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 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 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Tuberculosis 83 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2006/013026s024lbl.pdf	Curative		Approved 8429	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 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 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2B6 810 CYP2C8 911 CYP2C19 1478 BCRP 699 OATP1B1 788

Drug as perpetrator

Target	Modality	Activity
CYP2C9 1819	inhibitor 3277 Sources: https://www.jstage.jst.go.jp/article/bpb/38/9/38_b15-00313/_pdf/-char/en#page=4 Page: 4.0	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.jstage.jst.go.jp/article/bpb/38/9/38_b15-00313/_pdf/-char/en#page=4 Page: 4.0	no
OATP1B1 803	inhibitor 3277 Sources: https://web.archive.org/web/20210121185751/https://www.natap.org/2020/GLASGOW/GLASGOW_66.htm	weak
CYP2C8 965	inhibitor 3277 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 1553	inhibitor 3277 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 1001	inhibitor 3277 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 1692	inhibitor 3277 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 1925	inhibitor 3277 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4068461/	yes [IC50 78.4 uM]
BCRP 773	inhibitor 3277 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
Mycolic acid synthesis: a target for ethionamide in mycobacteria?	1992 Jun	1416831
Ethionamide activation and sensitivity in multidrug-resistant Mycobacterium tuberculosis.	2000 Aug 15	10944230
Use of genomics and combinatorial chemistry in the development of new antimycobacterial drugs.	2000 Feb 1	10609550
Thiolactomycin and related analogues as novel anti-mycobacterial agents targeting KasA and KasB condensing enzymes in Mycobacterium tuberculosis.	2000 Jun 2	10747933
Activation of the pro-drug ethionamide is regulated in mycobacteria.	2000 Sep 8	10869356
Conformational analysis of thiopeptides: free energy calculations on the effects of thio-substitutions on the conformational distributions of alanine dipeptides.	2001	11766049
[Components of monitoring drug resistance of tuberculosis agent in the evaluation of effectiveness of the national tuberculosis control program].	2001	11490457
Ion interaction reagent reversed-phase high-performance liquid chromatography determination of anti-tuberculosis drugs and metabolites in biological fluids.	2001 Apr 25	11339291
High-performance liquid chromatographic-tandem mass spectrometric method for the determination of ethionamide in human plasma, bronchoalveolar lavage fluid and alveolar cells.	2001 Apr 5	11334350
Synthesis of 3'-thioamido-modified 3'-deoxythymidine-5'-triphosphates and their use as chain terminators in Sanger-DNA sequencing.	2001 Apr-Jul	11563136
Carbon-carbon-linked (pyrazolylphenyl)oxazolidinones with antibacterial activity against multiple drug resistant gram-positive and fastidious gram-negative bacteria.	2001 Dec	11711300
Efficacy and safety of sparfloxacin in combination with kanamycin and ethionamide in multidrug-resistant pulmonary tuberculosis patients: preliminary results.	2001 Jun	11409584
Compatibility of the thioamide functional group with beta-sheet secondary structure: incorporation of a thioamide linkage into a beta-hairpin peptide.	2001 Oct 18	11594837
Toxicity assessment of 255 chemicals to pure cultured nitrifying bacteria using biosensor.	2002	12523774
Comparative study on the use of solid media: Löwenstein-Jensen and Ogawa in the determination of anti-tuberculosis drug susceptibility.	2002	12356456
High-pressure Fourier transform micro-Raman spectroscopic investigation of diiodine-heterocyclic thioamide adducts.	2002 Oct	12396055
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
Chronic cases of tuberculosis in Casablanca, Morocco.	2003 Jul	12870687
Mycobacterium celatum pulmonary infection in the immunocompetent: case report and review.	2003 Mar	12643843
Evaluation of indirect susceptibility testing of Mycobacterium tuberculosis to the first- and second-line, and alternative drugs by the newer MB/BacT system.	2003 Sep	14595463
The prodrug activator EtaA from Mycobacterium tuberculosis is a Baeyer-Villiger monooxygenase.	2004 Jan 30	14610090
Crystal structure of the TetR/CamR family repressor Mycobacterium tuberculosis EthR implicated in ethionamide resistance.	2004 Jul 23	15236969
Surveillance of Mycobacterium tuberculosis susceptibility to second-line drugs in Hong Kong, 1995-2002, after the implementation of DOTS-plus.	2004 Jun	15182147
Altered NADH/NAD+ ratio mediates coresistance to isoniazid and ethionamide in mycobacteria.	2005 Feb	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 Feb	15621268
Analysis of Mycobacterium tuberculosis isolates from treatment failure patients living in East Timor.	2005 Jan	15675555

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 `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

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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