C8 955	inhibitor 3240 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 1537	inhibitor 3240 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 985	inhibitor 3240 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 1673	inhibitor 3240 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 1909	inhibitor 3240 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4068461/	yes [IC50 78.4 uM]
BCRP 765	inhibitor 3240 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
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
eMolecules	538116	https://www.emolecules.com/cgi-bin/more?vid=538116

PubMed

Title	Date	PubMed
The antituberculous activity of thioamide in vitro and in the experimental animal (mouse and guinea pig).	1960 May	13833984
Mycolic acid synthesis: a target for ethionamide in mycobacteria?	1992 Jun	1416831
[Treatment outcomes of multidrug-resistant tuberculosis--comparison between success and failure cases].	2001 Dec	11806128
Synthesis and cytotoxicity of bis(benzo[g]indole-3-carboxamides) and related compounds.	2001 Nov	11822170
Therapeutic drug monitoring in the treatment of tuberculosis.	2002	12381217
Comparative study on the use of solid media: Löwenstein-Jensen and Ogawa in the determination of anti-tuberculosis drug susceptibility.	2002	12356456
[Multicenter evaluation of a newly developed microdilution test, brothMIC NTM to determine minimum inhibitory concentrations of antimicrobial agents for nontuberculous mycobacteria].	2002 Apr	12014018
The antituberculosis drug ethionamide is activated by a flavoprotein monooxygenase.	2002 Apr 12	11823459
Inhibition of testosterone production by propylthiouracil in rat Leydig cells.	2002 Aug	12135875
2-Pyridinethiol/2-pyridinethione tautomeric equilibrium. A comparative experimental and computational study.	2002 Dec 13	12467429
Structure-activity relationships for a series of thiobenzamide influenza fusion inhibitors derived from 1,3,3-trimethyl-5-hydroxy-cyclohexylmethylamine.	2002 Dec 2	12419365
First use of axially chiral thioamides for the stereocontrol of C-C bond formation.	2002 Feb 2	11855710
Monothioacids as novel chelating groups. The Au(III) complexes of N-methylthioamide monothiooxamic acid.	2002 Jun	12166750
Transition metal complexes with thiosemicarbazide-based ligands. XLIII. Chlorobis(3-methylisoemicarbazide-kappa(2)N(1),N(4))zinc(II) chloride.	2002 Jun	12050422
Feasibility and cost-effectiveness of standardised second-line drug treatment for chronic tuberculosis patients: a national cohort study in Peru.	2002 Jun 8	12076553
Direct sensitivity test of the MB/BacT system.	2002 Mar	12016454
Effects of thioamide substitutions on the conformation and stability of alpha- and 3(10)-helices.	2002 May 8	11982387
Molecular epidemiology of multidrug-resistant tuberculosis, New York City, 1995-1997.	2002 Nov	12453347
Identifying the sources of tuberculosis in young children: a multistate investigation.	2002 Nov	12453345
Molecular epidemiology of tuberculosis in a sentinel surveillance population.	2002 Nov	12453343
Heterocyclic benzazole derivatives with antimycobacterial in vitro activity.	2002 Nov 18	12392731
Prevalence of acquired MDR-TB and HIV co-infection.	2002 Oct-Dec	12437236
Drugs that inhibit mycolic acid biosynthesis in Mycobacterium tuberculosis.	2002 Sep	12164478
Diversity in the oxidation of substrates by cytochrome P450 2D6: lack of an obligatory role of aspartate 301-substrate electrostatic bonding.	2002 Sep 10	12206675
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
Vibrational study of the secondary thioamide function, the intramolecular resonance assisted and intermolecular hydrogen bonding in NN'-hydroxyalkyl dithiooxamides.	2003 Apr	12659905
Gatifloxacin and ethionamide as the foundation for therapy of tuberculosis.	2003 Aug	12878502
Activities of moxifloxacin alone and in combination with other antimicrobial agents against multidrug-resistant Mycobacterium tuberculosis infection in BALB/c mice.	2003 Jan	12499213
Chronic cases of tuberculosis in Casablanca, Morocco.	2003 Jul	12870687
Incorporation of antibiotics in liposomes designed for tuberculosis therapy by inhalation.	2003 Jul-Sep	12944141
Inhibition of InhA activity, but not KasA activity, induces formation of a KasA-containing complex in mycobacteria.	2003 Jun 6	12654922
Mycobacterium celatum pulmonary infection in the immunocompetent: case report and review.	2003 Mar	12643843
Preparation of thioamide building blocks via microwave-promoted three-component kindler reactions.	2003 Mar-Apr	12625704
Synthesis and antimycobacterial activity of 1,2,4-triazole 3-benzylsulfanyl derivatives.	2004 Apr	15081345
Use of MGIT 960 for rapid quantitative measurement of the susceptibility of Mycobacterium tuberculosis complex to ciprofloxacin and ethionamide.	2004 Apr	14973155
Pharmacy data for tuberculosis surveillance and assessment of patient management.	2004 Aug	15496244
Antituberculous activity of some aryl semicarbazone derivatives.	2004 Aug 2	15225698
A microplate indicator-based method for determining the susceptibility of multidrug-resistant Mycobacterium tuberculosis to antimicrobial agents.	2004 Feb	15139456
EthR, a repressor of the TetR/CamR family implicated in ethionamide resistance in mycobacteria, octamerizes cooperatively on its operator.	2004 Jan	14651620
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	14698160
Computational study of conformational preferences of thioamide-containing azaglycine peptides.	2004 Jan 30	14648616
A case study in Hansen's disease acquired after heart transplant.	2004 Jan-Mar	14974527
Treatment and follow-up of HIV-negative multidrug-resistant tuberculosis patients in an infectious diseases reference hospital, Buenos Aires, Argentina.	2004 Jun	15182150
Surveillance of Mycobacterium tuberculosis susceptibility to second-line drugs in Hong Kong, 1995-2002, after the implementation of DOTS-plus.	2004 Jun	15182147
Drug susceptibility of Brazilian strains of Mycobacterium bovis using traditional and molecular techniques.	2004 Nov	15654433
Polymorphism and solvolysis of 2-cyano-3-[4-(N,N-diethylamino)phenyl]prop-2-enethioamide.	2004 Nov	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 Nov	15455445
Multidrug resistant miliary tuberculosis and Pott's disease in an immunocompetent patient.	2004 Oct	15494824
Adjuvant interferon gamma in patients with drug - resistant pulmonary tuberculosis: a pilot study.	2004 Oct 22	15500691
Structure of EthR in a ligand bound conformation reveals therapeutic perspectives against tuberculosis.	2004 Oct 22	15494316

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 `Thu Jul 06 21:50:13 UTC 2023` Edited by `admin` on `Thu Jul 06 21:50:13 UTC 2023`
Record UNII	OAY8ORS3CQ
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ETHIONAMIDE

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