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
The antituberculous activity of thioamide in vitro and in the experimental animal (mouse and guinea pig).	1960 May	13833984
Spectrum of drugs against atypical mycobacteria: how valid is the current practice of drug susceptibility testing and the choice of drugs?	1992 Dec	1303690
Mycolic acid synthesis: a target for ethionamide in mycobacteria?	1992 Jun	1416831
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
Conformational analysis of thiopeptides: free energy calculations on the effects of thio-substitutions on the conformational distributions of alanine dipeptides.	2001	11766049
The molecular basis of resistance to isoniazid, rifampin, and pyrazinamide in Mycobacterium tuberculosis.	2001	11686881
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
Pharmacokinetics of cycloserine under fasting conditions and with high-fat meal, orange juice, and antacids.	2001 Aug	11718495
[Multicenter evaluation of a newly developed microdilution test, brothMIC NTM to determine minimum inhibitory concentrations of antimicrobial agents for nontuberculous mycobacteria].	2002 Apr	12014018
Inhibition of testosterone production by propylthiouracil in rat Leydig cells.	2002 Aug	12135875
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
[Medication-induced hepatic lesions in patients with pulmonary tuberculosis].	2002 May	12073843
Drugs that inhibit mycolic acid biosynthesis in Mycobacterium tuberculosis.	2002 Sep	12164478
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
Kinetic spectrophotometric determination of some sulfur containing compounds in pharmaceutical preparations and human serum.	2003 Dec	14630247
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
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
Use of MGIT 960 for rapid quantitative measurement of the susceptibility of Mycobacterium tuberculosis complex to ciprofloxacin and ethionamide.	2004 Apr	14973155
Synthesis and antibacterial activity of arylpiperazinyl oxazolidinones with diversification of the N-substituents.	2004 Aug 2	15225689
EthR, a repressor of the TetR/CamR family implicated in ethionamide resistance in mycobacteria, octamerizes cooperatively on its operator.	2004 Jan	14651620
The prodrug activator EtaA from Mycobacterium tuberculosis is a Baeyer-Villiger monooxygenase.	2004 Jan 30	14610090
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
Inhibitory effect of antituberculosis drugs on human cytochrome P450-mediated activities.	2004 Nov	15528841
Multidrug resistant miliary tuberculosis and Pott's disease in an immunocompetent patient.	2004 Oct	15494824
Structure of EthR in a ligand bound conformation reveals therapeutic perspectives against tuberculosis.	2004 Oct 22	15494316
Altered NADH/NAD+ ratio mediates coresistance to isoniazid and ethionamide in mycobacteria.	2005 Feb	15673755
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